PHARMCEUTICAL PRODUCT DEVELOPMENT

EXCIPIENTS USE IN TABLETS

AND CAPSULES
Guided by:--
Dr. Kalpesh A. Patel ([Link] , phd)
Assistant Professor Pharmaceutics

Taskin Sindhi (222930290057)

Nidhi Sisangia (222930290058)
Darshan Sojitra (222930290059)
Semester 8
Government Pharmacy College , Surat , 395001
LIST OF CONTENTS:-

A) Introduction to tablet and capsule excipients.

B) Role of Excipients in Product Development.
C) Characteristics of Ideal Excipients.
D) Excipients use in Tablets
E) Excipients use in Capsules.
F) Modern Trends in Excipients.
 INTRODUCTION.
 Tablets and Capsules of different types represent collectively the predominant
type of dosage form. [1]
 Besides the active ingredient, tablets and capsules normally contain a series of
excipients that are included to control biopharmaceutical and other quality
attributes, as well as to aid the manufacturing of the them.[1]
 Tablet and capsule excipients are inactive (non-therapeutic) substances added
along with the active pharmaceutical ingredient (API) to prepare tablets and
capsules. They help in manufacturing, stability, drug release, and patient
acceptability. [1]
 A series of excipients are normally included in a tablet and capsule; their role is to
ensure that the tableting operation can run satisfactorily and that tablets and
capsules of specified quality are prepared.[1]
 ROLE OF EXCIPIENTS.
 Improving Flow Properties :- Good powder flow is essential for Uniform die
filling of tablets and Proper capsule filling. Excipients improve flow by reducing
friction and cohesion between particles. [2]
 Providing Bulk and Uniformity :- Most drugs are present in very small
quantities and cannot be compressed or filled alone. Excipients are added to
Increase tablet/capsule size, Ensure uniform distribution of drug and Improve dose
accuracy. [2]
 Promoting Disintegration :- After administration, tablets must break into small
particles for drug release. Disintegrants help by Swelling in contact with fluids,
Creating internal pressure and Accelerating tablet breakup. [2]
 Stability and Shelf Life Enhancement :- Excipients protect drugs from
Moisture, Oxidation, Light, Microbial growth and increase product shelf life. [2]
• Taste Masking and Patient Acceptability :- Some drugs have bitter taste
or unpleasant odor. Excipients help in Masking taste, improving
appearance and Enhancing patient compliance. [2]
• Enhancing Drug Dissolution and Bioavailability :- Some excipients
improve drug solubility and dissolution by Improving wettability, Increase
in surface area and Enhancing the absorption. [2]
• Reducing Friction During Processing :- Lubricants, glidants, and anti-
adherents reduce friction between Powder and machine parts, Tablet and
die wall. They also prevent sticking and ensure smooth production. [2]
• Modified and Controlled Drug Release :-Modified and controlled release
excipients are special pharmaceutical substances used to alter the rate,
time, and site of drug release from tablets and capsules. They help in
maintaining constant drug levels in the body, reducing dosing frequency,
and improving patient compliance. [2]
CHARACTERISTICS OF IDEAL
EXCIPIENTS:-
 Non Toxic:- They must be nontoxic and acceptable to the regulatory agencies in
all countries where the product is to be marketed.[2]
 Easily Available:-They must be commercially available in an acceptable grade in
all countries where the product is to be manufactured.[2]
 Economical:-Their cost must be acceptably low.[2]
 Compatible:- They must not be contraindicated by themselves (e.g. sucrose) or
because of a component (e.g. sodium) in any segment of the population.[2]
 Inert:- They must be physiologically inert.[2]
• Stable:- They must be physically and chemically stable by themselves and
in combination with the drug(s) and other tablet and capsule components.[2]
• Free from microbes:-They must be free of any unacceptable microbiologic
“load.” [2]
• Colour Compatible:- They must be color-compatible (not produce any off-
color appearance). [2]
• Regulatory Acceptability :-Must be approved by regulatory authorities
(FDA, WHO, ICH, IP, BP, USP) and Should comply with pharmacopeial
standards. [2]
• Ease of Processing (Manufacturing Suitability) :- It Should have good
flowability and compressibility. It Must be suitable for large-scale
production and should be compatible with manufacturing methods. [2]
• Consistency and Reproducibility :- It Should show uniform performance
in every batch and must ensure uniform drug distribution.[2]
TABLE NO. [1]
EXCIPIENTS USE IN TABLET

TABLE NO. [2]

1) DILUENT (FILLER)
 In order to form tablets of a size suitable for handling, a lower limit in terms of
powder volume and weight is required.[1]
 Tablets normally weigh at least 50 mg.[1]
 Therefore a low dose of a potent drug requires the incorporation of a substance
into the formulation to increase the bulk volume of the powder and hence the size
of the tablet. [1]
 This excipient, known as the filler or the diluent.[1]
 Example :- Lactose, Sucrose, Glucose, Mannitol, Dicalcium Phosphate
dehydrate, Cellulose, Calcium carbonate.[1]
(A) LACTOSE :-
• Lactose is the most common filler in tablets.[3]
• It possesses a series of good filler properties, e.g. dis-solves readily in
water, has a pleasant taste, is non-hygroscopic, is fairly nonreactive and
has good Compactability.[3]
• It exists in both crystalline and amorphous forms.[3]

(B) CELLULOSE :-
• Celluloses, also known as cellulosics, are powdered derivatives of high-
grade edible celluloses and are widely used diluents in tablets and
capsules.[3]
• They are best suited to produce matrix systems for tablets and capsules
because of their aqueous swelling property wherein drug release is
controlled by its diffusion through the hydrogel layers formed.[3]
• Examples:- Hydroxyl propyl cellulose, HPMC, ethyl cellulose.[3]
2) DISINTEGRANTS:-
 A disintegrant is included in the formulation to ensure that the tablet, when in
contact with a liquid, breaks up into small fragments, which promotes rapid drug
dissolution.[1]
 The disintegration process for a tablet occurs in two steps.[1]
 First, the liquid wets the solid and penetrates the pores of the tablet. Thereafter,
the tablet breaks up into smaller fragments.[1]
 The actual fragmentation of the tablet can also occur in steps, i.e. the tablet
disintegrates into drug–excipient aggregates that subsequently deaggregate into
smaller aggregates and discrete particles. Deaggregation into drug particles will
set up conditions for the fastest possible dissolution of the drug.[1]
 Examples :- Starch, Sodium starch glycolate, Croscarmellose, sodium
Crospovidone.[1]
3) BINDERS:-
 A binder (adhesive) is added to a drug–filler mixture to ensure that granules and
tablets can be formed with the required mechanical strength. Binders can be added
to a powder in different ways:[1]
a) As a dry powder which is mixed with the other ingredients before wet
agglomeration. [1]
b) As a solution which is used as an agglomeration liquid during wet agglomeration .[1]
c) As a dry powder which is mixed with the other ingredients before compaction.[1]
 Starch, sucrose and gelatin are common traditional solution binders.[1]
 Polymers such as polyvinylpyrrolidone and cellulose derivatives (in particular
hydroxypropyl methylcellulose), are more commonly used binders today. [1]
4) GLIDANT :-
 The role of the glidant is to improve the flowability of the powder. Glidants are
used in formulations for direct compaction but are often also added to granules
before tableting to ensure that sufficient flowability of the tablet mass is achieved
for high production speeds.[2]
 Traditionally, talc has been used as a glidant in tablet formulations, in
concentrations of approximately 1% to 2% by weight.[2]
 Today, the most commonly used glidant is probably colloidal silica, added in very
low proportions (approximately 0.2% by weight). Because the silica particles are
very small, they adhere to the particle surfaces of the other ingredients (i.e. an
ordered or structured mixture is formed) and improve flow by reducing
interparticulate friction.[2]
5) LUBRICANTS :-
 The function of the lubricant is to ensure that tablet formation and ejection can
occur with low friction between the solid and the die wall. High friction during
tableting can cause a series of problems, including inadequate tablet quality and
may even stop production. Lubricants are thus included in almost all tablet
formulations.[2]
 Magnesium stearate has become the most widely used lubricant owing to its
superior lubrication properties. The stearic acid salts are normally used at low
concentrations (< 1% by weight) [2]
 The commonly observed retardation of disintegration and dissolution of tablets is
related to the hydrophobic character of the most commonly used lubricants. In
order to avoid these negative effects, more hydrophilic substances have been
suggested as alternatives to the hydrophobic lubricants.[2]
 Surface-active agents and polyethylene glycol are examples.[2]
6) FLAVOURS :-
 Flavouring agents are incorporated into a formulation to give the tablet a more
pleasant taste or to mask an unpleasant one.[1]
 Flavouring agents are often thermolabile and so cannot be added before an
operation involving heat.[1]
 They are often mixed with the granules as an alcohol solution.. [1]
 The examples of flavoring agents used in tablets include bitter flavors (anise, mint
or choclate), sour flavors (berries, orange, lemon), sweet flavors (fruits, sugars)
and salty flavor (butterscotch, vanilla, peach).[1]
7) COLOURANTS:-
 Colors are added in association with the flavors to complement their effect and
also to increase product elegance.[1]
 They are used to mask poor color of the drug and other additives, enhance appeal
and for the product identity.[1]
 Natural colors are obtained from minerals such as titanium dioxide, carbon, iron
salts as ferric oxides; animals such as carmine, various tyrian shades, phoenician
purple, imperial purple, or imperial dye and plants such as chlorophyll, indigo and
catechu.[1]
 Artificial colors require regulatory approval and may be Incompatible with the
drug thus, natural colors are preferably used.[1]
TABLE NO. [3]
EXCIPIENTS USE IN CAPSULES
 Most excipients used in tablets and capsules are similar, but their type and
quantity differ due to differences in manufacturing process.[3]
 Although many excipients are common, their use and importance differ.[3]
 Such as tablets need binders (PVP, starch paste) for strength while Capsules do
not need binders, because no compression occurs.[3]
 Tablet is a hard compact so it must break while Capsule shell dissolves easily,
hence Capsules often do not need disintegrants [3]
 In addition to these soft gelatin capsules also require Plasticizers, Fill materials,
Preservatives and Antioxidants.[3]
CAPSULE SHELL COMPOSITION

 Gelatin
 • Heterogeneous product derived by Irreversible hydrolytic extraction of animal's colkae
(obtained from animal skin and bone) Sources of gelatins → Animal bones, hide portions
and frozen pork skin.
Types of Gelatins

TABLE NO. [4]

Preparation of Gelatin

TABLE NO. [5]

 COMPONENTS OF HARD GELATIN CAPSULE SHELL
 1. Capsule shell :- Made up of gelatin with other excipients
Likedyes, Opaquant, plasticizers and preservatives Gelatin or its substituent
 2. Gelatin or its substituent :-It is heterogeneous product derived by hydrolytic extraction of
animal's collage
e.g.-Type A gelatin and Type B gelatin
 3. Colorants :-Water soluble dyes: Azo dyes (having an -N-N- linkage) and non-azo (e.g. Erythrosine,
indigo carmine, quinoline yellow)
• Insoluble pigments: • e.g.- Iron oxides- black, red and yellow.(0.1-5%)
 4. Opaquing agent :-Used to make the capsule opaque. e.g-Titanium dioxide (TiO2) (.0.5- 2%)
 5. Plasticizers :- Used to increase the elasticity of capsule shell • e.g.- Sorbitol, Glycerin, PEG(10-30%)
6. Preservatives :- Applied to prevent microbial contamination •(Methyl paraben and Propyl paraben
(4:1)). (0.1- 0.3%)
 7. Wetting agent :- 0.15% w/w of Sodium lauryl sulphate, to ensure that the lubricated metal moulds
are uniformly
1) PLASTICIZERS
 Plasticizers are substances added to polymeric materials to increase their
flexibility, softness, and elasticity.[3]
 In soft gelatin capsules, plasticizers are mainly used to prevent brittleness and
cracking.[3]
 Plasticizers reduce intermolecular forces between polymer chains, thereby
increasing their mobility and making the material more flexible.[3]
 There are 2 types of Plasticizers:-
 A) Internal plasticizers:- They are chemically bound to polymer and become part
of polymer structure. Example:- Modified cellulose derivatives[3]
 B) External Plasticizers:- It is physically mixed with polymer and not chemically
bound. Example:- Glycerin, Sorbitol, Propylene glycol.[3]
2) FILL MATERIALS (VEHICLES) :-
 Fill material is the substance used to carry, dissolve, or suspend the active
pharmaceutical ingredient (API) inside a capsule.[1]
 It forms the internal content of the capsule and plays a crucial role in drug
stability, bioavailability, and therapeutic effectiveness.[1]
 In simple words, fill material is the vehicle in which the drug is dispersed or
dissolved [1]
 They act as an Solvent for drug, Suspending Medium, Stability Enhancer.[1]
 Types of Fill Materials:-
 (A) Oily Vehicles:- Soybean oil, Castor oil, Cottonseed oil.[1]
 (B) Water Miscible:- PEG 400, PEG 600, Propylene glycol.[1]
 (C) Self Emulsifying Vehicles:- They are modern fill materials and contain oil +
surfactants+ co solvents.[1]
3) PRESERVATIVES
 Preservatives in capsules are added mainly to prevent microbial growth in the
gelatin shell and fill material.[1]
 Capsules contain moisture, plasticizers, and gelatin, which provide a favorable
environment for microorganisms. Therefore, preservatives are essential, especially
in soft gelatin capsules.[1]
 Preservatives maintains physical integrity of shell and increases shelf life of
capsule ensuring overall patient safety.[1]
 The examples of antimicrobial preservatives are benzyl alcohol, benzalkonium
chloride, methyl paraben, sodium sulfite.[1]
 Examples of antioxidant preservatives are Vitamin C, Vitamin E, BHA, BHT.[1]
MODERN TRENDS IN EXCIPIENTS.
1) Co-Processed Excipients :- Co-processed excipients are combinations of two
or more excipients processed together to improve their functional properties without
chemical modification.
 It Improved flowability, better compressibility and reduced segregation.
 Examples: Microcrystalline cellulose + Lactose (e.g., Cellactose®)MCC + Colloidal
silica (Prosolv®).
2) Multifunctional Excipients :- Single excipients performing multiple
functions in formulation.
 It Reduce number of ingredients and Simplify the formulation.
 Examples:- Crospovidone (binder + disintegrant), HPMC (binder + film former +
release modifier)
3) Novel Natural Excipients :- They are Derived from plants, algae, and
microorganisms.
 Examples:- Guar gum, Xanthan gum, Chitosan, Alginate.
 They are biodegradable, biocompatible and low toxicity.
4) Smart and Stimuli-Responsive Excipients :- They are the Excipients
that respond to environmental conditions.
 They are useful in target drug delivery.
 They can be PH – sensitive, Temperature sensitive , Enzyme- responsive.
 Example:- Eudragit S.
5) Nano-Excipients and Nanocarriers :- Excipients used in nano-sized
drug delivery systems.
 They enhance permeability and improve stability.
 Example:- Lipids, Dendrimers.
 Alternatives to Hard Gelatin Capsules
 - HPMC Capsules → Plant-derived, vegetarian option
 - Starch Capsules → Made from potato starch (12–14% moisture)
 - Crosslinked Dextran Capsules → Colon-specific drug delivery
REFERENCES
1) Pharmaceutics- The science of dosage form design by M.E. Aulton, Churchill
livingstone, fifth edition,
2) Theory and Practice of Industrial Pharmacy by Liberman & Lachman, fourth
edition.
3) Modern pharmaceutics by Gilbert S. Banker and Christopher T. Rhodes, Mercel
and Dekker Series, fourth edition.