Formulation Development
Presented by: Dhruv Bharada (222930290010),
Pratham Gajjar(222930290013),
Heni Halpati (222930290014)
Guided by: Dr. Kalpesh Patel (Assistant professor,
M. Pharm , PhD Pharmaceutics)
Subject: (BP814TT): Pharmaceutical product development
GOVERNMENT PHARMACY COLLEGE, SURAT
Table of content
1. Introduction
2. Objectives of Formulation Development
3. Pre-formulation Studies
4. Drug Substance (API) Characterization
5. Key parameters studied
6. Selection of Dosage Form
7. Selection of Excipients
8. Manufacturing Process Development
9. Evaluation of Formulation
10. Biopharmaceutics and Drug Release
11. Stability Studies
12. Types of stability studies
13. Regulatory Considerations
14. ICH Guidelines
15. Conclusion
1. Introduction
•Formulation development is the process of designing and optimizing a
pharmaceutical dosage form.
•It ensures safety, efficacy, quality, and stability of the drug product.
•It bridges the gap between drug discovery and commercial manufacturing.
•To Convert API (Active Pharmaceutical Ingredient) into a patient-acceptable
dosage form. [1]
3
Objectives of Formulation Development
• To achieve desired therapeutic effect
• To ensure accurate dose delivery
• To improve bioavailability
• To enhance patient compliance
• To ensure stability during shelf life
• To make product suitable for large-scale manufacturing [1]
4
Pre-formulation Studies
Pre-formulation studies are investigational studies carried out during early
drug development to evaluate the physical, chemical, and mechanical
properties of a drug substance (API) in order to design a safe, effective, stable,
and acceptable pharmaceutical dosage form.
Study of physical and chemical properties of API
Helps in selection of:
• Excipient
• Dosage form
• Manufacturing process [1]
5
Drug Substance (API) Characterization
•Physical Properties: Particle size, shape, bulk density, flowability, and
polymorphic form.
•Chemical Properties: Molecular weight, functional groups, pKa, solubility, and
stability.
•BCS Classification: Classifies drugs based on solubility and permeability (Class
I-IV) to guide formulation strategy.
•Degradation Pathways: Hydrolysis, oxidation, photodegradation - guides
stability strategy and packaging selection.
•Hygroscopicity: Moisture uptake tendency affects storage conditions and
excipient compatibility. [2]
6
Key parameters studied:
1. Solubility: The ability of a drug to dissolve in a solvent to form a uniform
solution.
2. pKa: The pH at which a drug is present equally in ionized and unionized
forms.
3. Partition coefficient: The ratio of drug concentration in oil to that in water,
indicating its lipophilicity.
4. Stability: The ability of a drug to maintain its chemical and physical
properties over time.
5. Particle size: The dimension of individual drug particles that affects
dissolution and absorption.
6. Polymorphism: The ability of a drug substance to exist in more than one
crystalline form.
7. Hygroscopicity: The tendency of a drug substance to absorb moisture from
the surrounding air. [1] 7
Selection of Dosage Form
Selection of dosage form depends upon:
• Nature of drug
• Route of administration
• Dose size
• Desired onset and duration of action
• Patient factors (age, compliance)
Common dosage forms:
• Tablets
• Capsules
• Syrups
• Suspensions
• Injections
• Ointments and creams
• Modified/controlled release system [1] 8
Selection of Excipients
Excipients are inactive substances added to a formulation to support
manufacturing, stability, appearance, and patient acceptability.
1. Diluents (e.g., Lactose)
• Diluents are substances added to increase the bulk of a dosage form.
• Used when the drug dose is very small.
• They improve tablet size, weight, and handling.
Examples:Lactose, Microcrystalline cellulose,Dicalcium phosphate
2. Binders (e.g., PVP)
• Binders are materials used to hold powder particles together.
• They give mechanical strength to tablets.
• Prevent tablet breakage and crumbling.
Examples:Polyvinyl pyrrolidone (PVP),Starch,Gelatin [1] 9
Selection of Excipients
3. Disintegrants (e.g., Starch)
• Disintegrants help tablets break down into smaller particles after
administration.
• This allows faster drug dissolution and absorption.
Examples: Starch, Sodium starch glycolate
4. Lubricants (e.g., Magnesium Stearate)
• Lubricants reduce friction between tablet and machine parts.
• They prevent sticking and picking during compression.
• Improve smooth tablet ejection from the die.
Examples:Magnesium stearate, Talc, Stearic acid
10
Selection of Excipients
5. Preservatives
• Preservatives prevent microbial growth in formulations.
• Commonly used in liquid and semisolid preparations.
• Increase product safety and shelf life.
Examples:Methyl paraben, Propyl paraben, Benzalkonium chloride
6. Sweeteners and Flavors
• Added to mask unpleasant taste and odor of drugs.
• Improve patient compliance, especially in children.
• Mostly used in oral liquid formulations.
Examples: Sweeteners: Sucrose, Aspartame, Saccharin
Flavors: Orange, Mint, Strawberry [1]
11
Selection of Excipients
7. Coating Agents
Coating agents are used to cover tablets.
Purposes include:
• Protect drug from moisture and light
• Mask taste and odor
• Improve appearance
• Modify drug release
Examples: Hydroxypropyl methylcellulose (HPMC), Ethyl cellulose,
Shellac [1]
12
Manufacturing Process Development
•Unit Operations: Mixing, granulation, compression, coating, and filling form the
core of solid dosage manufacturing.
•Granulation Methods: Wet granulation improves compressibility; dry
granulation used for moisture-sensitive drugs; direct compression for stable APIs.
•Scale-Up Considerations: Process parameters are optimized from lab to pilot to
commercial scale to ensure consistency.
•Process Analytical Technology (PAT): Real-time monitoring of critical process
parameters to ensure quality during manufacturing (ICH Q8).
•Quality by Design (QbD): Design Space is established to define acceptable
ranges of process variables that ensure product quality. [1,2]
13
Example- Dry granulation process
14
Example- wet granulation process
15
Evaluation of Formulation:
Evaluation of formulation involves quality control tests performed to
ensure that the pharmaceutical product is safe, effective, uniform, and of
acceptable quality.
Quality Control Tests
1. Appearance
Visual examination of the dosage form.
Checks color, shape, size, surface texture, and presence of defects.
Ensures product is aesthetically acceptable and free from cracks, spots, or
contamination.
16
Evaluation of Formulation:
2. Weight Variation
Determines uniformity of tablet or capsule weight.
Individual units are weighed and compared with average weight.
Ensures dose uniformity and compliance with pharmacopoeial limits.
3. Hardness
Measures the mechanical strength of tablets.
Indicates the tablet’s ability to withstand handling, packaging, and
transport.
Excessive hardness may delay disintegration, while low hardness causes
breakage.
17
Evaluation of Formulation:
4. Friability
Measures the tendency of tablets to crumble or break.
Tablets are rotated in a friabilator and weight loss is measured.
Acceptable limit: less than 1% weight loss.
5. Disintegration Time
Time required for a tablet to break into smaller particles in a liquid
medium.
Indicates how quickly the drug becomes available for dissolution.
Important for immediate-release formulations.
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Evaluation of Formulation:
6. Dissolution Studies
Measures the rate and extent of drug release from the dosage form.
Performed using dissolution apparatus in specified media.
Predicts in vivo drug availability and bioavailability.
7. Content Uniformity
Ensures each dosage unit contains the correct amount of active drug.
Individual units are analyzed for drug content.
Critical for low-dose drugs. [2]
19
Disintegration apparatus
[5]
20
Dissolution apparatus
[6]
21
Friability tester
[7]
22
Monsento (hardness)
[8]
23
Biopharmaceutics and Drug Release
•Dissolution Testing: Measures rate and extent of drug release from dosage form
in vitro; key quality control test (USP Apparatus I & II).
•Bioavailability: Fraction of drug that reaches systemic circulation; influenced by
solubility, permeability, and first-pass metabolism.
•Bioequivalence (BE): Generic products must demonstrate equivalent rate and
extent of absorption compared to the innovator product.
•In Vitro-In Vivo Correlation (IVIVC): Mathematical relationship between
dissolution profile and in vivo absorption; used for formulation optimization.
•Modified Release Formulations: Extended, delayed, and pulsatile release
systems designed to control drug release rate and site of absorption. [3]
24
Stability Studies
Stability studies are tests performed to determine how the quality of a
drug product changes with time under the influence of environmental
factors such as temperature, humidity, and light.
Purpose of Stability Studies
Stability studies help to determine:
• Shelf life of the drug product
• Expiry date
• Recommended storage conditions
• Packaging requirements [3]
25
Types of Stability Studies
1. Accelerated Stability Studies
Performed at high temperature and humidity.
Used to predict long-term stability in a shorter time.
Helps in early detection of degradation.
Typical conditions:
40°C ± 2°C / 75% RH ± 5%
Duration: 6 months
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Types of Stability Studies
2. Long-Term Stability Studies
Conducted under normal storage conditions.
Provides actual stability data.
Used to assign final shelf life.
Typical conditions:
25°C ± 2°C / 60% RH ± 5%
Duration: 12–24 months
27
Types of Stability Studies
3. Intermediate Stability Studies
Conducted when accelerated study results show significant change.
Conditions lie between long-term and accelerated studies.
Helps confirm product stability.
Typical conditions:
30°C ± 2°C / 65% RH ± 5%
Duration: 6–12 months [3]
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Regulatory Considerations
•IND Application: Investigational New Drug application filed before human
trials; includes formulation details, manufacturing, and safety data.
•NDA / ANDA: New Drug Application for innovator drugs; Abbreviated NDA for
generic drugs - both require complete CMC data.
•CMC Section: Chemistry, Manufacturing, and Controls section describes drug
substance, drug product, and control of excipients.
•ICH Guidelines: Q8 (Pharmaceutical Development), Q9 (Quality Risk
Management), Q10 (Quality System) govern formulation development.
•Post-Approval Changes: Any change in formulation, manufacturing site, or
process post-approval requires regulatory notification or prior approval (ICH
Q12). [3,4]
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ICH Guidelines [4]
Guideline Title
ICH Q1A(R2) Stability Testing of New Drug Substances and Products
ICH Q1B Stability Testing: Photostability Testing
ICH Q1C Stability Testing for New Dosage Forms
ICH Q1D Bracketing and Matrixing Designs for Stability Testing
ICH Q1E Evaluation for Stability Data
ICH Q2(R1) Validation of Analytical Procedures: Text and Methodology
ICH Q3A(R2) Impurities in New Drug Substances
ICH Q3B(R2) Impurities in New Drug Products
ICH Q3C(R8) Impurities: Guideline for Residual Solvents
ICH Q3D(R2) Guideline for Elemental Impurities
ICH Q6A Specifications: Test Procedures and Acceptance Criteria for Chemical Substances
ICH Q8(R2) Pharmaceutical Development
ICH Q9(R1) Quality Risk Management
ICH Q10 Pharmaceutical Quality System
ICH Q11 Development and Manufacture of Drug Substances
ICH Q12 Technical and Regulatory Considerations for Product Lifecycle Management
ICH M7(R2) Assessment and Control of DNA Reactive Impurities
ICH M9 Biopharmaceutics Classification System-based Biowaivers
Conclusion
• Formulation development is a critical step in pharmaceutical product
development.
• It ensures that the drug product is safe, effective, stable, and patient-
friendly.
• Proper formulation design improves therapeutic outcome and market
success.
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References
References
1. Lachman L., Lieberman H.A., Kanig J.L. The Theory and Practice of
Industrial Pharmacy
2. Aulton M.E. Pharmaceutics: The Science of Dosage Form Design
3. Remington The Science and Practice of Pharmacy
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THANK YOU
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