M-1 PHARAMACEUTICS AND

PHARMACEUTICAL TECHNOLOGY
1.1 Introduction to pharmaceutics
Introduction
 The word ‘pharmaceutics’ is used in pharmacy and the pharmaceutical sciences to
encompass a wide range of subject areas that are all associated with the steps to which
a drug is subjected towards the end of its development.
 It encompasses the stages that follow on from the discovery or synthesis of the drug, its
isolation and purification, and its testing for beneficial pharmacological effects and
absence of serious toxicological problems. Put at its simplest – pharmaceutics converts
a drug into a medicine.
 It deals with the pharmaceutical dosage forms, Pharmaceuticals formulations,
Pharmaceutical manufacturing and quality control and Bio-pharmaceutics.

Defintion
 Pharmaceutics is the branch of Pharmacy deals with the overall process of developing
a new chemical entity into an approved therapy that is safe and effective in treating or
preventing disease.

Purpose of Pharmaceutics
 Ensures stability, bioavailability, and patient acceptability of medicines.
 Converts active pharmaceutical ingredients (APIs) into dosage forms like tablets,
capsules, injections, etc.

Scope of Pharmaceutics
 An understanding of the basic physical chemistry necessary for the effective design of
dosage forms (physical pharmaceutics).
 An understanding of relevant body systems and how drugs arrive there following
administration (biopharmaceutics).
 The design and formulation of medicines (dosage form design).
 The manufacture of these medicines on a small (compounding), intermediate (pilot-
scale) and large (manufacturing) scale.
 The avoidance and elimination of microorganisms in medicines (pharmaceutical
microbiology, sterilization).
 Product performance testing (physical testing, drug release, stability testing).
Branches of Pharmaceutics
 Pharmaceutical Formulation: This involves blending various chemical ingredients to
create the final medicinal product ready for use.

 Pharmaceutical Manufacturing: Refers to the large-scale industrial production of

pharmaceutical drugs carried out by pharmaceutical companies.
 Dispensing Pharmacy: Encompasses the practice of preparing and providing
prescribed medications. Pharmacy practice covers traditional tasks like compounding
and dispensing drugs, as well as modern patient-centered services such as clinical care,
medication safety reviews, and offering detailed drug information.
 Physical Pharmacy: Focuses on the study of the physical and chemical characteristics
of drugs, excipients, and solvents, and how these properties influence the design and
formulation of dosage forms. Key areas include micromeritics (particle size and
distribution), rheology (flow properties), and interfacial tension.
 Biopharmaceutics: Examines the biological processes affecting drugs within the body,
specifically their absorption, distribution, metabolism, and elimination (ADME).
 Pharmaceutical Jurisprudence: Covers the legal principles and regulations governing
pharmaceuticals, including the laws, schedules, and acts that shape the Indian
healthcare system.
 Microbiology: The study of microorganisms, their role in diseases, and the
development of antibiotics and other antimicrobial agents.
 1.2 Historical development of Pharmaceutics
 ANCIENT ERA – From the dawn of civilization up to 1600 AD
 EMPIRIC ERA – Spanning 1600 to 1940, marked by practical experience and
observation
 INDUSTRIALIZATION ERA – Between 1940 and 1970, characterized by mass
production and technological advances
 PATIENT CARE ERA – From 1970 to today, focusing on personalized healthcare and
clinical services
 BIOTECHNOLOGY AND GENETIC ENGINEERING ERA – The emerging
frontier shaping the future of medicine

Ancient Era

 Pharmacy and medicine were unified.

 Use of natural substances (plants, minerals, animal products).
 Earliest records in:
 Sumerian tablets (Mesopotamia)
 Ebers Papyrus (Egypt, ~1500 BC)
 Charaka & Sushruta Samhitas (India)
 Dioscorides' De Materia Medica (Greece)

 Early healers applied natural remedies like leaves, mud, and cool water to control
bleeding and promote wound recovery.
 These techniques were inspired by careful observation of how animals naturally mend
their injuries.
 Their healing knowledge was recorded on clay tablets, representing some of the earliest
written medical documentation.
 In ancient Babylonia, priests, pharmacists, and physicians maintained records of
pharmaceutical practices, marking the dawn of organized medicine and drug science.
 Hippocrates is celebrated as the Father of Medicine for his foundational contributions.
 Theophrastus, known as the Father of Botany, was among the first scientists to study
plants systematically.
 Mithridates earned the title Father of Toxicology through his research on the harmful
effects of various plants.

EMPIRIC ERA
 The Pharmacopeia evolved into an essential regulatory reference for pharmacists.

 In 1751, Benjamin Franklin established the first hospital, which included a pharmacy
staffed by Jonathan Roberts, recognized as the inaugural hospital pharmacist.
  The Philadelphia College of Pharmacy was founded in 1821, marking a significant
milestone in pharmaceutical education.

 William Proctor, hailed as the father of American Pharmacy, dedicated his career to
advancing the profession and operated his own apothecary shop.

 Pharmacists made their most notable scientific contributions in the field of chemistry.

Renaissance to Pre-Industrial Era (1500–1800 AD)

 Invention of printing press led to widespread pharmacopoeias.

 Emergence of compounding pharmacies.
 Recognition of the need for standardization of doses.
 Beginning of scientific classification of drugs.

Industrial Revolution
 Mass production of drugs began.
 Birth of pharmaceutical industry.
 Discovery of morphine, quinine, digitalis.
 Introduction of dosage forms like tablets, capsules, and ointments.

BIOTECHNOLOGY AND GENETIC ENGINEERING ERA

20th Century – Modern Pharmaceutics

Emergence of physical pharmacy as a scientific field.
Development of:
 Controlled release systems
 Parenteral products
 Sterile techniques
 Pharmacokinetics and biopharmaceutics gained importance.
 Introduction of regulatory standards (e.g., FDA, ICH).

21st Century – Advanced Drug Delivery

 Use of nanotechnology, biotechnology, and 3D printing in dosage form design.
 Focus on personalized medicine, targeted delivery, and smart drug systems.
 Integration of AI, computational pharmaceutics, and QbD (Quality by Design).
 1.3 Pharmaceutical industry overview
Global Landscape

 Grounded in extensive scientific research

 Facing tighter margins on revenue and earnings
 Encountering rising expenses and heightened risks in drug development
 Shifting swiftly from a primarily U.S. and E.U. focus to a truly global arena for both
drug innovation and commercialization

INDIAN OVERVIEW
 Demonstrates strong self-sufficiency by manufacturing 70% of essential bulk drugs
domestically
 Benefits from highly competitive production costs
 Maintains relatively low expenditures on research and development
 Innovates through the creation of affordable and efficient technologies
 Shows a growing positive trade balance within the pharmaceutical industry
 Serves as a reliable and economical hub for sourcing generic medications
 Particularly advantageous for drugs nearing patent expiration in the upcoming years

Industry Evolution
 Worldwide Sector Development
 Growth and Transformation in India's Industry
Global Pharmaceutical Industry Evolution
 In the 1940s and 1950s:
o The discovery of penicillin marked a groundbreaking milestone, firmly rooting
itself as a cornerstone in the nascent pharmaceutical sector during its research
and development phase.
 In the 1960s:
o The industry experienced rapid growth, fuelled by a wave of significant
innovations safeguarded by lasting patent rights.
o Regulatory oversight on clinical trials and marketing remained minimal,
coinciding with a surge in healthcare expenditures driven by thriving
economies.
o Medical professionals held the reins of prescribing decisions, largely indifferent
to drug pricing but influenced by pharmaceutical representatives, which led to
the proliferation of "me-too" drugs—medications offering similar therapeutic
effects.
  During the 1970s – Regulatory oversight of clinical trials became more
stringent, significantly driving up the costs associated with drug development.
– New laws introduced fixed patent durations, usually lasting 20 years from the
initial research filing, which paved the way for the rise of "generic" drugs and
triggered a notable surge in research and development expenditures.
 In the 1980s – Numerous nations implemented controls on drug pricing or
reimbursement, effectively banning price hikes. The pharmaceutical sector
found itself without sufficient public or political backing to oppose these
reforms. – This decade also saw the birth of numerous small biotechnology
startups, marking a shift in the industry landscape.
 Economic Challenges in the 1990s – A global recession tightened budgets,
limiting government and employer funding for healthcare services. – In 1993,
total pharmaceutical sales dropped by 11%, yet the top four generic drug
manufacturers saw their sales surge between 10% and 63%. – This scenario
intensified demands on the pharmaceutical sector to produce authentic, high-
quality products.
 Trends from 2000 Onward – Despite significant hikes in research and
development spending, the approval rate for new drugs has steadily declined.
– Consequently, many pharmaceutical companies are prioritizing strategies to
boost the efficiency and output of their R&D efforts.

Characteristics of industry:
 Revenue growth is primarily fueled by the introduction of innovative products.
 The presence of patent rights incentivizes ongoing development of new offerings.
 Marketing efforts are focused directly on healthcare professionals, particularly doctors.
 Government regulations and institutional purchasers limit the ability to raise prices.
 Establishing a robust distribution system is essential for mass-market pharmaceuticals
in most regions.
Classification Of Industry
Drug Categories:
- Proprietary (Branded) Medications
- Generic Drugs
- Orphan Drugs (for rare diseases)
 Active Pharmaceutical Ingredients (APIs)
 Contract Research and Manufacturing Services (CRAMS)
 Biopharmaceuticals (Bio Pharma)

Regulatory Frameworks Governing the

Pharmaceutical Sector
 International Standards (Global)
 Regulations Specific to India (Indian)
 Global Landscape
Despite ongoing debates, a wave of regulatory and legislative reforms has paved the
way for growth in this sector of the pharmaceutical industry.
 In 2004, the European Medicines Agency (EMEA) laid down a legal foundation for
biosimilars, followed by detailed approval guidelines introduced in 2007.
 Both the EMEA and the FDA granted Novartis approval for Omnitrope, a biosimilar
growth hormone developed to rival Pfizer's biologic, Genotropin.

Indian Regulatory Framework

 The Drugs and Cosmetics Act, 1940: This legislation oversees the
importation, production, distribution, and sale of pharmaceuticals across India.
 Schedule M: Outlined within the Drugs and Cosmetics Act, this schedule
details the essential standards for factory infrastructure, materials, machinery,
and the minimum spatial requirements necessary for manufacturing specific
drug categories.
 Schedule T: This section sets forth the Good Manufacturing Practices (GMP)
standards specifically for the production of Ayurvedic, Siddha, and Unani
medicines.
 Schedule Y: Governs the regulatory framework for clinical trials under the
Drugs and Cosmetics Act, ensuring compliance with legislative mandates. The
Pharmacy Act, 1948: This act regulates the pharmacy profession in India. It
mandates the establishment of the Central Pharmacy Council by the Central
Government and State Pharmacy Councils by respective State Governments to
oversee pharmacy practice and standards.
 The Drugs and Magic Remedies (Objectionable Advertisement) Act, 1954:
This legislation regulates advertisements related to drugs and bans promotions
claiming magical or miraculous healing properties.
 The Narcotic Drugs and Psychotropic Substances Act, 1985: This law
governs the control, regulation, and management of narcotic drugs and
psychotropic substances.
 The Medicinal and Toilet Preparations (Excise Duties) Act, 1956: This act
establishes the framework for imposing and collecting excise duties on
medicinal and toilet products.
 The Drugs Price Control Order (DPCO), 1995: Issued under the Essential
Commodities Act, 1955, this order empowers the Government of India to
regulate drug prices. It outlines the list of drugs under price control, the
procedures for setting prices, enforcement mechanisms, and penalties for
violations. The National Pharmaceutical Pricing Authority (NPPA) is entrusted
with implementing these provisions.
  Good Clinical Practice (GCP) Guidelines: The Ministry of Health, in
collaboration with the Drugs Controller General of India (DCGI) and the Indian
Council for Medical Research (ICMR), has introduced draft guidelines
governing research involving human participants. These GCP standards draw
heavily from the Declaration of Helsinki, World Health Organization (WHO)
protocols, and the International Conference on Harmonization (ICH) criteria for
ethical clinical practice.
 Key legislation impacting the pharmaceutical sector in India includes:
 The Industries (Development and Regulation) Act, 1951
 The Trade and Merchandise Marks Act, 1958
 The Indian Patent and Design Act, 1970
 The Factories Act

Regulatory Authorities:
 Ministry of Chemicals and Fertilisers (MoC&F):
 This ministry oversees the formulation of policies, strategic planning, development
initiatives, and regulatory frameworks concerning Chemicals, Petrochemicals, and
Pharmaceuticals.
 Department of Chemicals & Petro-Chemicals: Focused on fostering the expansion
and advancement of the pharmaceutical sector within India, this department also aims
to attract domestic and foreign investments.
 India introduced its inaugural comprehensive pharmaceutical policy in 1978, followed
by updated guidelines issued in 1986, 1994, and most recently in 2002.

1.4 REGULATORY FRAMEWORKS (FDA, Etc)

INTRODUCTION : U.S. Food and Drug Administration (FDA)
 A federal agency operating under the United States government.

 Part of the Department of Health and Human Services.

 Established on June 30, 1906, marking over a century of service.

 Founded by President Theodore Roosevelt and chemist Harvey Washington Wiley.

 Main offices located at White Oak Campus, 10903 New Hampshire Avenue, Silver
Spring, Maryland.

 Functions as an executive agency.

 Current Commissioner of Foods and Drugs: Scott Gottlieb.
  Overseen by the Department of Health and Human Services as its parent organization.

DEFINITION OF FDA : The regulatory frame works of the FDA (Food and Drug
administration ) are structured to ensure the safety ,efficacy and quality of food
,drugs,cosmetics,biologics, and medical devices in the united states.

HISTORY OF FDA :
 Prior to the 1900s, federal oversight of the production and sale of food and medicines
within the United States was minimal.
 In June 1906, President Theodore Roosevelt enacted the landmark "Pure Food and Drug
Act."

 This legislation introduced penalties for the interstate distribution of drugs that were
"adulterated," meaning their active pharmaceutical ingredients (APIs) lacked clearly
stated standards of strength, quality, or purity on labels or were not recognized in the
United States Pharmacopeia (USP) or National Formulary (NF).

 The Act also prohibited the "misbranding" of both food products and pharmaceuticals,
aiming to protect consumers from deceptive practices.

 In 1927, the regulatory responsibilities of the Bureau of Chemistry were transferred to

a newly established USDA division called the Food, Drug, and Insecticide
Organization.

 Just three years later, this entity was renamed the Food and Drug Administration (FDA).

 On June 24, 1938, President Franklin Delano Roosevelt enacted the Federal Food,
Drug, and Cosmetic Act (FD&C Act), marking a significant milestone in food and drug
regulation.

Mission:
 The FDA is dedicated to safeguarding public health by ensuring that medicines and
foods are safe, effective, and secure.

 Beyond protection, the FDA drives progress by accelerating innovations that make
treatments more effective, safer, and affordable for everyone.

 We empower the public with reliable, science-backed information to help them make
informed choices about medicines and nutrition for better health.

 Additionally, the FDA oversees tobacco products with a focus on protecting public
health and reducing tobacco use among youth.
 FDA STRUCTURE:
 Center for Drug Evaluation and Research

 Center for Biologics Evaluation and Research

 Center for Devices and Radiological Health

 Center for Food Safety and Applied Nutrition

 Center for Tobacco Products

 Center for Veterinary Medicine

 National Center for Toxicological Research

Scope of FDA Oversight:

 Food Products, encompassing:

• Nutritional Supplements

• Packaged Drinking Water

• Additives Used in Food

• Infant Nutrition Formulas

 Medications, covering:

• Prescription Drugs (including both brand-name and generics)

• Over-the-Counter (OTC) Medications

 Biological Products, such as:

• Vaccinations

• Blood and Related Components

• Therapies Based on Cells and Genes

• Human Tissue and Tissue-Derived Products

• Extracts Used for Allergy Treatments

 Medical Devices:
o Basic tools such as tongue depressors and bedpans

o Advanced equipment including cardiac pacemakers

o Devices used in dental care

o Surgical implants and artificial limbs

 Electronic Devices that Emit Radiation:
o Household appliances like microwave ovens

o Diagnostic tools such as X-ray machines

o Laser-based instruments

o Equipment for ultrasonic therapy

o Lighting devices including mercury vapor lamps

o Sunlamps used for therapeutic or cosmetic purposes

 Cosmetics and Personal Care:

o Colorants and pigments incorporated in makeup and grooming products
o Moisturizing creams and cleansing agents for skin care
o Nail varnishes and aromatic perfumes

 Veterinary Supplies and Nutrition:

o Animal feed designed for livestock
o Dietary products tailored for pets
o Veterinary pharmaceuticals and medical devices
 Tobacco Products:
o Factory-made cigarettes
o Loose tobacco intended for cigarette production
o Tobacco for rolling your own cigarettes
o Smokeless tobacco varieties

FDA's Regulatory Boundaries:

 Advertising The Federal Trade Commission (FTC) oversees a wide range of
advertising activities. Its mission is to shield consumers by preventing unfair,
misleading, or fraudulent marketing practices.

 Alcohol The Alcohol and Tobacco Tax and Trade Bureau (TTB), part of the Department
of the Treasury, governs various facets of alcohol including its production, import,
wholesale distribution, labeling, and advertising.

Consumer Safety and Drug Enforcement

 Consumer Product Safety Commission (CPSC) The CPSC is dedicated to protecting
the public by ensuring that everyday items—ranging from toys and cribs to power tools,
cigarette lighters, and household chemicals—are free from hazards such as fire,
electrical shocks, chemical dangers, or mechanical risks.
  Drug Enforcement Administration (DEA) Operating under the Department of
Justice, the DEA enforces U.S. laws regulating controlled substances. This includes
overseeing the lawful production, distribution, and dispensing of these drugs to prevent
abuse and illegal activity.

 Meat and Poultry

The Food Safety and Inspection Service, part of the U.S. Department of Agriculture,
oversees the safety standards and labeling requirements for conventional meats, poultry,
and select egg products.
 Pesticide
The Environmental Protection Agency (EPA) manages regulations concerning
pesticides, including establishing permissible levels for pesticide application during
crop cultivation and processing, as well as the maximum residues allowed on food items
at the point of purchase.

 Animal Disease Vaccines

The U.S. Department of Agriculture’s Animal and Plant Health Inspection Service
(APHIS), through its Center for Veterinary Biologics, oversees the regulation of
veterinary vaccines and other related biological products used in animal health.

 Drinking Water Standards

The Environmental Protection Agency (EPA) is responsible for setting and enforcing
national guidelines for drinking water quality. These standards apply to municipal water
systems, ensuring that tap water remains safe by limiting contaminant levels.

FDA Advisory Panels

 These panels offer the FDA unbiased guidance from external specialists on matters
concerning human and animal medications, vaccines, biological products, medical
devices, and food safety.
 Typically, each panel is composed of a chairperson, multiple members, and
representatives from consumer groups, industry sectors, and occasionally patients. For
specific meetings, additional experts with specialized knowledge may be invited to
contribute.
 While these panels provide valuable recommendations, the FDA retains the authority
to make the ultimate decisions.

CONCLUSION:
The Food and Drug Administration (FDA) is responsible for protecting the public health by
assuring the safety, efficacy, and security of human and veterinary drugs, biological products,
medical devices, our nation's food supply, cosmetics, and products that emit radiation.
 1.5 PHARMACEUTICAL PRODUCT DEVELOPMENT
PROCESS:
INTRODUCTION:
A pharmaceutical product begins its journey when a novel chemical compound, known as a
drug moiety, is identified. At this stage, it is classified as an experimental medication. With the
collaboration of specialized drug development teams, the compound undergoes rigorous
preclinical and clinical testing phases. These stages are regulated and must receive approval
through Investigational New Drug Applications (INDAs) and New Drug Applications (NDAs),
respectively. Once approved, the drug is launched into the market and distributed across various
regions for therapeutic use.

Product Development Process

[Link] Needs: This initial phase involves thoroughly researching and
understanding the market, customer pain points, and unmet demands. It requires
gathering insights through surveys, interviews, and data analysis to pinpoint
opportunities where a new product can add value.

[Link] Ideas: Once needs are identified, brainstorming sessions and creative
thinking techniques are employed to develop a wide range of potential solutions. This
stage encourages innovation and collaboration to explore diverse concepts before
narrowing down to the most promising ones.

[Link] and Building the Product: In this critical phase, the selected idea is
transformed into a tangible product. It includes detailed design work, prototyping,
testing, and iterative refinement to ensure the product meets quality standards and user
expectations. Cross-functional teams often collaborate closely to address technical and
aesthetic aspects.

[Link] and Promoting to Customers: After finalizing the product, the focus
shifts to market introduction. This involves strategic marketing campaigns, distribution
planning, and customer engagement efforts to create awareness and drive adoption.
Feedback from early users is also collected to inform future improvements.

Objectives:
 Develop a high-quality product along with its manufacturing processes to reliably
achieve the desired product performance.

 Ensure the therapeutic component within the formulation is appropriate, safe, effective,
and free from toxicity.
 Deliver a consistent and predictable therapeutic effect from the drug.
  Assess the feasibility of large-scale production while maintaining consistent product
quality.

 Identify potential risks early in the development process.

 Determine critical material characteristics and process variables that influence the
quality attributes of the drug product.

REGULATION RELATED TO PREFORMULATION : It is the first step in drug

development, focusing on studying the drug’s physical and chemical traits. This helps create
safe, effective, and stable dosage forms.

Main Goals:
 Identify the drug’s physical and chemical properties.

 Check its stability and reaction rates in different conditions.

 Test compatibility with common excipients.

 Help choose the best dosage form.

 Provide guidance on manufacturing and storage to keep quality. The process of

developing Ayurvedic medicines involves both preclinical and clinical steps, similar to
modern drug development but with unique considerations. Preclinical studies focus on
safety and efficacy in lab settings (in vitro) and in animal models (in vivo), while
 clinical trials involve human subjects. These phases aim to gather evidence of safety
and effectiveness before regulatory approval.

 1. Preclinical Studies:

 In vitro studies:
 These studies evaluate the drug's effect on cells and tissues in a controlled laboratory
environment. They assess the drug's mechanism of action, potential toxicity, and ability
to interact with biological targets related to the disease.

 In vivo studies:
 These studies involve testing the drug on animals to evaluate its efficacy, safety, and
pharmacokinetic properties (how the body processes the drug).

 Pharmacokinetics (PK):
 This involves studying how the drug is absorbed, distributed, metabolized, and excreted
by the body.

 Pharmacodynamics (PD):
 This involves studying the drug's effects on the body and its mechanism of action.

 Toxicology:
 This involves assessing the potential harmful effects of the drug on different organs and
systems.

 Formulation development:
 This involves optimizing the drug's physical and chemical properties for optimal
delivery and stability.

 Manufacturing:
 This involves developing a reliable and consistent manufacturing process for the drug.

 2. Clinical Trials:

 Phase I: Human Pharmacology:

 This phase involves a small group of healthy volunteers to assess the drug's safety and
dosage.

 Phase II: Therapeutic Exploratory Trials:

 This phase involves a larger group of patients with the targeted condition to further
assess the drug's safety and efficacy.

 Phase III: Therapeutic Confirmatory Trials:

 This phase involves a large, randomized, controlled trial to confirm the drug's
effectiveness and safety in a larger population.

 Phase IV: Post-marketing Surveillance:

 This phase involves ongoing monitoring of the drug's safety and effectiveness after it
has been approved and is being used by the public.

 Specific Considerations for Ayurvedic Medicines:

 Classical Texts:
 Ayurvedic drug development often involves thorough study of classical texts (like
the Charaka Samhita, Sushruta Samhita, etc.) for identifying potential drug candidates
and understanding their therapeutic properties.

 Traditional Knowledge:
 Ayurvedic principles
like Rasa (taste), Guna (property), Veerya (potency), Vipaka (post-digestive effect),
and Dosha Karma (effect on bodily humors) are taken into consideration during the
drug development process, according to the Central Council for Research in Ayurvedic
Sciences (CCRAS).

 Reverse Pharmacology:
 This approach involves observing the effects of Ayurvedic medicines in patients
(bedside) and then conducting scientific studies to understand the underlying
mechanisms of action (bench).

 Interdisciplinary Approach:
 Integrating Ayurvedic principles with modern scientific methods is crucial for
validating Ayurvedic drugs and therapies.

 Regulatory Guidelines:
 Ayurvedic drug development is governed by specific regulatory guidelines, such as
the New Drugs and Clinical Trials (NDCT) Rules, which outline the requirements for
preclinical and clinical studies.

 By combining traditional knowledge with modern scientific methods, the drug

discovery and development process for Ayurvedic medicines can lead to safe and
effective therapies for various ailments.
ICH Guidelines for Small Molecule Drugs:
 Q1D: Utilization of bracketing and matrixing strategies to optimize stability testing for
new drug substances (NDS) and finished products.

 Q1C: Protocols for conducting stability assessments on newly developed dosage forms.

 Q1A(R2): Comprehensive stability evaluation requirements for both new drug

substances and their corresponding products.

 Q1B: Guidelines for photostability testing of new drug substances and products to
ensure light-induced degradation is assessed.

 Q3A: Identification and control of impurities present in new drug substances and
finished products.

 Q3B(R): Management of impurities specifically within new drug products.

 Q7A: Good Manufacturing Practice (GMP) standards tailored for active

pharmaceutical ingredients (APIs).

 Q3C: Regulations concerning residual solvents, including detailed tables and lists
relevant to tablets and other dosage forms.

Stages of Development of a New Drug Phases

1. Preclinical Phase:
 This stage involves testing on animals to evaluate various characteristics and safety
parameters of a drug candidate before moving forward in development.

 During this phase, the innovator assesses the drug's toxicological and pharmacological
properties through both in vivo and in vitro animal studies.

 The USFDA mandates that, at this stage, a comprehensive pharmacological profile

must be established, toxicity levels identified, and short-term toxicity evaluations
performed.

[Link] Phase :

This phase is typically divided into four distinct stages:

[Link] 0 (Microdosing)

[Link] 1 (Human Pharmacology)

[Link] 2 (Therapeutic Exploratory Trials)

4. Phase 3 (Therapeutic Confirmatory Trials)

5. Phase 4 (Post-Marketing Surveillance)

[Link] 0
 This initial stage of a clinical trial focuses on exploration.

 It involves a very limited group of participants, typically fewer than 15 individuals.

 Researchers administer a minimal dose of the drug to confirm its safety in humans
before progressing to higher doses in subsequent phases.

[Link] 1(Human Pharmacology)

 Conducted with a small cohort of healthy volunteers, usually ranging from 20 to 100
participants.

 Phase 1 primarily aims to uncover how the drug behaves metabolically and
pharmacologically in humans, along with identifying any side effects that emerge as
doses increase.

 This initial phase is crucial for establishing the drug's safety profile.
 Comprehensive data on the drug’s pharmacokinetics and pharmacodynamics must be
gathered during Phase 1.

 About 70% of drugs that pass through this stage advance to subsequent phases of
development.

[Link] 2 (Therapeutic Exploratory Trials)

 The goal of Phase 2 clinical trials is to collect early proof of a drug’s effectiveness in
treating a targeted illness or condition.

 This phase also plays a crucial role in uncovering typical short-term adverse effects and
evaluating the safety profile of the drug.
 Conducted with meticulous planning and close oversight, these studies involve a
broader group of patients, usually between 20 and 300 individuals.
 The duration of Phase 2 can span from a few months to as long as two years, depending
on the study design.

 Roughly one out of every three drugs tested in this phase progresses to the next stage
of clinical development.

4. Phase 3 (Therapeutic Confirmatory Trials)

 This phase involves both expanded controlled studies and some uncontrolled trials.

 The main goal is to evaluate the treatment's effectiveness and closely monitor any
adverse effects.

 Typically, Phase 3 enrolls between 300 and 3,000 participants who are affected by the
targeted disease or condition.
  For a drug to gain approval from the US FDA, it generally requires at least two
successful Phase 3 trials.

 These studies usually span 1 to 4 years, with roughly 25-30% of drugs advancing
beyond this stage.

5. Phase 4 (Post-Marketing Surveillance)

 Commonly referred to as Post Marketing Surveillance (PMS).

 Initiated after a drug receives approval and is available on the market.

 The primary goal is to evaluate the drug's safety across a broad, global patient
population.

 This phase is crucial for identifying rare or long-term side effects that may not have
appeared in earlier trials.

 Involves thousands of participants who are affected by the condition the drug is
designed to treat.

Duration Needed to Develop New Medications:

 The journey to create a new drug is notably lengthy and meticulous.

 At each phase of development, regulatory bodies rigorously evaluate the drug candidate
before it can reach the market.

 The Pharmaceutical Research and Manufacturers of America (PhRMA) estimates that

bringing a new drug from concept to market typically spans 12 to 15 years.

 This timeline generally includes approximately 6.5 years dedicated to discovery,

preclinical studies, and toxicity assessments; 1.5 years for Phase 1 clinical trials; around
2 years for Phase 2; about 3.5 years for Phase 3; followed by roughly 1.5 years for
regulatory review and approval.

 After approval, the drug often enters Phase 4, where ongoing monitoring collects
additional data on its safety and effectiveness.

Regulatory Approval Process

A).Investigational New Drug (IND) Application:

 After successful animal testing (preclinical studies), the sponsoring company submits
an IND application to regulatory bodies to gain permission for human clinical trials.

 The IND submission must provide detailed data including results from prior
experiments, specifying the methods, locations, and personnel involved in upcoming
studies.

 It should also describe the chemical composition of the investigational drug and explain
its biological mechanism of action.
  Information on toxicological findings from animal testing and the drug's manufacturing
process must be included.

 The IND application requires evaluation and approval by an Institutional Review Board
(IRB).

 Key components of the IND application encompass:

a) Pharmacological and toxicology studies conducted on animals.

b) Detailed manufacturing data for the drug candidate.

c) Clinical trial protocols along with information about the investigators conducting
the studies.

B) New Drug Application (NDA)

 The NDA serves as the formal request submitted by drug developers seeking
authorization from regulatory bodies to market and sell a new pharmaceutical product
within a specific country.
 The primary purpose of the NDA is to supply comprehensive data enabling regulatory
reviewers to make critical evaluations regarding: a. The safety and effectiveness of the
drug. b. The suitability and accuracy of the drug’s labeling. c. The adequacy of
manufacturing processes and quality control measures to ensure the drug’s identity,
potency, quality, and purity are consistently maintained.

 This submission provides a complete and detailed overview of the new drug,
encompassing all necessary information for regulatory assessment.

 Once all clinical trial stages are successfully completed, the sponsor submits a New
Drug Application (NDA) to the regulatory body to demonstrate the drug's safety and
effectiveness.
 The NDA compiles comprehensive scientific data collected throughout the drug
development process.

 Given the extensive volume of information included in the NDA, regulatory agencies
require sufficient time to thoroughly evaluate every detail provided.
 M1U2 PHARAMACEUTICAL DOSAGE FORMS
2.1 CLASSIFICATION OF DOSAGE FORMS

Introduction
 Dosage Form (Medicines) = Active Pharmaceutical Ingredient (API) + Excipients The
physical form through which drug molecules are transported to their target sites within
the body.

 Drug (Active Pharmaceutical Ingredient) A chemical substance designed for

diagnosing, treating, or preventing diseases.

Alternatively, the API is the component of a medication responsible for its therapeutic
effects.

 Excipients

o These substances do not contribute to the drug's therapeutic impact.

o Often called inert or inactive ingredients, excipients generally lack

pharmacological activity.

o Common examples include binders, colorants, preservatives, flavor enhancers,

sweeteners, and dyes.

DEFINATION OF DOSAGE FORMS :

A pharmaceutical dosage form refers to the specific physical state in which a medication is
prepared and administered. This can include solids like tablets and capsules, liquids such as
syrups and injections, or gases like inhalers. The design of these forms ensures the drug
reaches targeted areas within the body effectively and safely.

Why Are Dosage Forms Essential?

[Link]
 Shields the medication from external factors, such as in coated tablets and sealed
ampoules.

 Prevents the drug from breaking down due to stomach acids.

[Link] Therapeutic Effectiveness

 Delivers the drug precisely to the target area, like ointments applied directly to the skin.
 Administers medication directly into body cavities, for example, rectal and vaginal
formulations.
  Ensures the drug acts efficiently within the bloodstream, as seen with injections.

 Controls the release rate of the drug, using modified-release systems.

 Boosts the absorption of drugs that have a limited window for uptake, such as gastro-
retentive dosage forms.

[Link] Patient Adherence

1. Ensuring precise dosing through standardized unit dose formats.

2. Minimizing dosing frequency by utilizing sustained-release and controlled-release

formulations.

3. Enhancing drug characteristics, such as using coated dosage forms to improve stability
and acceptability.

4. Simplifying the process of handling and administering medications for patients.

NEED OF DOSAGE FRMS :

 Ensure the precise and safe administration of medications in a user-friendly
manner. Examples include tablets, capsules, and syrups.
 Shield drug compounds from exposure to air and moisture, preserving their
stability. For instance, coated capsules and sealed ampules serve this
purpose.
 Protect active ingredients from being degraded by stomach acid following
oral intake, such as with enteric-coated tablets.
 Mask unpleasant tastes or odors of medications to improve patient
compliance, using forms like capsules, coated tablets, or flavored syrups.
 Enable the formulation of liquid medications when the drug is insoluble or
unstable in the chosen medium, as seen in suspensions.
 Provide liquid dosage options for drugs that readily dissolve in the selected
vehicle, such as solutions.
 eliver targeted drug effects at specific sites using topical forms like
ointments, creams, and ear or nasal solutions.
 Administer medications through body cavities by means of rectal and
vaginal suppositories for localized treatment.
 Extend the duration of drug activity with controlled-release formulations
such as tablets, capsules, and suspensions designed for gradual medication
release.
  Implant drugs directly into tissues to provide sustained therapeutic
benefits.
 Enhance drug delivery efficiency via inhalation methods, employing
inhalants to reach the respiratory system effectively.

CLASSIFICATION OF DOSAGE FORMS :

BASED ON ROUTE OF ADMINISTRATION:

 Oral

 Topical

 Parenteral

 Rectal

 Vaginal

 Inhalational

 Ophthalmic

 Otic
 Nasal
 Oral Tablets, Capsules, Syrups ,suspension,
Emulsions, etc Dry powder Inhaler
(DPI),Pressurized metered dose inhaler
(pMDI) -Nebulizer, vaporizer.
Sub-lingual And Buccal Orally Disintegrating tablet (ODT),
Lozenges, Mouthwash, Toothpaste,
Ointment , Oral spray
Rectal and vaginal Ointment ,Suppository ,Enema ,Nutrient
enema
Parenteral (injection and infusions) Intravenous, Intramuscular ,Intracardiac,
Intraosseous,Intraperitoneal,
Intracerebral, Intrathecal ,Intradermal
,Subcutaneous .
TOPICAL ROUTE
Dermal Ointment, Liniment ,Paste ,Cream ,
Lotion , Lio balm, Medicated shampoo,
Dermal patch
Mucosal Ear drops, Eye drops, Nasal drops,
Ointment , Hydrogel, Nanosphere
suspension , Mucoadhesive microdisc
(microsphere tablet )
Percutaneous Transdermal patch etc…

BASED ON Physical State:

 Liquids

 Semisolids
 Solids

 Gases

Categories of Liquid Dosage Forms

Liquid medications are broadly divided into two primary categories:

 Single-phase (Monophasic) liquids

 Dual-phase (Biphasic) liquids

[Link]-phase (Monophasic) liquids

A monophasic dosage form is a liquid formulation where two or more ingredients are uniformly
combined within a single phase. This type of preparation is exemplified by a true solution,
where all components are completely dissolved and evenly distributed.

 Solutions are uniform liquid mixtures designed for either internal or external
application, containing one or more active substances fully dissolved in an appropriate
medium.

 The substance present in the largest amount within the solution is called the “solvent,”
whereas the substance found in smaller quantities is referred to as the “solute.”

Syrups
 Syrups are liquid formulations primarily composed of 60% to 85% sugar dissolved in
water, which may include flavor enhancers and active medicinal ingredients. Examples
include Chlorpheniramine maleate syrup and Chloral hydrate syrup.
 These preparations are categorized into flavored syrups and those containing medicinal
compounds. Simple syrup is a saturated solution of sucrose in purified water.

 The concentration of sugar is 66% w/w The syrups are sweet viscous preparations. The
syrups containing medicinal substances are called "Medicated syrups" and those
containing aromatic or flavoured sub-stances are known as "Flavoured syrups".

 Syrups are very commonly used for the following reasons:

 1. Syrups retards oxidation because it is partly hydrolysed into reducing sugars, such
as, lavulose and dextrose.

2. It prevents decomposition of many vegetable substances. Syrups have high osmotic

pressure which prevents growth of bacteria, fungi and moulds which are the chief
causes of decomposition in solutions of vegetable matter.

3. They are palatable. Due to the sweetness of sugar it is a valuable vehicle for the
administration of nauseous substances.

The syrups may be divided into two groups:-

(a) Syrups prepared by simple solution or admixture e.g. syrups, syrup ginger,
syrup orange and syrup lemon.
SYRUP IP

Sucrose-667 g

Purified water, sufficient to produce -1000 g

Add sucrose to purified water and heat it to dissolve sucrose with occasional stirring. Cool it
and add more of purified water to make the required weight.

GINGER SYRUP IP

Strong ginger tincture

50 ml

Syrup, sufficient to produce

1000 ml Mix.

(6) Syrups made by a process of extraction e.g. Tolu syrup.

Tolu balsam

TOLU SYRUP LP

12.5 g

Sucrose

660.0 g

Purified water sufficient to produce 1000.0 g

Add boiling purified water to the Tolu balsam contained in a tared vessel. Cover the vessel
lightly and boil the contents gently for half an hour, stirring frequently. Add purified water to
adjust the specified weight. Cool, filter the solution and add sucrose. Heat on a water-bath to
dissolve the sucrose. Finally add sufficient purified water to produce the required volume.
Mixtures
 A mixture is a liquid formulation designed for oral use, where one or more active
ingredients
 are either dissolved or suspended within an appropriate base.
 It is intended for short-term use only.
 Commonly prescribed to address acute ailments such as cough, indigestion, diarrhea,
and constipation.

Elixirs
 Elixirs are transparent, fragrant, sweetened hydroalcoholic mixtures, which may or may
not include medicinal ingredients, designed for oral administration. For example,
dexamethasone elixir.
 The formulation often contains a significant amount of ethanol or sugar, along with
antimicrobial agents that help maintain the product's stability over time.

Linctuses
 Linctuses are thick, syrupy oral solutions commonly used to soothe cough
symptoms. For example, Codeine Linctus is a typical preparation.

 These formulations include active ingredients that provide a protective coating,

calming effect, and help loosen mucus on the throat lining.

 Usually administered in small doses (around 5 ml), linctuses should be taken

straight without dilution, allowing the liquid to be slowly sipped and swallowed
to maximize their soothing benefits.

Lotions
 Lotions are fluid formulations designed for application on the skin without the need for
rubbing.
 They primarily serve localized effects such as cooling, soothing, or providing a
protective barrier.
 These can be categorized into water-based lotions and those containing alcohol or other
non-aqueous solvents.
 Common types include cleansing lotions, moisturizing lotions, and antiseptic lotions.

Biphasic Liquids
EMULSIONS & SUSPENSIONS
EMULSIONS

* Emulsions are the biphasic liquid dosage forms containing two immiscible
liquids that are made miscible by the addition of a surfactant.

*o/w emulsions

*w/o emulsions
SUSPENSIONS

Suspensions

Suspensions are the biphasic liquid dosage forms of medicaments in which the
finely divided solid particles are dispersed in a liquid vehicle. D

*Oral

Parenteral

*Topical

*Opthalmic

Fluoronetickone Opitanic

Semisolid Dosage forms

*Ointments

*Creams

*Pastes

*Ointment

*Creams

*Jellies
*Suppositories

OINTMENTS

*Ointments are semisolid preparations meant for external application to the skin
or mucous membrane.

*They usually contain medicament or medicaments dissolved, suspended or

emulsified in an ointment base.

CREAMS

*Creams are viscous semi solid emulsions which are meant for external
application.

*Softer consistency and light in weight.

*Aqueous creams and Oily creams

PASTES

*Pastes are semisolid preparations intended for external application to the skin.

*Usually very stiff and thick.

*Protective, absorptive and antiseptic.

JELLIES

*Jellies are transparent or translucent non greasy, semi solid preparations meant
for external application to the skin.

*Medicated, Lubricating jellies.

SUPPOSITORIES

*Suppositories are semi solid shaped dosage forms of medicaments intended for
insertion into body cavities other than mouth.

*Dissolves at body temperature.

*Rectum, vagina, nose and ear.

 Fast relief

POULTICES

*Poultices are soft, viscous wet masses of solid substances applied to the skin
for their fomentation action in order to provide relief from pain or reduce
inflammation or to act as counter irritant.

*Applied to affected part after heating with occasional stirring

SOLID DOSAGE FORMS

*Tablets and Capsules

*Powders and Granules

*Tablets: A tablet is a solid unit dosage form containing medicament or

medicament's compressed to form round, oval or square shape.

* Uncoated or coated tablets

* Buccal and Sublingual tablets

*Effervescent tablets

"Chewable tablets

*Lozenges and Pastilles

*Pills

Tablets

 Tablets are solid oral dosage forms of compressed powders or granules intended for oral
administration.

 They are unit dosage form of medication containing specific amount of drug.

 They are prepared with the aid of pharmaceutical excipients.

 They vary in size, shape, weight, hardness, thickness, disintegration and dissolution.

 They are the most widely used and convenient dosage form.

Types:

Compressed Tablets

Dispersible tablets

Chewable tablets

Film coated tablets

Enteric coated tablets

Effervescent tablets

Immediate release tablets

Sustained release tablets

Molded tablets

Hypodermic tablets

Dispensing tablets

Special Tablets

Sub-lingual tablets

Buccal tablets

Vaginal tablets

Rectal tablets

Dispersible Tablets

Tablets that disintegrates within few seconds in liquid making homogenous mixture before
administration to patient.
⚫e.g: Zinc DT 10

Chewable Tablets

Tablets that are chewed within buccal cavity before swallowing. They are immediate release
oral dosage forms that have to be chewed and swallowed.

⚫e.g: Albendazole chewable tablets

COATED TABLETS

Sugar coated tablets

Film coated tablets

"Enteric coated tablets

Sugar-Coated Tablets

Film Coated Tablets

BUCCAL AND SUBLINGUAL TABLETS

Sublingual and buccal medications are administered by placing them in the mouth, either under
the tongue (sublingual) or between the gum and the cheek(buccal).

*The medications dissolve rapidly and are absorbed through the mucous membranes of the
mouth, where they enter into the blood stream.

CHEWABLE TABLETS

*They are tablets that chewed prior to swallowing.

*They are designed for administration of drugs to children e.g. vitamin products.

Antacid formulations.

LOZENGES

* Lozenges are solid preparations consisting of sugar and gum, the latter giving strength and
cohesiveness to the lozenge and facilitating slow release of the medicament.
*It is used to medicate the mouth and throat for the slow administration of indigestion or cough
remedies.

PASTILLES

*Pastilles are solid medicated preparations designed to dissolve slowly in the mouth.

*They are softer than lozenges and their bases are either glycerol and gelatin, or acacia and
sugar

PILLS

*Pills are solid oral dosage forms of spherical shape prepared from one or more medicaments
incorporated with inert excipients.

*Pills are now rarely used.

CAPSULES

1.*Capsules are self contained solid oral dosage forms in which the medicament or
medicaments along with suitable excipients is enclosed in a empty gelatin shell.

[Link] are solid dosage forms in which medicinal agents and pharmaceutical ingredients
are enclosed within a small shell of gelatin.

They are manufactured using Gelatin which is made up of proteins extracted from animal
collagen.

Types:

1. Hard gelatin Capsules

[Link] gelatin Capsules

Hard gelatin capsule

Theses are the capsules which are made up of gelatin, sugar and water. The capsule shell
contains low moisture content. They are hard and cylindrical in shape. They contain
powders, granules or pellets inside the capsule.

Soft gelatin capsule

These are the capsules which are made up of gelatin, water, glycerin or sorbitol. It contains
high moisture than hard gelatin capsule. It is used for the filing of liquid or semisolid
preparations. They are soft and vary in shape like round, oval, oblong, etc.

Sizes:

ooo(largest)-5(smallest)

Parts of Capsule:

[Link] body

2. Cap

POWDERS

* Pharmaceutical powders are intimate mixtures of dry finely divided drugs or chemicals
intended for internal or external use.

* The mixed powders may be stored in dry form and mixture prepared by the pharmacist
when required for dispensing, by suspending the powders in the appropriate vehicle.

GRANULES

* Granules are free flowing powder aggregates consisting of drugs and suitable excipients
and often supplied in single dose sachets.

* Some granules are placed on the tongue and swallowed with water, others are intended
to be dissolved in water before taking.

Effervescent granules evolve carbon di oxide when added to water.

GASES
 * Pharmaceutically gaseous dosage forms can be defined as any elastic aeroform fluids in
which the molecules are separated from one another and so have free paths.

[Link] Aerosols

[Link]

AEROSOLS

*A product that is packaged under pressure and contains therapeutically active ingredients
that are released upon activation of an appropriate valve system in the form of spray, mist,
foam etc.

*These are intended for topical application to the skin as well as local application into the
nose (nasal aerosols), mouth (lingual aerosols), or lungs (inhalation aerosols)

INHALERS

A special class of dosage forms consisting of a drug or combination of drugs, that by virtue
of their high vapor pressure can be carried by an air current into the nasal passage where
they exert their effect.

*Anti asthmatics & steroidal drugs

PARENTERALS

*Parenterals are defined as sterile dosage forms meant for" administration into body by
means of injection, infusion or implantation.

*Majorly through Intravenous, Intra muscular and Subcutaneously

PARENTERALS

 The term derived from Greek word 'Para' outside & 'Enterone' intestine.

 Parenterals are sterile solutions or suspension of drug in aqueous or oily vehicle

 Parenteral drugs are administered directly in to the veins, muscles or under the skin, or
more specialized tissues such as spinal cord.

 Term parenteral used for any drug/fluid whose delivery doesn't utilize the alimentary canal
for entering in to the body tissues.
 CLASSIFICATION

1. Small volume parenterals (SVP)

3. Large volume parenterals (LVP)

INJECTIONS
ADVANTAGES

 Useful for patients who cannot take drugs orally

 Rapid onset of action

 Useful for emergency situations

 Providing sustained drug delivery (implants, im depot inj)

 Avoid first pass metabolism

 Can inject drug directly in to a tissue (target drug delivery)

 Useful for delivering fluids, electrolytes, or nutrients (TPN)

 Can be done in hospitals, ambulatory infusion centers and home health care centers

 Complete bioavailability.

DISADVANTAGES

 Pain on injection

 Difficult to reverse an administered drug's effect.

 Sensitivity or allergic reaction at the site of injection.

 Requires strict control of sterility & non pyrogenicity than other formulation.

 Trained person is required.

 Require specialized equipment, devices, and techniques to prepare and administer drugs.

 More expensive and costly to produce.

PARENTERAL ROUTES

1. Intravenous

2. Intracisternal

3. Intramuscular

4. Peridural

5. Subcutaneous

6. Intraarticular

7. Intradermal

8 . Intracerebral

9 .Intra-arterial

[Link]

11. Intrathecal

1. Small volume parenterals (SVP)

SVP defn: An injection that is packed in containers labeled as containing 100 ml or less.
Small volume parenterals

Small volume intravenous injection is applied to an injection that is packaged in containers

labelled as containing 100 ml or less.

TYPES OF SVPs:

1. Solution:
2. Suspension:
3. Emulsion:
4. Dry powders:

[Link] volume parenterals

Defn: LVP are parenterals designed to provide :-

 Fluid

 Calories (dextrose solution)

 Electrolytes

 Combination of these

 Volume 101-1000 ml
LARGE VOLUME PARENTERALS REQUIREMENTS

 Sterile, non pyrogenic, free from particulate matter

 Volume 101-1000ml

 Single dose unit

 No preservative

 Clear solution except fat emulsion

 Isotonic, but hypertonic also administered in TPΝ

Types of Parenteral dosage Form

1. Injection

2. Infusion

3. Powder for injection

4. Concentrated solution for injection

[Link]

INTRODUCTION
Intravenous therapy (IV) is a therapy that delivers liquid substances directly into a vein (intra-
+ ven-+ -ous). The intravenous route of administration can be used for injections (with a
syringe at higher pressures) or infusions (typically using only the pressure supplied by gravity).
Intravenous infusions are commonly referred to as drips. The intravenous route is the fastest
way to deliver medications and fluid replacement throughout the body.

DEFINITION

Intravenous injection is the introduction of the small quantity of the drug into the vein by
venous puncture. Introduction of the medicine directly into the blood stream is called
intravenous injection.

PURPOSE

 To have fast action of the drug as in emergency.

 To give medications that are irritating or ineffective when given by other routes.

 To have the actions of medicines on the blood stream or the blood vessels.

 [Link]: Injections contain sterile solutions or suspension and are prepared by

dissolving the active ingredient and other substances in Water for Injection or other suitable
non-aqueous base or a mixture of both.

 Infusions These parenteral preparations are composed of a sterile aqueous solution with
water as a continuous phase. The preparations are free of bacterial endotoxins or pyrogens.
They contain no antimicrobial preservatives

 Powder for Injection: These are sterile solid preparations that are mixed or

 reconstituted with a diluent (usually 5% dextrose solution, normal saline. bacteriostatic

water, or sterile water for injection) before administration. These preparations are preferred
when drugs are not stable in solution.

Concentrated Solutions for Injections: These preparations

are diluted with water for injection before they are administered through injection or through
intravenous infusion

Implants: These solid sterile preparations are inserted in the tissue to release the active
ingredient for long periods. They are packed in sterile containers individually.
COMMON SITES OF IV INJECTION

Ventral aspect of elbow or forearm median cubical, basilica or cephalic veins.

Dorsal aspect of hand - brachial, cephalic or metacarpal veins. In the infants the scalp vein is
used.

I.V. injection

GENERAL INSTRUCTIONS

 Expel the air from the syringe before giving the injection by upholding it in upright
position and gently pressing the piston until a drop of solution comes to the tip of the
needle.

 Always dissolve the drug in correct amount of fluid to minimize the risk of adverse effect
of the medicine.

 Observe the patient closely for the signs of adverse reaction of the medicine and have
emergency drugs and the antidote in hand while injecting the medicine.

 Do not give the medicine if the injection site shows any edema or iv solution is not
following properly to avoid accidental administration of medicine into the surrounding
tissues.

 When giving iron preparation always confirms that the patient is not sensitive to it by
giving a test dose.
ADVANTAGES OF IV INJECTION

The therapeutic effect of the drug is seen as soon as it is administered to the patient.

IV medication also increases the chances of removal of toxins from the body cells, accelerating
the healing process

It also prevents the growth and spread of cancerous cells. Chemotherapy is given through IV
route so that the drug can move about the body and destroy the harmful cancerous cell.

DISADVANTAGES OF IV INJECTION

Very slim chances of drug recall, when the drug given to patient shows adverse effect

As the drug moves towards the target area quicker than the other methods the concentration of
the red blood cells present in the area can get dilated leading to anemia.
IV medications sometimes causes precipitate formation that causes embolism myocardial
damage.

COMPLICATIONS WITH INTRAVENOUS INJECTIONS

Infiltration

Hematoma

Air embolism

Phlebitis and thrombophlebitis

Extravascular injection

Intra-arterial injection

Allergic reaction

Sepsis

Speed shock

INFUSIONS
Definition of IV Fluids

The word "intravenous" as a noun refers to an intravenous fluid drip, a solution (usually a
balanced electrolyte solution) administered directly into the venous circulation.

Intravenous (iv) therapy is the insertion of a needle or catheter/cannula into a vein, based on
the physician's written prescription. The needle or catheter / cannula is attached to a sterile
tubing and a fluid container to provide medication and fluids.

Indications of IV Therapy

 provide fluid and electrolyte maintenance, restoration, and replacement

 Administer medication and nutritional replacement

 Administer blood and blood products

 Administer chemotherapy to cancer patients

 Administer key-controlled analgesics

 Keep a vein open for quick access

TYPES OF IV FLUIDS

1. Colloid:

Solutions that contain large molecules that don't pass the cell membranes.

When infused, they remain in the intravascular compartment and expand the intravascular
volume and they draw fluid from extravascular spaces via their higher oncotic pressure.

Volume expanders (Colloid)

-Are used to increase the blood volume following severe loss of blood (haemorrhage) or loss
of plasma (severe bums).

Expanders present in dextran, plasma, and albumin.

[Link]:

Solutions that contain small molecules that flow easily across the cell membranes, allowing for
transfer from the bloodstream into the cells and body tissues.

This will increase fluid volume in both the interstitial and intravascular spaces (Extravascular).

Itis subdivided into:

Isotonic.

Hypotonic.

Hypertonic

TYPES OF IV FLUIDS

Electrolyte solutions (Crystalloid)

-Fluids that consist of water and dissolved crystals, such as salts and sugar.

-Used as maintenance fluids to correct body fluids and electrolyte deficit.

Divided to different types.

Solutions Types

[Link]-tonic-solutions that have a lower osmolality than body fluids

[Link]-tonic-solutions that have ahigher osmolality than body fluids A

[Link]-solutions that have the same osmolality as body fluids

INTRAVENOUS INFUSION DEVICES

 Cannula

 IV Tubing set & Solution bag

 IV Pole and/or Pump

 Tape

How to calculate IV flowrates!

What is a drop factor?

Drop factor is the number of drops in one milliliter used in IV fluid administration (also called
drip factor). Anumber of different drop factors are available but the Commonest are:

1 10 drops/ml (blood set)

2 15drops/ml (regularset)

860 drops/ml (microdrop, burette)

How to calculate IV flow rates

The formula for working out flow rates is:22

volume (ml) X drop factor (gts/ml)

gtts/min

(flow rate)

time (min)

Example:

1500 ml IV Saline is ordered over 12 hours. Using a drop factor of 15 drops/ml, how many
drops per minute need to be delivered?

1500 (ml) X 15(drop/ml)

DIVIDED BY /12x 50 (gives us total minutes)
31drop/minute

COMPLICATIONS

Infection-redness, swelling and drainage at site; chills, fever, malaise,

headache

Tissue damage skin color change, sloughing of skin, discomfort at site

Phlebitis - heat, redness, tenderness, not hard and swollen

Thrombophlebitis -heat, redness, tendemess, hard and cordlike vein

Infiltration - Edema, pain, and coolness at the site

Catheter embolism -decrease BP, pain along vein, weak, rapid pulse, cyanosis of nail beds, loss
of consciousness

Circulatory overload -increased BP, distended jugular veins, rapid breathing, dyspnea, moist
cough and crackles

Electrolyte overload-signs depend on the specific electrolyte imbalance

Hematoma-ecchymosis, immediate swelling and leakage of blood at thesite, and hard painful
lumps at the site

Air embolism -tachycardia, dyspnea, hypotension, cyanosis, decreased level of consciousness

 [Link] PHARMACEUTICAL FORMULATION

1 .PRINCIPLES OF PHARMACEUTICAL FORMULATION

Principles for pharmaceutical formulation include preformulation studies to

assess drug properties, selecting suitable excipients that are compatible
with the drug, creating a stable dosage form (solid, liquid, etc.) for proper
drug delivery, and conducting stability testing to ensure product quality over
time. Key formulation factors are also dictated by the required route of
administration, such as enteral, parenteral, or topical, with each demanding
specific formulation approaches.

Key Principles:
Preformulation Studies:

Before formulation, understanding the physical and chemical properties of the

active pharmaceutical ingredient (API) is crucial. This includes its stability,
solubility, and interactions with potential excipients.

Excipient Selection:

Excipients are inactive ingredients that play vital roles in formulation. They are
chosen to enhance stability, control drug release, improve bioavailability, and
facilitate manufacturing.

Dosage Form Design:

The choice of dosage form (e.g., tablet, capsule, solution, cream) is based on the
drug's properties, patient needs, and desired route of administration.
Drug Stability:

Formulations must be stable under various environmental conditions to prevent

degradation of the API. This includes protection from moisture, light, and oxygen.

Bioavailability & Efficacy:

The formulation must ensure the drug is delivered to the target site in sufficient
quantity and at the right time to achieve the desired therapeutic effect.

Patient Compliance:

The formulation should be acceptable to the patient, considering factors like taste,
ease of administration, and overall usability.

Manufacturing & Scale-Up:

The formulation must be suitable for large-scale production, considering

processability, cost-effectiveness, and consistency.

Quality Control:

Throughout the development process, rigorous quality control measures are

implemented to ensure the final product meets specifications for safety, efficacy,
and purity.

Types of Formulations:

Solid Dosage Forms:

Tablets and capsules are common, offering advantages in terms of stability, dose
precision, and ease of handling.

Liquid Dosage Forms:

Solutions, suspensions, and emulsions provide an alternative for drugs that are
difficult to make into solid forms or require different administration methods.

Parenteral Formulations:
 Injections, which bypass the gastrointestinal tract, require sterile and stable
formulations with specific considerations for administration route and patient
suitability.

EXCIPIENTS AND THEIR FUNCTIONS

Definition:

An excipient is a pharmacologically inactive substance formulated alongside the active

pharmaceutical ingredient of a medication.

Purposes served by excipients:

 Provide bulk to the formulation.

 Facilitate drug absorption or solubility and other pharmacokinetic considerations.

 Aid in handling of "API" during manufacturing.

 Provide stability and prevent from [Link].


EXCIPIENTS IDEAL CHARACTERISTICS

Excipients are inactive substances formulated alongside the active pharmaceutical

ingredient (API) of a medication, and their ideal properties are crucial for drug development
and efficacy.
key ideal properties of excipients:

 Feasible: Excipients should be practical and manageable to incorporate into drug

formulations and manufacturing processes.

 No interaction with drug: They should not chemically or physically interact with the
active drug, ensuring the drug's stability and effectiveness.

 Pharmacologically inert: Excipients should not have any pharmacological activity

themselves, preventing unintended effects on the patient.
 Cost effective: The use of excipients should be economically viable for drug production.

 Stable for handling: Excipients need to be stable during storage, transportation, and
handling, maintaining their properties over time.

Functions of Excipients:
Binding:

Binders, like povidone, help hold powders together to form granules and improve
the mechanical strength of tablets.

Diluents/Fillers:

These increase the bulk of the tablet, ensuring it has the appropriate size and
weight for manufacturing and administration. Examples include lactose and
microcrystalline cellulose.

Disintegrants:

These help tablets break apart in the body, facilitating drug release and
absorption.

Lubricants:

Lubricants, such as magnesium stearate, reduce friction during tablet compression

and prevent sticking to punches.

Preservatives:

These prevent microbial growth, ensuring the drug's stability and safety during
storage.

Flavoring Agents, Sweeteners, Coloring Agents:

These improve the taste, appearance, and overall patient acceptability of the
medication.

Solubility Enhancers:

Some excipients help improve the solubility of poorly soluble drugs, aiding in their
absorption.

Coatings:
Coatings can protect the drug from moisture, light, or stomach acid, or control the
drug release.

Importance of Excipient Selection:

Choosing the right excipients is critical for several reasons:

Drug Stability:

Excipients can impact the stability of the active drug, affecting its shelf life and
efficacy.

Drug Delivery:

Excipients can influence how the drug is released and absorbed in the body.

Manufacturing Process:

Certain excipients are essential for the smooth and efficient production of tablets
and capsules.

Patient Experience:Excipients can affect the taste, appearance, and ease of

swallowing, which are important for patient compliance.

A list of Pharmaceutical Excipients used in pharmaceutical

preparations usually:

Fillers.

Buffering Agents.

Binders.

Chelating Agents.

Disintegrants.

Viscosity Imparting Agents.

Coatings.

Surface Active Agents.

Sorbents.
Humectants.

Antiadherent.

Lubricants.

Glidants.

Preservatives.

Antioxidants.

Flavoring Agents.

Sweeting Agents.

Coloring Agents.

Solvent & Co-solvent.

Fillers:

Fillers typically also fill out the size of a tablet or capsule, making it practical to produce and
convenient for the consumer to use.

Function of fillers:

Fillers add volume and/or mass to a drug substance, thereby facilitating precise metering and
handling thereof in the preparation of dosage forms. Used in tablets and capsules.

Typical features of fillers:

A good filler should typically be inert, compatible with the other components of the
formulation, non-hygroscopic, relatively cheap, compactible, and preferably tasteless or
pleasant tasting.

Examples:

Plant cellulose and dibasic calcium phosphate, are used popularly as fillers. A range of
vegetable fats and oils can be used in soft gelatin capsules. Other examples of fillers Include:
lactose, sucrose, glucose, mannitol, sorbitol, calcium carbonate, and magnesium stearate,
Binders:

Binders hold the ingredients in a tablet together, Binders ensure that tablets and granules can
be formed with required mechanical strength, and give volume to low active dose tablets.

Typical features of binders:

A binder should be compatible with other products of formulation and add sufficient
cohesion to the powders.

Classification and examples:

Binders are classified according to their application,

Solution binders are dissolved in a solvent (for example water or alcohol can be used in wet
granulation processes). Examples include gelatin, cellulose, cellulose derivatives,
polyvinylpyrrolidone, starch, sucrose and polyethylene glycol,

Dry binders are added to the powder blend, either after a wet granulation step, or as part of
a direct powder compression (DC) formula. Examples include cellulose, methyl cellulose,
polyvinylpyrrolidone and polyethylene glycol

Disintigrants:

Disintegrants are substances or mixture of substances added to the drug formulations, which
facilitate dispersion or breakup of tablets and contents of capsules into smaller particles for
quick dissolution when it comes in contact with water in the GIT.

Ideal properties of disintigrants:

Good hydration capacity, poor solubility, poor gel formation capacity.

Examples:

polyvinylpyrrolidone, carboxymethyl cellulose, sodium starch glycolate etc.

Coating Agent:

Coating is a process by which an essentially dry, outer layer of coating material is applied to
the surface of a dosage form and agents which are used in this coating process is called
coating agents.
Types:

Three types of coating agents are used pharmaceutically,

Film coating.

Sugar coating.

Compression coating.

Function of coating agents:

Protection, masking, elegance, ease of swallowing, identification etc...

Examples:

HPMC, MC, HPC etc..

CONCLUSION

The real importance of ensuring an excipient's quality and performance is are often
underestimated. In reality, the functionality of the excipient can help determine whether or
not a drug succeeds or fails. The possible consequences of not carefully choosing the best
excipient for formulation include manufacturing complications, compromised stability, poor
bioavailability of the API, unintended side-effects, and even serious adverse reaction or
death of the patient. So to avoid these undesirable outcomes it is very important to select the
right excipient for the formulation and guarantee its quality.

UNIT- 4 PHARMACEUTICAL MANUFACTURING AND

QUALITY CONTROL

GOOD MANUFACTURING PRACTICES (GMP AND cGMP)

What is GMP?
 GMP is that part of Quality assurance which ensures that the products are consistently
manufactured and controlled to the Quality standards appropriate to their intended use

"GMP" - A set of principles and procedures which, when followed by manufacturers for
therapeutic goods, goods, helps ensure that the products manufactured will have the required
quality.

What is cGMP?

⚫ Usually see "cGMP" - where c = current, to emphasize that the expectations are dynamic

Good Manufacturing Practices

⚫ A basic tenet of GMP is that quality cannot be tested into a batch of product but must be
built into each batch of product during all stages of the manufacturing process.

It is designed to minimize the risks involved in any pharmaceutical production that cannot
be eliminated through testing the final product.

Some of the main risks are

 Unexpected contamination of products, causing damage to health or even death.

 Incorrect labels on containers, which could mean that patients receive the wrong medicine.

 Insufficient or too much active ingredient, resulting in ineffective treatment or adverse

effects,

GMP helps boost pharmaceutical export opportunities

 Most countries will only accept import and sale of medicines that have been manufactured
to internationally recognized GMP.

 Governments seeking to promote their countries export of pharmaceuticals can do so by

making GMP mandatory for all pharmaceutical production and by training their inspectors
in GMP requirements.

GMP Covers...

 ALL aspects of production; from the starting materials, premises and equipment to the
training and personal hygiene of staff.
 Detailed, written procedures are essential for each process that could affect the quality of
the finished product.

 There must be systems to provide documented proof that correct procedures are
consistently followed at each step in the manufacturing process every time a product is
made,

GMP guidelines

 GMP as per Schedule "M"

 [Link]

 GMP as per WHO

[Link]

 GMP as per MCA now known as MHIRA

[Link]

 GMP as per TGA

[Link]

 GMP as per US FDA

[Link]

 GMP as per ICH guidelines

[Link]

GMP

 GMP in solid dosage forms

 GMP in semisolid dosage forms

 GMP in Liquid orals

 GMP in Parenterals Production

 GMP in Ayurvedic medicines

 GMP in Bio technological products

 GMP in Nutraceuticals and cosmeceuticals

 GMP in Homeopathic medicines

Ten Principles of GMP

1. Design and construct the facilities and equipments properly

2. Follow written procedures and Instructions

3. Document work

4. Validate work

5. Monitor facilities and equipment

6. Write step by step operating procedures and work on instructions

7. Design, develop and demonstrate job competence

8. Protect against contamination

[Link] components and product related processes

[Link] planned and periodic audits

Moving Beyond GMP Standards

 Aim to eliminate pollution entirely, striving for zero waste discharge.

 Embrace environmentally sustainable practices and technologies.

 Prioritize actions that ensure a healthier and more sustainable future.

 Uphold ethical principles in all aspects of life and work.

 Always plan with the ultimate goal in mind; starting without a clear vision risks failure.

Financial Advantages of Effective GMP

 Implementing Good Manufacturing Practices (GMP) and Quality Assurance (QA) delivers
clear cost savings and financial benefits.

 Well-designed facility layouts, streamlined workflows, robust documentation systems,

tightly controlled processes, and organized storage with accurate record-keeping
exemplify best manufacturing practices.

 These practices helphinimize work-in-progress and reduce inventory carrying expenses.

 They also prevent costs associated with quality failures, such as waste, rework, product
recalls, customer compensation, and damage to the company's reputation.

Essential Documentation in GMP

 Policies: Foundational guidelines that govern operations.

 Standard Operating Procedures (SOPs): Detailed instructions to ensure consistent

processes.

 Specifications: Defined criteria for materials and products.

 Master Formula Record (MFR): Comprehensive recipe for product manufacturing.

 Batch Manufacturing Record (BMR): Documentation of each production batch.

 Manuals: Reference materials for equipment and procedures.

 Master Plans and Files: Strategic documents outlining overall processes.

 Validation Protocols: Plans to confirm processes meet required standards.

 Forms and Formats: Standardized templates for data collection.

 Records: Archived evidence of all activities and compliance.

Prominent Regulatory Authorities

 International Council for Harmonisation (ICH): Access detailed standards and guidelines
at [Link].

 World Health Organization (WHO): Explore international health regulations and

initiatives via [Link].

 US. Food and Drug Administration (US FDA): Obtain comprehensive regulatory updates
at [Link].

 European Medicines Agency (EMA) and European Union (EU): Review European
regulatory policies at [Link].

Comparing GMP Standards Across Countries

 Globally, Good Manufacturing Practices (GMPs) share many common elements. Most
countries enforce requirements such as:
 Proper design, upkeep, and sanitation of equipment and facilities

 Development and formal approval of Standard Operating Procedures (SOPs)

 Establishment of an independent Quality unit, including Quality Control and/or Quality

Assurance teams

 Employment of well-trained staff and effective management

CGMP Guidelines for Finished Pharmaceuticals

1. General Guidelines

2. Organizational Structure & Staff

3. Facilities & Infrastructure

4. Equipment Standards

5. Management of Raw Materials & Packaging Components

6. Production Procedures & Process Oversight

7. Packaging and Labeling Management

8. Distribution and Handling Practices

 9. Quality Control Laboratory

10. Documentation and Reporting

11. Management of Returned and Recovered Products

1. General Provisions
1 Scope
2 Definitions

2. Structure & Team

1. Duties of the Quality Control Department
2. Required Qualifications for Staff
3. Roles and Responsibilities of Personnel
4. Engagement of External Advisors

[Link] and Facility Essentials

1. Architectural design and construction elements.
2. Illumination systems/Lighting .
3. Air quality management: ventilation, filtration, heating, and cooling.
4. Water supply and plumbing infrastructure.
5. Waste disposal and sewage management.
6. Hygiene facilities including washing and restrooms.
7. Overall sanitation standards.
8. Routine upkeep and maintenance procedures.

[Link] Overview

[Link], dimensions, and placement of equipment.

[Link] and build quality of machinery.

3. Procedures for cleaning and routine upkeep.

4. Types of equipment: automatic, mechanical, and electronic.

5. Use and maintenance of filtration systems.

Production and Process Oversight

1. Documented protocols and management of any deviations.
2. Proper introduction and handling of raw materials.
3. Accurate computation of production yield.
4. Clear labeling and identification of all equipment.
5. Systematic sampling and analysis of materials and products during production.
6. Adherence to strict timeframes throughout the manufacturing process.
7. Measures to prevent and control microbial contamination.
8. Procedures for reprocessing when necessary.

Packaging and Labeling Oversight

 Evaluation and selection criteria for materials used

 Procedures for issuing labels

 Execution of packaging and labeling tasks

 Requirements for tamper-evident packaging specifically for over-the-counter

(OTC) human medications

 Inspection protocols for finished drug products

 Guidelines for expiration date assignment

Handling and Distribution

1. Procedures for Efficient Warehousing
2. Protocols for Effective Distribution

Laboratory Control Overview

1. Fundamental Criteria
2. Procedures for Testing and Approval Prior to Distribution
3. Evaluation of Product Stability
4. Specific Testing Protocols
5. Management of Retained Samples
6. Use and Care of Laboratory Animals
7. Prevention and Monitoring of Penicillin Contamination

Documentation and Record-Keeping Essentials

1. General Guidelines: Fundamental principles governing all records.
2. Logs for Equipment Maintenance and Usage: Detailed tracking of cleaning and
operational history.
3. Records for Components, Containers, Closures, and Labeling: Documentation
covering all materials and packaging elements.
4. Master Production and Control Documentation: Comprehensive templates and
instructions for manufacturing processes.
5. Batch Production and Control Logs: Specific records for each production batch.
6. Review of Production Records: Systematic evaluation of production
documentation.
7. Laboratory Documentation: Records generated from lab testing and analysis.
8. Distribution Documentation: Tracking and records related to product distribution.
9. Customer Complaint Files: Documentation of feedback and issues reported by
customers.

Returned and Recovered Pharmaceutical Products

1. Overview of returned pharmaceutical items.

2 .Procedures for reclaiming drug products

PRACTICAL POINT - IDENTIFY AND CATEGORISE CLASSICAL AYURVEDIC

DOSAGE FORMS

Introduction to Ayurveda

Ayurveda represents a deeply rooted and extensively chronicled healthcare tradition originating
from the Indian subcontinent.

Ayurvedic remedies are formulated for both internal and external application, aimed at
diagnosing, treating, alleviating, or preventing illnesses and disorders in humans and animals.

These medicinal products are derived from natural origins, including plants, animals, and
minerals, emphasizing a holistic approach to health.

Categories of Ayurvedic Dosage Forms

 Ayurvedic medicines are prepared in various forms, broadly divided into four main
categories:

 Solid Forms: These include tablets and other compact preparations such as Pills, Gutika,
and Vatika.
 Semi-Solid Forms: This group consists of preparations like Avleha (herbal jams), Paka
(cooked formulations), Lepa (herbal pastes), and Ghrta (medicated ghee).

 Liquid Forms: These are fluid preparations such as Asava and Arista (fermented herbal
wines), Arka (distillates), Taila (medicated oils), and Dravaka (liquid extracts).

 Powdered Forms: This category covers fine powders and mineral-based formulations
including Bhasma, Satva, Mandura, Pisti, Parpati, Lavana, Kshara, and Churna.

Solid Dosage Forms

 Known as Vati or Gutika, these are medicinal preparations crafted into tablet or pill shapes.

 Examples include formulations like Muktadi Mahanjana and Chandroday Vartti, which are
commonly used in traditional medicine.

Semi-solid Dosage Forms

 Lepa: These are paste-like formulations designed for topical use on the skin. Examples
include Sinduradi Lepa and Pathyadi Lepa.
 Avleha or Leha and Paka: These semi-solid medicinal preparations are created by boiling
a mixture of sugar, jaggery, or sugar candy with specific herbal juices or decoctions to
achieve the desired consistency and therapeutic effect.

Liquid Dosage Forms

 Asava and Arista: These are therapeutic liquids created by immersing powdered herbs or
their decoctions in a sugary solution, often using sugar or jaggery. This mixture is left to
mature for a designated time, during which natural fermentation may occur, producing
alcohol and imparting calming effects.
 Arka: This is a distilled liquid preparation made by extracting the essence of certain crude
drugs or liquids soaked in water. The process uses a specialized distillation apparatus
known as the Arkayantra to obtain the final product.

 Dravaka: These are liquid formulations derived from substances like lavanas or ksharas.
They are typically produced through a distillation method, which may or may not involve
adding other liquids during the process.
Example: Sankha Dravaka
 Taila (Oils): Tailas are prepared by simmering fixed oils with a specific herbal decoction
and a finely ground paste of medicinal ingredients, following the exact recipe outlined in
traditional formulations.
Examples: Bhrangaraja Taila, Maha Narayan Taila

Powder Dosage Forms

 Sattva: These are water-soluble solid extracts derived from medicinal plants or
substances. For example, Gulvel Sattva is a common type.

 Pisti: Created by grinding the drug with specific liquids followed by exposure to sunlight
or moonlight, these preparations include examples like Praval Pisti and Mukta Pisti.

 Bhasma: This refers to the fine powder obtained through the calcination process, where
metals, minerals, or animal products are heated in sealed crucibles buried in pits and
covered with cow dung cakes (known as Puta). Examples include Godanti Bhasma and
Lauha Bhasma.

 Sattva: These are water-soluble solid extracts derived from medicinal plants or
substances. For example, Gulvel Sattva is a common type.

 Pisti: Created by grinding the drug with specific liquids followed by exposure to sunlight
or moonlight, these preparations include examples like Praval Pisti and Mukta Pisti.

 Bhasma: This refers to the fine powder obtained through the calcination process, where
metals, minerals, or animal products are heated in sealed crucibles buried in pits and
covered with cow dung cakes (known as Puta). Examples include Godanti Bhasma and
Lauha Bhasma.

4.2 Quality control and Quality Assurance

ययययययय यययय यययययययययययययय ययययय यययययय
ययययय यययय यययययययययय यययययययय ययययययययय ययययय य
( ययययययययय यययययययययययय य.ययय)
 Charaka warns that improperly prepared drugs can be fatal.
 Traditional Ayurvedic parameters: Prakriti, Guna, Prabhava, Rasa, Virya, etc
 “Sampat” denotes drug quality
 Siddhi Lakshana = Indicators of a properly prepared medicine (in-process QC).
 Healthcare success depends on safe, authentic, and effective drugs.
 Quality = Potency, purity, stability, efficacy – ensured from raw material to final product.
 Evaluation methods(Analytical parameters) for Quality control for formulations

What’s Ideal medicine ?

⚫⚫⚫⚫⚫⚫⚫⚫ ⚫⚫⚫⚫⚫⚫⚫ ⚫⚫⚫⚫⚫⚫⚫ ⚫⚫⚫⚫⚫⚫⚫⚫⚫⚫⚫ |
⚫⚫⚫⚫⚫⚫⚫⚫⚫⚫⚫⚫⚫⚫⚫⚫ ⚫⚫⚫⚫⚫⚫⚫⚫⚫ ⚫⚫⚫⚫⚫⚫⚫⚫⚫⚫⚫ ⚫
(Aṣṭāṅga Hṛdaya, Sūtrasthāna 1/13)

Definition of Quality
Juran's Definition:Quality is "Fitness for purpose," emphasizing a product or service's ability
to fulfill its intended function.

ISO Standard Definition:Quality is the "Degree to which a set of inherent characteristics fulfills
requirements," focusing on meeting predefined specifications and customer needs.

Functions of a Q.C LAB

 To ensure the quality of raw materials used in medicines.
 To ensure that the product is being manufactured as per G.M.P standards.
 To check the finished product for the required parameters.

Are QA and QC same terms?

 No,These both the terms are effectively different.

Most of the time we use both terms randomly, hence to study and understand the difference
between them is important.

Quality Assurance QualityQuality Control Control

 Quality Assurance is process oriented an Quality control is product oriented and focu
d focuses on defect prevention. ses on defect identification in the final Prod
uct
Proactive process- During Process Reactive process- Final Product
It identifies weakness in processes to Quality Control (Q.C) is crucial for
improve them ensuring Good Manufacturing Practices (G
.M.P)
Goal- Goal-
improve development and test processes identify defects after a product is developed
so that defects do not arise when the pro and before it’s released.
duct is being developed.

Staff Function Line Function

Quality is Implemented at the designing Quality is Implemented at the final stage

stage
Achieved by- Prevention of quality Achieved by-The activities or techniques
problems through planned and systematic used to achieve and maintain the product
activities including documentation. quality, process and service.

Responsibility-Everyone on the team Responsibility-Quality Control is usually the

involved in developing the product is responsibility of a specific team that tests the
responsible for Quality Assurance. product for defects.

NEED OF QUALITY CONTROL FOR AYURVEDIC FORMULATIONS

 Ensuring Safety
 Guaranteeing Efficacy
 Maintaining Consistency
 Building Public Trust
 Meeting Regulatory Requirements
 Facilitating Global Acceptance

Evaluation methods for Quality control With an example

The analytical parameters that can be supportive to standardize sneha kalpana .
1. Organoleptic (sensory)
 2. Physico-chemical
3. Microbial/pesticide/heavymetaltesting

[Link] Analysis
1 Color

2 Taste

3 Odour

4 Consistency

5 Appearance

Color: Assessing the color of the Sneha to ensure it matches the expected color based on the
ingredients and process.
Taste: While taste is not always a primary parameter, it can be useful in assessing the overall
quality and purity.
Odor: Evaluating the smell to ensure it is not rancid or abnormal.
Consistency: It assessed by observing the texture ,viscosity, and how the sneha behaves when
handled .
Appearance/Clarity : Observing the clarity and texture of the Sneha for any signs of
impurities or improper processing

2. Physico-Chemical Analysis
Sl. No. Test

1 Acid value(mg KOH/g oil)

2 Saponification value

3 Iodine value(mEq/g)

4 Free fatty acids

 5 High performance thin layer chromatography

6 Refractive index

7 TLC

8 Peroxide value

9 Presence of Rancidity(Kries)

10 PH

11 Viscosity

[Link] value
 Indicates the amount of free fatty acids (Triglycerides) present, which can be a sign of
degradation or rancidity.
 The acid number is expressed as the number of mgs of potassium hydroxide required to
neutralize one gram of fat.
 Acid value is the mass of potassium hydroxide (KOH) in milligrams that is required to
neutralize the free acid in one gram of the substance.

Significance :

Pharmaceutical Therapeutic

Rancidity: Higher acid values indicate a Bioavailability: The acid value of a

greater presence of free fatty acids, which substance can influence its absorption and
can lead to a rancid taste and odor in the fat bioavailability, particularly if it's a drug
or oil. administered orally or topically.

Quality: reflects the degree of degradation or Drug Interactions: In some cases, free fatty
spoilage. acids can interact with other drugs,
 A low acid value -higher quality, more stable potentially affecting their efficacy or causing
product. adverse reactions.
For example, a good quality oil may have an
acid value less than 0.1.

3. Saponification value
 The saponification value represents the number of milligrams of KOH or NaOH required
saponifying one gram of fat under the conditions specified. It is a measure of the average
molecular weight (or chain length) of all the fatty acids present.
 Saponification Value in Sneha Kalpana:
 In Sneha Kalpana, the saponification value is used to assess the purity, quality and
consistency of the medicated oils and ghee.

Significance :

Pharmaceutical Therapeutic

Stability: A higher saponification value Higher saponification values indicate a

(indicating more short-chain fatty acids) can higher proportion of shorter-chain fatty
sometimes be associated with greater acids.
susceptibility to oxidation and rancidity.

Quality Control: By measuring the The type and proportion of fatty acids affect
saponification value, manufacturers can how the Sneha is absorbed and metabolized
ensure batch-to-batch consistency and by the body, influencing its therapeutic
adherence to quality standards, which effects.
suggests that the oil or ghee is of Good
quality.

More number of free fatty acids in ghrita or

taila preparations indicates that ghrita or taila
preparations are damaged .

3. Iodine value(mEq/g)
  The iodine value is the amount of iodine in grams that is absorbed by 100 grams of a
chemical substance, most notably in fats and oils.
 The One application of the iodine value is the determination of the amount of unsaturation
in a fat
 Higher the iodine value, less stable the oil and more vulnerable it is to oxidation and free
radical production.

Significance:

Pharmaceutical Therapeutic

Stability: Iodine value directly correlates Increased Unsaturated Fats : Higher iodine
with the stability of Sneha. Oils with higher values are associated with increased levels of
iodine values are more prone to oxidation unsaturated fatty acids, which are generally
and rancidity, considered healthier than saturated fats.
Unsaturated fats can help lower LDL ("bad")
cholesterol and reduce the risk of heart
disease.

Unsaturation: The higher the iodine number, Improved Digestion: Increased unsaturation
It signifies the presence of double bonds in (higher iodine value) can improve fatty acid
fatty acids, the more unsaturated fatty acid. digestibility, especially in partially
hydrogenated fats.

4. Free fatty acids

FFAs are released from triglycerides (fats and oils) through hydrolysis, a process often accelerated
by lipase enzymes.
Significance:

Pharmaceutical Therapeutic

Impact on Quality :A lower level of free fatty High levels of free fatty acids (FFAs) in ) in
acids (FFAs) in sneha indicates a higher "sneha" are associated with several health
quality and increased stability of the issues, including insulin resistance, type 2
diabetes, obesity, and cardiovascular disease.
 substance. This suggests a reduced risk of
rancidity and a longer shelf life.

5. Refractive index
 Definition : Refractive index is the ratio of the speed of light in a vacuum to its speed in a
given substance. It's a physical property that helps identify a substance and assess its purity.
Significance:
 Identify the Sneha: Different oils and fats have specific refractive index values.
Deviations from the standard refractive index can indicate adulteration or improper
preparation.
 Determine purity: Monitor the process: Changes in refractive index during Sneha
preparation (Sneha Paka) can indicate the progress of the process and the incorporation of
active ingredients from the other ingredients.
 Assess quality: A stable refractive index within the standard range indicates a well-
prepared and stable Sneha.

6. High performance thin layer chromatography

It can be a valuable tool for analyzing the chemical composition and quality of Sneha Kalpana
preparations.
Significance:
Identifying Active Compounds
Quantifying Active Compounds
Stability Studies : HPTLC can be used to assess the stability of Sneha Kalpana over time by
monitoring changes in the concentration of active compounds.
Quality Control: HPTLC can help ensure that the Sneha Kalpana meets specific quality standards
by verifying the presence and quantity of desired compounds.
Detection of Adulterants : HPTLC can be used to detect the presence of any adulterants or
contaminants in Sneha Kalpana, ensuring the purity and safety of the formulation.
[Link](Thin layer chromatography)
TLC helps in identifying and quantifying the active components within these preparations,
ensuring their quality, safety, and efficacy.
Significance:
Evaluating Snehapaka : TLC can be used to evaluate the Snehapaka (the process of preparing
Sneha Kalpana), particularly in assessing the stability of the oil and the extraction of active
components.
Monitoring Rancidity: TLC can detect rancidity in Sneha Kalpana by identifying the breakdown
products of fats and oils.
Assessing the Presence of Aflatoxins: TLC can be used to screen for the presence of aflatoxins,
which are toxic compounds that can contaminate plant-based materials.

8. Peroxide value
The peroxide value is defined as the amount of peroxide oxygen per 1 kilogram of fat or oil.
Significance:
High peroxide values signify increased rancidity and potential instability, while low values
suggest a more stable and pure product.
It reflects the extent of oxidation, which is a major factor in the deterioration of fats and oils,
leading to off-flavors and off-odors.
Quality Assessment : Peroxide value helps in determining the purity and stability of Sneha
Kalpana.
Shelf Life Prediction : Higher peroxide values indicate a shorter shelf life due to increased
rancidity.

[Link] of Rancidity(Kries)
Rancidity refers to the spoilage of fats and oils, resulting in unpleasant odors, tastes, and potentially
harmful byproducts.
Causes: Rancidity in Sneha Kalpana is primarily due to oxidation and hydrolysis of the fatty acids
in the oils and ghee.
Rancidity: Can Alter the sensory properties (odor and taste) of the formulation.
Reduce the therapeutic efficacy of the Sneha Kalpana by degrading active compounds.
Shorten the shelf life of the product.
Potentially lead to the formation of harmful compounds.

Ayurvedic Perspectives on Rancidity:

 Sneha Siddhi Lakshana : Ayurveda emphasizes the importance of "Sneha Siddhi
Lakshana," which refers to the criteria for judging the proper preparation of medicated oils
and ghee.
 Murchana Samskara: Murchana, a process of purifying and stabilizing Sneha, is
believed to decrease the acid value (an indicator of rancidity) and increase the
saponification value (a measure of the oil's ability to form soap),
 Amadoshaharati: The concept of "Amadoshaharati" (removal of Ama, or toxins) is also
linked to rancidity, as Ama can be correlated with moisture content and its removal can
help prevent spoilage.
 Durgandham Vinihanthi:Another principle, "Durgandham Vinihanthi," indicates the
removal of bad odors associated with rancid oils.
[Link]
While pH is not directly involved in the process, it is considered along with other parameters to
evaluate the quality of the final medicated oil or ghee.

 11. Viscosity
It refers to Measure of fluids resistance to flow the difference in the rate of flow is
attributed to the phenomenon called viscosity.
 Viscosity, in the context of Sneha Kalpana, refers to the resistance of the medicated oil or
ghee to flow, indicating its consistency.
 Significance:
 It's a vital parameter for assessing the quality and purity of Sneha preparations.
 Stability and Efficacy: Viscosity changes can indicate potential issues like rancidity or
improper processing, which can affect the stability and therapeutic effectiveness of the
Sneha
 Influence of Processing: The Sneha Murchchhana process, a pre-treatment step in Sneha
preparation, can affect the viscosity of the final product.

Parameters of various Ghritha and Taila in API.

Parameters Range

Refractive index 1.43-1.53

Weight per ml at 40 0.829-0.985

Saponification Value 180-225

Iodine Value 30-100

Acid Value 2-6

Peroxide Value 1-10

CONCLUSION
 The need for the quality control methods for the Ayurvedic drugs is must due to
commercialization of the Ayurvedic pharmacies.
 Inclusion of the Ayurvedic drugs under the Drugs and Cosmetic Act.
 Data obtained from the above parameters may be used to fix the standards for the
formulations of Sneha (Ghrita/Taila).
 This fixation of different standards will be ultimately helpful to standardize Sneha kalpana.
 Similarly quality control parameters has to be applied for different formulations.
Factors Contributing to Quality Differences
The growing intricacy of contemporary pharmaceutical production, driven by a diverse array of
specialized drugs and dosage formats, has introduced multifaceted ethical, legal, and financial
obligations for those involved in manufacturing. It is essential for everyone engaged in the creation,
oversight, and promotion of pharmaceutical products to recognize and understand these critical
responsibilities to ensure high-quality outcomes.
 Factors Influencing Product Quality
Factors Influencing Product Quality Several key elements can impact the final quality of a product:

 Quality of raw materials used

 Variations occurring during the production process

 Characteristics of packaging materials

 Accuracy and clarity of labeling

 Condition of the finished product

 Human errors during handling or assembly

QA Department Responsibilities

 The QA team ensures strict adherence to the company's established quality policies.

 It plays a crucial role in developing and maintaining Standard Operating Procedures

(SOPs) that govern quality control processes.

 The department verifies that products comply with all relevant specifications and
confirms they are produced in line with internal Good Manufacturing Practice (GMP)
standards.

 Additionally, QA oversees ongoing quality surveillance and conducts audits to uphold

product integrity.

 The Quality Assurance team continuously monitors processes to ensure they meet all
relevant internal standards and external regulations.
 They provide expert advice and direction to help operations achieve and maintain full
compliance at all times.

Quality Control Responsibilities

 Quality Control (QC) oversees the daily management of quality standards throughout the
organization.

 This team handles the analytical evaluation of all incoming raw materials and carefully
inspects packaging elements, including labels.
 They perform testing during production as needed, carry out environmental surveillance,
and ensure all processes comply with established regulations.

 Additionally, QC is tasked with conducting the necessary tests on the final

pharmaceutical products before release.

 Quality Control is instrumental in identifying and approving reliable vendors for raw
material procurement. This involves rigorous testing of sample batches and often
requires a thorough audit of the vendor’s processes to assess their adherence to Good
Manufacturing Practices (GMP) before granting approval.

 The QC team also conducts regular inspections and testing of the environmental
conditions within manufacturing areas where different dosage forms are produced,
ensuring compliance with required standards.

PACKAGING AND LABELLING

INTRODUCTION

 Packaging is the science, art and technology of enclosing or protecting products for
distribution, storage, sale, and use.

 Packaging also refers to the process of design, evaluation, and production of packages.

 Pharmaceutical packaging can be defined as the economical means of providing

presentation, protection, identification, information, convenience ,compliance, integrity
and stability of the product.

FUNCTIONS OF PACKAGING

 Product Identification:- Packaging greatly helps in identification of products.

 Product Protection:- Packaging protects the contents of a product from spoilage,
breakage, leakage, etc.
 Facilitating the use of product:- Packaging should be convenience to open, handle and
use for the consumers.
 Product Promotion:- Packaging is also used for promotional and attracting the attention
of the people while purchasing.

TYPES OF PACKAGING
1]Primary packaging- is the material that first envelops the product and hold it. This usually
is the smallest unit of distribution or use.
Ex. Acrosol spray can, blister packs, bottle
2[Secondary packaging -
Is outside the primary packaging perhaps used to group primary package together.
Ex. Boxes, cartons
3]Tertiary packaging- is used to bulk handling and shipping.
Ex. Barrel, container, edge protector

PACKAGE TESTING
 Drop test
 Vibration test
 Shock test
 Inclined impact test
 Revolving drum test

TYPES OF PACKAGING MATERIALS USED FOR PHARMACEUTICAL

PACKAGING
Glass
Plastics
Rubbers
Paper/card boards
Metals

THE CHOICE OF PACKAGING MATERIAL WILL DEPEND UPON:

 The degree of protection required

 Compatibility with the dosage form

 Customer convenience c.g. size, weight of dosage form,

 Filling method

 Sterilization method to be employed and cost

Ideal packaging requirements

[Link] must protect the preparation from environmental conditions.

2. They must not be reactive with the product.

3. They must not impart to the product tastes or odors.

4. They must be nontoxic.

 5. They must be FDA approved.

6. They must meet applicable tamper-resistance requirements.

7. They must not be the cause of product degradation.

[Link] must be adaptable to commonly employed high speed packaging equipment.

Hazards encountered by package

Hazards encountered by the package can be divided into three main groups.

a) Mechanical hazards

b) Climatic or environmental hazards

c) Biological hazards.

The only exception is theft, which can be a serious risk with drugs and may demand special
protection in certain cases.

a) Mechanical hazards: 1. Shocking or impact damage

2. Compression

3. Vibration

4. Electrical conductance

5. Abrasion

b) Climatic or environmental hazards:

1. Moisture

2. Temperature

3. Pressure

4. Atmospheric gases

5Light
[Link] airborne contaminants.

c) Biological hazards.

[Link] hazards

2. Chemical hazards

GLASS:

Glass has been widely used as a drug packaging material

Advantages

 They are transparent.

 They have good protection power.

 They can be easily labelled.

 Economical

 Variety of sizes and shapes

Disadvantages
 Glass is fragile so easily broken.
 Release alkali to aqueous preparation

COMPOSITION OF GLASS

 Sand (silicon dioxide) Soda ash (sodium carbonate) Limestone (calcium carbonate) Cullet
(broken glass) - aluminium, boron, potassium, magnesium, zinc, barium,

 Amber: light yellowish to deep reddish brown, carbon and sulphur or iron and manganese
dioxide

 Yellow: Compounds of cadmium and sulphur

 Blue: Various shades of blue, cobalt oxide or occasionally copper (cupric) oxide

 Green: iron oxide, manganese dioxide and chromium dioxide

PLASTIC

Plastics may be defined as any group of substances, of natural or synthetic origins, consisting
chiefly of polymers of high molecular weight that can be moulded into a shape or form by heat
and pressure.

Advantages

 Less weight than glass,

 flexible

 Variety of sizes and shapes

 Essentially chemically inert, strong, rigid Safety use, high quality. various designs

 Extremely resistant to breakage

Disadvantages

 Absorption permeable to moisture

 Poor printing, thermostatic charge

TYPES OF PLASTICS

Thermosetting type-

When heated they may become flexible but they do not become liquid

e.g. Urea formaldehyde (UF), Phenol formaldehyde, Melamine formaldehyde (MF), Epoxy
resins (epoxides), Polyurethanes (PURs)

Thermoplastics type-

On heating they are soften to viscous fluid which harden again on cooling.

c.g. Polyethylene (HDPE-LDPE).

Polyvinylchloride(PVC), Polystyrene Polypropylene, Nylon(PA), Polyethylene terepthalate

(PET) Polyvinylidene chloride(PVdC), Polycarbonate Acrylonitrile butadiene styrene (ABS)

METALS:
Metals are used for construction of containers. The metals commonly used for this purpose are
aluminium, tin plated steel, stainless steel, tin and lead

Advantages:

 They are impermeable to light, moisture and gases.

 They are made into rigid unbreakable containers by impact extrusion.

 They are light in weight compared to glass containers.

 Labels can printed directly on to their surface.

Disadvantages:

 They are expensive.

 They react with certain chemicals

RUBBER:

Rubber is used mainly for the construction of closure meant for vials, transfusion fluid bottles,
dropping bottles and as washers in many other types of product.

BUTYL RUBBER:

Advantages:

 Permeability to water vapour.

 Water absorption is very low.

 They are relatively cheaper compared to other synthetic rubbers.

 Disadvantages:

 Slow decomposition takes place above 130-C.

 Oil and solvent resistance is not very good.

NITRILE RUBBER:
Advantages: Oil resistant due to polar nitrile group Heat resistant.

Disadvantages:

Absorption of bactericide and leaching of extractives are considerable.

CHLOROPRENE RUBBERS:
Advantages: Oil resistant, hest stability is good.

SILICON RUBBERS:

Advantages:

 Heat resistance.

 Extremely low absorption and permeability of water.

 Excellent aging characteristic.

Disadvantages:

 They are very expensive.

TAMPER RESISTANT PACKAGING:

 The requirement for tamper resistant packaging is now one of the major considerations in
the development of packaging for pharmaceutical products.

 Tamper resistant package is one having an indicator to entry in which, if missing, can
reasonably be expected to provide visible evidence to consumers that tampering has
occurred.

 FDA approves the following configurations as tamper resistant packaging: Film wrappers,
Blister package, Strip package, Bubble pack, Shrink seals, and bands Oil, paper, plastic
pouches, Bottle seals, Tape seals, Breakable caps, Aerosol containers

Film wrapper

 Film wrapping has been used extensively over the years for products requiring package
integrity or environmental protection.

 It is categorizes into following types:

 End folded wrapper

 Fin seal wrapper

 Shrink wrapper

 End folded wrapper

 The end folded wrapper is formed by passing the product into a sheet of over wrapping
film, which forms the film around the product and folds the edges in a gift wrap fashion.

 The folded areas are sealed by pressing against a heated bar. The materials commonly used
for this purpose are cellophane and polypropylene.

Fin seal wrapper

 The seals are formed by crimping the film together and sealing together the two inside
surfaces of the film, producing a fin seal.

 Fin sealing is superior than end folded wrapper With good seal integrity the over wrap can
removed or opened by tearing the wrapper

 Shrink wrapper

 The shrink wrap concept involves the packaging of the product in a thermoplastic film that
has been stretched and oriented during its manufacture.

 An L shaped sealer seals the over wrap

 The major advantage of this type of wrapper are the flexibility and low cost of packaging
equipment.

BLISTER PACKAGE:

 Blister package provides excellent environmental protection, and efficacious appearance.

 It also provides user functionality in terms of convenience, child resistance and tamper
resistance

 The blister package is formed by heat softening a sheet of thermoplastic resin and vacuum
drawing the soften sheet of plastic into a contoured mold.
 After cooling the sheet is released from the mold and proceeds to the filling station of the
machine. It is then lidded with heat sealable backing material

 Peel able backing material is used to meet the requirements of child resistance packaging.

 The material such as polyester or paper is used as a component of backing lamination.

 Materials commonly used for the thermo formable blister are PVC, polyethylene
combinations, polystyrene and polypropylene.

STRIP PACKAGE

 A strip package is a form of unit dose packaging that is commonly used for the packaging
of tablets and capsule.

 A strip package is formed by feeding two webs of a heat sealable flexible through heated
crimping roller.

 The product is dropped into the pocket formed prior to forming the final set of seals. A
continuous strip of packets is formed in general.

 The strip of packets is cut into desired number of packets.

 Different packaging materials used are: paper/polyethylene/foil/PVC,

BOTTLE SEALS

 A bottle may be made tamper resistant by bonding and inner seal to the rim of the bottle in
such a way that the product can only be attained by destroying the seal.

 Typically glassine liners are two ply laminations use in two sheet of glassine paper
bounded together with wax or adhesive

 For pressure sensitive inner seals pressure sensitive adhesive is coated on the surface of
the inner seal as an encapsulated adhesive.

TAPE SEALS

It involves the application of glued or pressure sensitive tape or label around or over the closure
of the package which is to be destroyed to obtain the product.

The paper used must often is a high density light weight paper with poor tear strength.
BREAKABLE CAPS

Breakable closures come in many different designs.

The roll-on cap design of aluminium shell used for carbonated beverages.

The bottom portion of the cap is rolled around the bottle neck finish.

The lower portion of the cap blank is usually perforated so that it breaks away when the cap is
unscrewed. The bottom portion of the closure has a tear away strip.

SEALED TUBES

Collapsible tubes used for packaging are constructed of metal, plastic or lamination of foil,
paper and plastic.

Metal tubes are still used for products that required high degree of barrier protection

Most of these are made of aluminum.

Extruded plastic tubes are widely used for products that are compactable and limited protection
of plastic.

LABELLING

Introduction

Label means a display of written, printed or graphic matter upon immediate container or the
wrapper of a drug package

The term "labeling" designates all labels and other written, printed, or graphic matter upon an
immediate container of an article or upon, or in, any package or wrapper in which it is outer
shipping enclosed, containerlil except any

Labeling in India

 All labels of a drug should conform as per the specifications under the Drugs and
Cosmetics Rules 1945.

o That no person sell or distribute any drug unless it is labeled in accordance with
the Rules (Rule 95 of D&C Act).
 o it includes information regarding

 -indications, effects, dosage form, frequency and duration of administration, warnings,

hazards, contraindications, side effects, precautions and other relevant information.

Functions of Label

 For identification of the product

 Provide ingredients

 Purpose/use of the product

 Child safety

 Other information like maximum retail price(MRP), Batch No., Shelf-life etc

DEFINITION OF LABEL:
"Label means a display of written, printed or graphic matter upon immediate container or the
wrapper of a drug package"

Objective of Labeling
The Food and Drug Administration (FDA) requires that drug labeling be balanced and not
misleading. The label must be scientifically accurate and provide clear instruction to health
care practitioners for prescription drugs and to consumers for over-the-counter drugs and
supplements. Labeling regulations require that the statement of ingredients must include all
ingredients, in the order in which they are used in the drug.

1. Brand identification
Labeling helps in the identification and principal place of business of the person by or for whom
the prepackaged product was manufactured, processed, produced or packaged for resale.

2. Description
Labels provide the information regarding the pharmaceuticals. It describes the composition,
batch no., cost, manufacturing date, expiry date etc.

3. Promotion
Finally labels helps in promoting the product through attractive and bright graphics replacing
paper labels glued on bottles.

[Link] differentiate Standard and Counterfeit drugs A counterfeit drug bears an unauthorized
representation of a registered trademark on a product identical or similar to one for which the
trademark is registered.
The use of scratch off label containing a unique code can be done which if texted to a free no.
provides a response from company server, which will assure the authenticity of product.

The use of unique holograms and designs in labels, which can not be easily copied.

Importance of Labeling
The safe use of all medicines depends on users reading the labeling and packaging carefully
and accurately and being able to assimilate and act on the information presented.

All labels must be clear and concise and must bear all necessary information regarding the safe
use of a product.

TYPES OF LABEL
[Link] label

[Link] label

[Link] label
 A label which contain drug information for the use of medical practitioners,
pharmacists, or nurses supplied by the manufacturer, packer, or distributor of the drug.
 Rule 96 of the Drug and Cosmetic Rules (manner of labelling) mandates the minimum
information which needs to be put on the label of all medicines.

LEGAL REQUIRMENTS OF A MANUFACTURER LABEL

1. The name of preparation

2. Strength and dosage form.

3. Quantity.

4. Instructions for the use.

5. Precautions & warnings.

6. Registration number.

7. Batch number.
8. Manufacturing & Expiry date.

9. Price

10. The name and address of pharmaceutical industry

[Link] OF THE PREPARATION

Generic name:
According to drug labelling and packaging rules 1986:
"International non-proprietary name means the name of a drug as recommended by WHO or
may be notified by the federal govt. in the official gazete"

Brand Name:
Brand name which is used to market the drug

Property of drug company

[Link] AND DOSAGE FORM

STRENGTH
It is amount of active drug per unit dose.

Example: amoxicillin 250mg capsules and amoxicillin 500mg capsules

DOSAGE FORM
Dosage form of the medicine should be mentioned on the label. e.g.,
Different dosage forms of Amoxicillin

[Link]
Quantity/volume present per a packaging unit

4. INSTRUCTIONS FOR USE

 KEEP IN REFRIGERATOR
 SHAKE WELL BEFORE USING
 GIVE WITH FOOD
 KEEP REFRIGERATED

Medication Instruction Labels

Shake well before use:

Necessary on all disperse systems:

Emusions

Suspensions e.g..Liniments ,Lotions Tinctures

5. Precautions & warnings.

Warning!!!!!

DO NOT SHAKE THE PATIENT, SHAKE THE BOTTLE WELL BEFORE USE.......

6. Registration number.
Registration number"A number given to a specific drug when it is registered according
to specific rules by registration board set up by federal government"
7. Batch number.
Acc. to drug act 1976
"A designation printed on label of a drug that identifies the batch and permits the production
history of the batch including all stages of manufacturer and control to be traced and are
viewed"

8. Manufacturing & Expiry date.

Expiry date

Accorrding to drug act 1976 S 3

"Date stated on the label of a drug after which a drug is not expected to retain its claimed
efficacy, safety, quantity, or potency or after which it is no permissible to sell the drug"

9. Price:
Price of the drug should mentioned

10. The name and address of pharmaceutical industry

The name of pharmaceutical industry should be specified .

[Link] label
All dispensed medicines should ideally be provided with a label, which clearly states:

(i) Name of the patient

(ii) Name, strength, batch number and expiry of the medicine, in case the medicine has been
repacked or cut out from a larger pack
(iii) Dosage and usage instructions

(iv) Date of delivery

(v) Storage instructions

(vi) Name and address of the pharmacy

Packaging Insert
The Package insert is considered "adequate direction for use", [1]

The main aim of the package inserts or leaflets is to provide information essential for the
safe and effective use of the drugs, and hence reducing the number of adverse reactions
resulting from medication errors.

In India, regulations for package insert are provided under 'Section 6.2' and 'Section 6.3' of
Drugs and Cosmetics Act (1940) and Rules (1945).
 1. Kalam A, Anwar 5, Fatima A, "Drug Package Inserts In India: Current
Scenario", World Journal of Pharmacy And Pharmaceutical Sciences, Mar 2014,
3(4), 385-392

[Link] of Packaging Insert [5]:

 Sec 6.2 Therapeutic Information

 Sec 6.3 Pharmaceutical Information
 Posology and method of administration
 Contra-indications.
 Special warnings and special precautions for use, if any.
 Interaction with other medicaments and other forms of interaction.
 Pregnancy and lactation, if contra-indicated.
 Effects on ability to drive and use machines, if contra-Indicated.
 Undesirable effects/side effects.
 Antidote for overdosing
 List of excipients
 Incompatibilities
 Shelf life in the medical product as packaged for sale.
 Shelf life after dilution or reconstitution according to direction.
 Shelf life after first opening the container.
 Special precautions for storage.
 Natura and specification of the container.

Machinery Employed
Labeling machines are machines that dispense, apply or print-and-apply labels to various items,
products, containers, or packages

Labeling equipment are various machines, including label printers, label applicators, printer-
applicators, and labeling systems, that apply labels to various products and packages.

Types of Labeling machinery

1. Semi Automatic Labeling Machine

2. Fully Automatic Labeling Machine :

i. Fully Automatic Single Side Sticker Labeling

Machine
ii. Fully Automatic Double Side (front & back)
Sticker Labeling Machines
iii. Fully Automatic High Speed Sticker Labeling
Machine
[Link] Automatic Labeling Machine
 Semi Automatic Labelling Machine are suitable for labelling on Round Vials,
Bottles.
 No change of parts is required for change in size of containers & labels suitable for
Glass, Plastic, Composite Containers can be prepared.
 Grooved and Brut Shaped Bottles can also be labeled.
 The Semi Automatic Labelling incorporates latest sophisticated. Machine
 Microprocessor Controlled Stepper Motor Drive, Fiber Optic Label and Container
sensing system.

[Link] Automatic Labeling Machine

 Fully Automatic Labelling machine is useful to place label accurately on round
shape of product.
 Full or partial wrap labeling can be possible.
 A unique feature of machine is if the body diameters changes, than also machine
operates without change in part.
 Products of different diameter like small size of vials and bottles upto containers
can be accommodated in the same machine & Speed is depend on the length of
label.

 Different types such as Alluminium, Glass, Plastic products can be accommodated on

the machine.
 Labeling speed is automatically synchronized with conveyor speed to ensure quality.
 Push and press optional attachment is used to ensure smooth labeling without wrinkles
or bubble.
New Developments in Labeling Technology
to Pharmaceutical labelling is more complex than ever, with increasing pressure from
consumers and regulatory bodies prevent counterfeiting and improve safety.
Manufacturers and packaging companies need to ensure products can be recognized
and verified quickly and easily throughout the supply chain, communicating vital
information to retailers and distributors.

Today's drug manufacturers can choose from a wide selection of:

Automatic Identification and Data Capture (AIDC) technologies

Radio Frequency Identification (RFID) tags

 For instance, using AIDC technologies, manufacturers can include product or
batch specific data in individual product labels. In the pharma industry, this
could enable suppliers and retailers to verify a product quickly and accurately
in most cases using standard technology.
  RFID tags can be read without the need for close contact or a direct line of sight,
and offer read/write functionality, which makes them ideal for tracking products
and monitoring processes. However, relatively high cost and complexity of
implementing the technology has prevented its progress in many areas, incl
including the pharma industry.
2D Barcodes:
 2D barcodes can hold considerably more information than standard barcodes
(usually up to approximately 1000 characters of information on a single label)
making them better suited to meet the requirements of today's manufacturers.
 This increased level of information can be held on a label the same size or
smaller than a conventional barcode label, and the codes can, in most cases, be
printed using the same technology, helping to minimize the cost of upgrading.
 Furthermore, 2D barcodes can also function as a database themselves, providing
a portable information source on the labelled product.

PORTABILITY AND STORAGE :

PORTABILITY:
The "portability" of pharmaceutical products refers to how easily they can be moved and used
in different locations, encompassing packaging design for user convenience (like sachets) and
logistical challenges in transport (such as temperature control). It also includes the process
portability of manufacturing, enabling a process to be moved between facilities to enhance
supply chain resilience.

Product Portability (User-Focused)

Packaging:
Products are made more portable through innovative packaging like sachets, which are
compact, easy to carry, and convenient for administering medicine on the go.

Design:
This user-focused portability caters to the needs of modern consumers who require on-the-go
health management solutions.

Logistical Portability (Supply Chain-Focused)

Transport Conditions:
Pharmaceutical products require specific and carefully controlled transport conditions,
including temperature and humidity control.

Packaging for Transport:

This involves using specialized packaging like refrigerated containers or Styrofoam palettes
with ice packs to maintain product integrity during transit.
Record Keeping:
Detailed records of the entire journey, including temperature fluctuations and delays, are
essential for traceability and regulatory compliance.

Process Portability (Manufacturing-Focused)

Manufacturing Movement:
This is the ability to move a pharmaceutical product's manufacturing process between different
facilities or locations without compromising quality or efficiency.

Supply Chain Resilience:

Process portability is a key strategic framework for protecting pharmaceutical operations from
disruptions and ensuring continuity of supply.

Technology Transfer:
The underlying concept of transferring knowledge and processes from R&D to manufacturing
or between different manufacturing sites is central to achieving process portability.

DRUG STORAGE,
Proper storage of medication is always an important consideration during periods of extreme
heat or cold. Drugs can undergo physical, chemical & microbial changes on storage.

Recommended storage conditions:

 Store below -5°C (freeze)

 Store between (2 to 8) C (refrigerate, do not freeze)
 Store below 25° C (air conditioning)
 Store below 30°C (room temperature)

DRUG STORAGE
Drug Storage Room Standards:
 A lockable room
 Adequate lighting
 A temperature of below 25°C, with air conditioning units that operate 24 hrs per
day & are connected to an emergency power supply.
 A vaccine refrigerator for storage of vaccines & anti-venom.
 A nominated refrigerator for cold storage of pharmaceutical products that requires
refrigeration.
 Adequate shelving for appropriate storage of the different categories of drugs.
 DRUG STORAGE
All drugs are grouped in the following categories

Refrigerated (Heat sensitive products)

Oral (solid & liquid)

- Injectable

-Topical

- Infusion

- Inhalation
- Non Drug

DRUG STORAGE
In the Central pharmacy or Pharmacy main store, all drugs are displayed or kept in
different ways regarding the most easiest way to dispense.

Like-

Alphabetically

Therapeutic class wise

Brand wise and so on.

DRUG STORAGE
 To uphold quality standards in drug storage room:
 Rotate stock so that the stock closest to expiry date is kept in front.
 Maintain FEFO / FIFO/LIFO procedure.
 Make sure that there is no expired drugs on the shelves

DRUG STORAGE
First-expiry/first-out procedure(FEFO)

First-in/first-out procedure (FIFO)

Last-in/first-out procedure (LIFO)

UNIT -5 BIOPHARMACEUTICS
5.1 BIOPHARMACEUTICS AND PHARMOKINETICS
BIOPHARMACEUTICS:
Introduction to Biopharmaceutics:
 Biopharmaceutics:thestudyofhowthephysicochemicalpropertiesofdrugs,dosageformsandrou
tesofadministerationaffecttherateandextentofthedrugabsorption.

Thus,biopharmaceutics involves factors that influencethe:

1)protection and stability of the drug within the product;

2)the rate of drug release from the product;

3)the rate of dissolution of the drug at the absorption site ; and

4)the availability of the drug at its site of action.

Scheme demonstrating the dynamic relationships among the drug, the product, and
pharmacologic effect.

ADME: is an acronym in pharmacokinetics and pharmacology for absorption, distribution,

metabolism, and excretion, and describes the disposition of a pharmaceutical compound within
an organism.

Pharmacokinetics:The study and characterization of the time course(kinetics)of drug

absorption, distribution, metabolism and elimination(ADME).

Absorption: is the process of a substance entering the body.

Distribution: is the dispersion of substances throughout the fluids and tissues of the body.

Metabolism: is the irreversible transformation of parent compounds into daughter

metabolites.

Excretion: is the elimination of the substances from the body

Bioavailability: The rate and extent of drug absorption.

Bioavailabledose: The fraction of an administered dose of a particular drug that reaches the
systemic circulation intact.

Absorption

Main factors affecting oral absorption:

I Physiological factors.

II Physical-chemical factors.

III Formulation factors.

I Physiological factors affecting oral absorption:

1-Membrane physiology.

2-Passage of drugs across membranes.

3-Gastrointestinal physiology.

I. Characteristics of GIT physiology and drug absorption

II. Gastric emptying time and motility

III. Effect of food on drug absorption

1-Membrane physiology (Cont.):
-The cell membrane is the barrier that separates the inside of the cell from the outside.

-The cell membrane is made up of phospholipids, proteins, and other macromolecules.

-The phosopho lipids make up a bilayer. It contains hydrophilic and hydrophobic molecules.

-The proteins in the cell membrane are located within the phospholipid bilayer.

-So,the biologic membrane is mainly lipid in nature but contains small aqueous channels or
pores

2-Passage of drugs across membranes:

3-Gastrointestinal (GI) Physiology:

-The gastro intestinal tract is a muscular tube approximately 6 min length with varying
diameters.

-It stretches from the mouth to the anus and consists of four main anatomical areas:the
oesophagus, the stomach, the small intestine and the large intestine or colon.

-The majority of the gastrointestinal epithelium is covered by a layer of mucous. This is a

viscoelastic translucent aqueous gel that is secreted throughout theGIT, acting as a protective
layer and a mechanical barrier.

Distribution: Drugdistribution :means the reversible transfer of drug from one location to
another within the body.

-The distribution of drugs in the body depends on:

1-their lipophilicity

2-protein binding.

Low plasma binding or high tissue binding or high lipophilicity usually means an extensive
tissue distribution
Factors affecting drug distribution: Factors Affecting Distribution

A-Rate of distribution B-Extent of Distribution

[Link] permeability 1. Lipid Solubility
2. Blood perfusion 2. pH –pKa
3. Plasma protein binding
4. Tissue drug binding

[Link]

[Link]:
Capillary walls are quite permeable.

Lipid soluble drugs pass through very rapidly.

Water soluble compounds penetrate more slowly at a rate more dependent on their size.

Low molecular weight drugs pass through by simple diffusion. For compounds with
molecular diameter above100Å transfer is slow.
For drugs which can be ionized the drug'sp Kaand thepH of the blood will have a large effect
on the transfer rate across the capillary membrane

2. Blood perfusion rate:

The rate at which

Blood perfuses to

Different organs varies widely

The rate at which a drug reaches different organs and tissues will depend on the blood flow to
those regions.

-Equilibration is rapidly achieved with heart, lungs,l

iver, kidneys and brain where blood flow is high.

-Skin,bone,and depot fat equilibrate much more slowly

[Link]

[Link] Solubility:
-Lipid solubility will affect the ability of the drug to bind to plasma proteins and to cross lipid
membrane barriers.
-Very high lipid solubility can result in a drug partitioning into highly vascular lipid-rich areas.
Subsequently these drugs slowly redistribute into body fat where they may remain for long
periods of time

[Link]:
-The rate of movement of a drug out of circulation will depend on its degree of ionization and
therefore its pKa.

-Changes in pH occurring in disease may also affect drug distribution. For example, blood
becomes more acidic if respiration is inadequate.

[Link]:
-Extensive plasma protein binding will cause more drug to stay in the central blood
compartment. Therefore drugs which bind

Strongly to plasma protein tend to have lower volumes of distribution.(↑protein binding=↓V)

Drug metabolism:
Metabolism is defined as: The irreversible biotransformation of drug in the body →
typically involves making it more polar to enhance renal excretion
-Drug metabolism often converts lipophilic chemical compounds into:

more hydrophilic, more water soluble

have their actions decreased (become less effective) or increased (become more effective)

May be converted to less toxic or more toxic metabolites or to metabolites with different type
of effect or toxicity

-
Themetabolismofdrugstakesplacemainlyintheliver(thesmoothendoplasmicreticulumoftheliver
cell).However, other organs such as the kidney, lung, intestine and placenta can also be
involved in this process.
Occasionallythemetaboliteislesswatersoluble.

-A significant example is the acetyl metabolite of some of the sulfonamides.

-Some of the earlier sulfonamides are acetyl at edtorelatively insoluble metabolites which
precipitate dinurine, crystalluria.

-Now the more commonly used sulfonamides have different elimination and solubility
properties and exhibit less problems
Two types of Metabolic Reactions
Phases of metabolism
Factors that can influence drug metabolism:
[Link]: Drugs metabolism is slower in fetal, neonatal and elderly humans than in adults.

[Link]: women metabolize alcohol more slowly than men

[Link]: Certaindrugs(enzymeinducers) can increase the rate of metabolism of active

drugs(enzymeinduction) and thus decrease the duration and intensity of the their action. The
opposite is also true (enzyme inhibition).

[Link]: Grape fruit juice contains furanocoumarins which inhibit drug metabolism by
interfering with hepatic cytochromeP450.

[Link](polymorphism):
With Nacetyltransferases(involvedinPhaseIIreactions), individual variation creates a group of
people who acetylatedrugs (isoniazid) slowly (slowacetylators) and those who acetylate
quickly.

-This variation may have dramatic consequences, as the slow acetylators are more prone to
dose dependent toxicity.

-13%of Egyptians are slow acetylators. Warfarin(bleeding) and phenytoin(ataxia)are examples

[Link] that can influence drug metabolism include age, individual variation
(e.g., pharmaco genetics), enterohepatic circulation,

nutrition, intestinal flora, or sex differences.

[Link] can also influence drug metabolism, including liver, kidney, or heart
diseases.

Drug excretion:
[Link] excretion:-The major organ for theexcretion of drugs is the KIDNEY. The functional
unit of the kidney is the nephron in which there are three major processes to consider:

1) Passive glomerular filtration

2) Active tubular secretion

3) Passive tubular re-absorption

[Link] excretion:
Elimination of toxicants in the feces

Occurs from two processes: A-excretioninbile:

B-directintestinalexcretion:
[Link]:
The lung is the major organ of excretion for gaseous and volatile substances. Most of the
gaseous anesthetics are extensively eliminated in expired air.

[Link]:
Drug excretion into saliva appears to bedependent on pH partition and protein binding.

In some instances, salivary secretion is responsible for localized side effects. Forexample,
excretion of antibiotics may cause black hairy tongue, and gingival hyperplasia can be a side
effect of phenytoin.

[Link]:
-Iodine, bromine, benzoic acid, salicylic acid, lead, arsenic mercury, iron and alcohol are
examples of compounds that excreted in sweat.

5.2 Bioavailability and Bioequivalence:

Bioavailability:
 It is a measurement of the extent of a therapeutically active drug that reaches the
systemic circulation and is available at the site of action. Absolute bioavailability:
Absolute bioavailability compares the bioavailability (estimated as are a under the
curve, or AUC) of the active drug in systemic circulation following non-intravenous
administration (i.e., after oral, rectal, transdermal, sub cutaneous administration),with
the bioavailability of the same drug following intravenous administration.
 It is the fraction of the drug absorbed through non-intravenous administration compared
with the corresponding intravenous administration of the same
Relative bioavailability:
This measures the bioavailability (estimated as are a under the curve, or AUC) of a certain
drug when compared with another formulation of the same drug, usually an established
standard, or through administration via a different route.

Bioequivalence:
-means pharmaceutical equivalents or pharmaceutical alternatives whose rate and extent of
absorption do not show a significant difference when administered at the same molar dose of
the therapeutic moiety under similar experimental conditions.

-Bioequivalence studies are usually performed to compare the rate and/or extent of absorption
of a new drug product or a generic equivalent with that of a recognized standard.

Methods to Assess Bioavailability:

I. Dissolution at administration or absorption site:

Method of evaluation: Dissolution rate

Example: Invitro: water, buffer, artificial gastric fluid, artificial intestinal fluid, artificial saliva,
artificial rectal fluid.

[Link] drug in systemic circulation:

Method of evaluation:1. Blood level time profile

[Link] blood level

[Link] to reach peak
[Link] under blood level time curve
Example: In vivo: whole blood, plasma, serum

III. Pharmacologic effect:

Method of evaluation:[Link] of effect

[Link] of effect

[Link] of effect

Example: In vivo: discriminate measurement of pharmacologic effect (blood pressure, blood

sugar, blood coagulation time)

IV. Clinical response:

Methodofevaluation:[Link] clinical blind or double- blind study

[Link] clinical success or failure

Example: In vivo: evaluation of clinical responses

V. Elimination:
Method of evaluation:1. Cumulative amount of drug excreted

[Link] excretion rate

[Link] time of excretion

Example: In vivo: urine