Integrated Physical Pharmacy and

Pharmaceutics I

Introduction to dosage forms

by
Dr. Getahun Paulos (PhD)

Getahun P 1
 Introduction

• Pharmaceutics is concerned with the scientific

and technological aspects of the design,
development and manufacture of dosage forms

– Pharmaceutics converts a drug substance into a

dosage form (drug delivery systems)

Getahun P 2
 Introduction…
Pharmaceutics is the most diverse of all
subject areas in Pharmaceutical science  Assessment of compatibility
and encompasses
 Stability studies
1. Understanding of the basic
 Biopharmaceutical and
physicochemical properties of the drug
pharmacokinetic studies (in vitro, ex
and additives
vivo and in vivo)
2. The design and formulation of
 process development and scale up
medicines (dosage form design)

 Selecting route of administration and 3. The manufacturing of these

right dosage form medicines on both small scale

 Selection of excipients (type and (compounding) and a large scale

(pharmaceutical technology )
amount)
Getahun P 3
 Dosage forms
Dosage form

 a preparation devised to make possible the

administration of medications in a measured or

prescribed amount

 They are drug delivery systems. i.e. a means of

administering drugs to the sites of action within the body

in a safe, efficient, reproducible and convenient manner

Getahun P 4
• There are three major considerations in the design of dosage forms.

1. The physicochemical properties of the drug itself. These include

 particle size and surface area, solubility, dissolution, partition

coefficient, crystal properties, stability, organoleptic properties and

others
2. Biopharmaceutical considerations
 how route of administration and type of dosage form affects rate
and extent of absorption

Getahun P 5
3. Therapeutic considerations of the disease state, which in turn decide
 the most suitable type of dosage form, possible routes of administration

 the most suitable duration of action and dose frequency for the drug in
question

The principal objective of dosage forms design is to

 achieve a reproducible therapeutic response to a drug included in a
formulation which is capable of large scale manufacturing with
reproducible product quality

Getahun P 6
Reasons for converting drugs to dosage form (the need for
dosage forms)

1. To provide the mechanism for the safe and convenient

delivery of accuracy of dose

2. To mask bad odor and taste of drugs, e.g. coated tablets,

flavored syrup

3. To protect the drug from external environment

4. To protect the drug from internal environment

Getahun P 7
5. To provide liquid preparations of substances that are either

insoluble or unstable in the desired vehicle

6. If they are unstable and pH dependent, it is overcome by

buffering or using cosolvents.

7. To extend drug action

8. For topical administration, to insert drugs in body cavities for

local and systemic action.

9. To prepare injectable preparations

10. To prepare inhalation products

Getahun P 8
Types of dosage forms
• There are different types of dosage forms into which a drug
substance can be incorporated for the convenient and
efficacious treatment of a disease

Factors governing to have different types of dosage forms

 the nature of the drug
 the disease conditions

 biopharmaceutical considerations
Getahun P 9
Classification of dosage forms
I. Based on the physical state of the dosage form
 solid dosage forms: powders, granules, tablets, capsules
and suppositories
 liquid dosage forms: solutions, suspensions and emulsions
 semisolid dosage forms: ointments, creams, pastes, gels
 others: aerosols, implants

Getahun P 10
II. Based on routes of administration
Route
Dosage forms
Oral Solutions, suspensions, emulsions, gels, powders, granules, capsules,
tablets
Rectal Suppositories, ointments, creams, powders, solutions
Vaginal pessaries, tablets, capsules, solutions, creams, sprays, ointments, foams
Topical Ointments, creams, pastes, gels, solutions , aerosols
Parenteral Injections (solutions, suspension, emulsion), implants, irrigations and
dialysis solutions
Respiratory Aerosols (solution, suspension, emulsion, powder), inhalations, sprays,
gases
Nasal Solutions, inhalations
Eye Solutions, ointments, creams
Ear Solutions, suspensions, ointments, creams

Getahun P 11
Routes of drug administration

• It is one of the factors that should be considered during

dosage form design

• The most common routes of drug administration are

 Oral route (peros)

 The Buccal routes (oral cavity)

 The rectal route -The vaginal route

 Parentral route -Topical route

 Inhalation/respiratory/ route -The nasal route

Getahun P 12
1. Oral route (peros)

• Most frequently used

• Simplest, most convenient and safest route of administration

• Usually for systemic use but some times for local effect in the GIT

Disadvantages

• Slow onset of action

• Irregular absorption(inter-and intra-individual variability)

 Interaction with foodstuffs

 variation in gastric emptying

 disease conditions

 personal variations
Getahun P 13
• Destruction of some drugs by enzymes and other secretions of GIT

• First pass/presystemic metabolism (by enzymes in the GIT/liver)

• Unsuitable for unconscious or vomiting patients and for immediate pre- or

post operative use and incases of malabsorption states

2. The Buccal routes

 Administration of the drug into the oral cavity

 Can be used for both systemic and local action

• Two sites for absorption of drugs from the buccal cavity:

i. Sublingual absorption

 The area under the tongue

 Fast onset of action but the duration is usually

Getahun P short 14
ii. Buccal absorption

• The area between the upper lip and the gum

• Quick onset of action and can also give a longer duration of action

Advantages

• Relatively quick onset of action

• Drugs are absorbed systemically, there by avoiding the ‘first pass’ effect

• Drugs can be administered for unconscious patients

 Because the tablet is not swallowed

• The drugs for this route are usually formulated as tablets, sprays and gels

• The patient should be made aware of the difference between the two sites and

should be given full instruction on how to administer the drugs to ensure

maximum benefit Getahun P 15

3. The rectal route

• Administration of a drug into the rectum where the drug is released to give
local or systemic effect

Advantages

• Can be used when the oral route is unsuitable (incases of)

 Severe vomiting, Unconscious patients

 Uncooperative patients such as children, elderly or mentally disturbed and

patients with dysphagia

• Useful when the drug causes GIT irritation

• Can be used for local action (eg. Treatment of hemorrhoids)

• Can be used for drugs which are inactivated by GIT enzymes and secretions

• avoids presystemic metabolism (partially

Getahun P 16
Disadvantages

• Absorption is irregular and unpredictable, giving rise to

variable effect.

• Slow absorption (low fluid volume and low surface area)

• Less convenient than oral route

• Low patient acceptability

• Large dose is required (50% more than oral route)

Getahun P 17
4. The vaginal route

• Most often for local effect

• However, drugs absorbed form this route are not subjected to the first pass
effect

5. Parenteral route

• Drugs are injected via a hollow tube into the body at various sites and
varying depths.

• The preparations should be sterile

• The three main parental routes are:

i. intravenous (IV)

• Drugs are injected directly into the systemic circulations (veins).

• Produces the fastest onset of action

Getahun P 18
ii. Intramuscular route
– Drugs are injected into muscle layers

– Produce a fairly fast action when the drug is formulated as aqueous

solution

– A slower and more prolonged action will be obtained when the drug is

formulated in oily vehicle or as suspension

iii. Subcutaneous route

Drugs are injected to the subcutaneous layer of the skin

Easier and less painful

Other less frequently used parenteral routes include intracardiac,

intraspinal, interathecal, intrarterial,

Getahun P etc 19
Advantages
• Rapid onset of action (rapid absorption, directly into systemic
circulation)
• Prolonged effect can be obtained

• Useful in emergency situations

• Can be used for vomiting, unconscious and uncooperative

patients
• Used for GIT irritant drugs

• For drugs which are destroyed, inactivated, or poorly absorbed

form GIT
Getahun P 20
• Disadvantages
Inconvenient and less patient acceptance

Expensive, Tissue damage

Painful (there is trial of needle free injections)

Reversal of toxicities is difficult

6. Topical route
– Drugs are applied on the skin

Common dosage forms: powders, liquids, semisolids

– Reasons for application

for local effect (disease treatment, cosmetic purpose, protection)

For systemic effect (Very rare) Getahun P 21

• Although absorption from this site is poor and erratic, a constant blood

concentration can be obtained over a prolonged period of time (1-7 days).

• The application of drugs to other topical sites, such as eye and ear are also

included under this route.

Ophthalmic preparations should be sterile

7. The nasal route

• Has been traditionally used for producing local effects using solutions as

drops or sprays.

• More recently, it has been used for systemic action because of its good

vascular supply which avoids first pass metabolism although it does have

local enzyme activity

Getahun P 22
8. Inhalation/respiratory/ route

• Administration of drugs through moth or nose into the lung

• Predominantly used for local administration to treat respiratory

conditions such as asthma.

• Drugs are delivered directly to the site of action in low dose with
a consequent reduction in side effects.

• But there could be systemic toxicities because of high absorption

from lungs (high surface area of alveoli, high blood flow).

• Because of the high blood flow and large surface area, drug
absorption form this route is extremely rapid
Getahun P 23
Pharmaceutical excipients

24
1. Definition and goals

What are pharmaceutical excipients?

– The word “excipient” is derived from Latin word “excipere”,
meaning ‘ to except‘-'other than‘

• Pharmaceutical excipients
• Any component of a drug product other than an active ingredient added
intentionally to the medicinal formulation

• Conventionally/ideally, excipients should be inert

• Modern excipients however modulate
– solubility, bioavailability, drug delivery to the site of action, etc;

25
 Definition and goals…
Roles of conventional and Novel DD excipients
Therapeutics Compliance
• Effectiveness
• Pharmaceutical elegance
• Safety
– Appearance
• Reliability – Organoleptic properties
• Stability
– Physical
– Chemical • Convenience
– Microbiological – Ease of use
• Control release and – Dosing frequency
• Drug targeting – Consumer acceptance

26
 1. Solvents (vehicle)
• Medium in which active and other ingredients are
dispersed

• Choice of the vehicle depends on:

The intended use of the preparation
Physicochemical properties of the drug
Compatibility, Stability, Cost , etc

27
a. Water as a vehicle
• Vehicle of choice for most pharmaceutical ingredients
– Widely available,
– Relatively inexpensive
– Palatable (free of disagreable taste and smell)
– Non-toxic for internal use,
– Non-irritant for external use

Limitations
• Non-selective
• Solubility limit
• Hydrolytic degradation of ingredients
• Microbial contamination/growth

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 i. Potable water
• Drinking water, freshly drawn from the mains supply.

• Contains the highest level of impurities

– Dissolved inorganic ions
– Dissolved and undissolved organic matter

– Dissolved gases (O2, CO2)

 oxidation, PH change, incompatibility

– Microbially contaminated
• Not contain more than 0.1% total solids/residue/ (USP)

29
 ii. Purified Water
• Prepared from potable water by distillation, reverse
osmosis or demineralization (ion-exchange resins)
• Free of inorganic salts, organic matter and dissolved gases
• Could contain microorganisms.
• Contains not more than 0.001% total solids/residues/. i.e
1mg /100 ml. (0.001g/100ml)
• formulation of pharmaceutical dosage forms, except
sterile products
30
iii. water for injection (WFI)
• Sterilized purified water
• should be used within 24 hrs following its collection

– stored in sterile, pyrogen free, tight containers

• Contain not more than 0.001% of total solids
• Uses
– formulation of sterile products
– cleaning of equipments and containers of sterile products

31
 iv. Sterile water for injection

• WFI packed in single-dose containers of not more than 1lit

• Sterile and pyrogen free

• Don’t contain antimicrobial agent
• Used as a solvent or diluent for already sterilized and packed
injectabe medications

32
b. Non-aqueous vehicles
• Water couldn’t be used as a vehicle in some cases

• Solubility problem
• Stability problem (hydrolysis)
• Sustained release product of a water soluble drug (oily
injections)
• In such circumstances non-aqueous vehicles are used
• Alcohols

• Fixed oils
• Low M.Wt PEGs
33
 i. Ethanol
• Alcohol USP contains between 94.9 and 96.0% v/v ethyl
alcohol (ethanol)
• Widely used for external solutions; rarely used internally.
– commonly used as a co-solvent (e.g. hydroalcoholic solvents)

– Antimicrobial effect (>15%)

• Industrially methylated sprit (IMS)- used for external use.

• It is also useful for the extraction of crude drugs, being more

selective than water

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ii. Glycerol (Glycerin)

• Colourless, odourless, sweet viscous liquid

• It has similar co-solvency properties to ethanol.
• Used as a vehicle in some preparations.

• It is used as stabilizer and sweetener in internal

preparations.

• In concentration above 20%v/v it acts as preservative

35
 iii. Propylene glycol

• an odourless, colourless, viscous liquid contain 2

hydroxyl groups per molecule

• miscible with water, acetone, or chloroform in all

proportions. But not with oils

• As cosolvent with water for internal use

• Can be used alone for external use

• Is less viscous but better solvent than glycerin

36
 iv. Polyethylene glycol
• PEG is a polymer composed of repeating units of the
monomer ethylene oxide

– HO-CH2-(CH2-O-CH2-)n-CH2-OH

• available in a range of viscosity grades

• PEG 200, PEG 400 are preferred as
– co-solvents with alcohol or water

– formulation of water-miscible ointment bases.

37
 v. Fixed oils
• Vegetable origin, edible, digested in the gut
• Fatty acid esters of glycerol
• Almond oil, arachis oil, Corn oil, olive oil, caster oil, cottonseed oil,
soya been oil, etc.
• Used as a vehicle for lipophilic drugs: eg vitamins (A, D)

• Depot preparations of polar drugs (emulsion, suspension)

• Oily taste, hence unpleasant for oral use
• Encapsulated in soft gelatin capsules

38
 vi. Miscellaneous solvents
• Isopropyl myristate and isopropyl palmitate

– used as solvents for external use, particularly in cosmetics

• Dimethylformamide and dimethylacetamide

– used as solvents in veterinary formulation

• Xylene is present in some ear drops for human use to dissolve

ear wax

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2. Preservatives
– Prevent microbial spoilage of the product

– minimize the risk of the consumer acquiring infection from DFs

• Ideally, preservatives should exhibit the following properties:

– possess a broad spectrum of antimicrobial activity

– chemically and physically stable over the shelf-life of product

– low toxicity & employed at low conc. than antiseptics

01/18/2022 EXCIPIENTS 40
Preservatives for oral solution
Preservatives for
• Benzoic acid and its salts (0.1–0.3%), topical solutions
• Sorbic acid and its salts (0.05–0.2%)
– Chlorcresol,
• Alkyl esters of parahydroxybenzoic
– Chlorbutanol,
acid (0.001-0.2%)
– Parabens
– They are commonly called parabens

01/18/2022 EXCIPIENTS 41
 3. Antioxidants
Antioxidants commonly used for
Aqueous systems Oil systems
• Antioxidants are included
Na Sulfite* Ascorbyl palmitate
in pharmaceutical solutions Na metabisulfite* Hydroquinone
Na bisulfite * Propyl gallate
to enhance the stability by Ascorbic acid * BHA
Isoascorbic acid* BHT
preventing chemical Na thiosulfate* Tocophenols
Thioglycerol Lecithin
degradation by oxidation Thiosorbitol
Thiourea
Thioglycolic acid
Cysteire HCl

01/18/2022 EXCIPIENTS 42
 4. Buffering Agents
• Enable the solution to resist any change in pH
• pH affects solubility, stability and safety

• Buffers usually contain mixtures of a weak acid & one of its salts
(or a weak base and one of its salts)
– Acetates (acetic acid & sodium acetate): 1–2%
– Citrates (citric acid & sodium citrate): 1–5%
– Phosphates (Na phosphate & di Na phosphate): 0.8–2%.

• Typically pH control is performed for pH dependent

– To solubility of the therapeutic agent
– to enhance the stability of products

01/18/2022 EXCIPIENTS 43
 5. Viscosity enhancing agents

• Used • Non-ionic (neutral) polymers

– in suspensions to deter – Cellulose derivatives, e.g.: MC,
sedimentation, HEC, HPC
– in ophthalmic solutions to – Polyvinylpyrrolidone

enhance contact time,

– to thicken topical creams, • Ionic polymers
– etc – sodium carboxymethylcellulose

(anionic)
– Sodium alginate (anionic).

01/18/2022 EXCIPIENTS 44
 6. Isotonicity modifiers
• Required for

– Solutions applied to mucus membranes,

– injections and

– ophthalmic solutions

• Used to avoid irritation, pain, cell lysis

• E.g. NaCl and dextrose

01/18/2022 EXCIPIENTS 45
7. Surface-active agents
• Types of surface-active agents
– (1) anionic; (2) cationic; (3) nonionic; and (4) amphoteric.
a. Anionic surfactants
– Na /K salts of fatty acids : E.g. Na oleate, Na stearate

– Amine salts of fatty acids: E.g. triethanolamine stearate.

– Alkyl sulphates E.g. Na lauryl sulphate

b. Cationic surfactants
– cetrimide, Benzalkonium chloride and
Benzalkonium bromide.
01/18/2022 EXCIPIENTS 46
 c. Non-ionic surfactants

• Sorbitan esters (e.g. Span series)

– Fatty acid + hydroxyl groups of sorbitan

• Polyoxyethylene fatty acid derivatives of the sorbitan esters

(e.g. Tween series)

• Polyoxyethylene alkyl ethers (macrogols)

– PEG + fatty alcohols (lauryl, oleyl, cetyl, stearyl).

01/18/2022 EXCIPIENTS 47
 d. Amphoteric surfactants

• These are compounds that possess both positively and

negatively charged groups
– (cationic at low pH values and anionic at high pH values).

• The most commonly used amphoteric surface-active agent is

lecithin
– Lecithin is used in emulsions (for IV and IM adm. ) and creams, in
which it acts as an o/w emulsifying agent.

01/18/2022 EXCIPIENTS 48
 8. Sweetening agents
• increase the palatability of the therapeutic agent.
• The main sweetening agents employed in oral preparations are
– Sucrose, glucose
– Polyhydric alcohols such as sorbitol, mannitol and, glycerol
– Artificial sweeteners-saccharin sodium and aspartame.

EXCIPIENTS 49
9. Colouring Agents
• The Food Drug and Cosmetic Act of 1938 created
three categories of Dyes
– FD&C colors: These are colorants that are certifiable for
use in foods, drugs, and cosmetics.
– D&C colors: These are safe for use in drugs and cosmetics
when in contact with mucous membranes or when
ingested.
– External D&C colors: These colorants, due to their oral
toxicity, are not certifiable for use in products intended for
ingestion

50
Classification
A. Organic dyes and their lakes
B. Inorganic or mineral colors
C. Natural colors or vegetable and animal colors

Organic dyes and their lakes

• Dyes are synthetic, chemical compounds (soluble)
– E.g: Erythrosine, Patent Blue V , sunset yellow, Tarterazine lemon
yellow
• Lakes
– Lakes are “calcium and Aluminum salts of FD&C water soluble dyes.

51
• Inorganic or mineral colors
– e,g. Titanium dioxide, red & yellow ferric oxide
• Natural colors
– For example, β‐carotene , chlorophyllin

52
Widely used colorants in pharmaceuticals
• FD&C Blue No. 1 – Brilliant Blue, (blue shade)
• FD&C Blue No. 2 – Indigotine, (indigo shade)
• FD&C Red No. 3 – Erythrosine, (pink shade)
• FD&C Red No. 4 – Allura Red, (red shade)
• FD&C Yellow No. 5 – Tartrazine, (yellow shade)
• FD&C Yellow No. 6 – Sunset Yellow, (orange
shade)
 10. Ointment Bases

• Substance or part of an ointment preparation

which serves as carrier or vehicle for the
medicament

• Classification of ointment bases:

1. Oleaginous bases 2. Absorption bases
3. Water-miscible bases 3. Water soluble bases
Oleaginous bases
• Paraffins (hard paraffin, soft
paraffin, liquid paraffin)

Absorption bases
• Wool fat (anhydrous lanolin),
hydrous wool fat (lanolin),
wool alcohol, bees wax
Water-miscible bases
 Emulsifying ointment B.P. - contains anionic emulsifier
 Cetrimide emulsifying ointment B.P. - contains cationic
emulsifier
 Cetomacrogol emulsifying ointment B.P. - contains non-ionic

Water soluble bases

• Macrogols (Polyethylene glycols)

56
Gelling agents
 Viscosity enhancers
 Examples: tragacanth, sodium alginate, pectin, starch,
cellulose derivatives
11. Suppository Bases

Suppository bases fall into two classes -

1. Fatty bases or oleaginous bases

i. Theobroma oil

ii. Hydrogenated oil

2. Water-soluble or water miscible bases

iii. Glycero-gelatine
iv. Polyethylene glycol

Getahun P 58
 1. Fatty bases
i. Theobroma oil (Cocoa butter)
– Fat obtained from the roasted seed of
Theobroma cacao.
– At room temperature- yellowish-white
solid (chocolate-like odour)
– Cocoa butter melts between 30C to
36C, it is an ideal suppository base
– Cocoa butter exhibits marked
polymorphism

Getahun P 59
 Fatty bases…
Chemically,
– Predominantly triesters
• Primarily of oleopalmitostearin and oleodistearin
• Mixture of glyceryl esters of stearic, palmitic, oleic and other
fatty acids.
– The unsaturated (e.g. oleic acid) esters contributes to the low
m.pt of cocoa butter (30–360C

Getahun P 60
 Fatty bases…
ii. Synthetic fats
• As a substitute of theobroma oil

• They are hydrogenated oils

– hydrogenated edible oil, arachis oil, coconut oil, palm
kernel oil, stearic and oleic acids
• Mixtures of triglycerides of higher saturated fatty acids (C8-C18)
and di/monoglycerides

Getahun P 61
 Fatty bases…

Synthetic Emulsifying fatty bases

• Witepsol
– Triglycerides of saturated vegetable acids (C12 to C18) with
varying proportions of partial esters

• Massa Esterium
– Consisting of a mixture of di-, tri- and mono- glycerides of
saturated fatty acids with chain lengths of C11 to C17.
• Massuppol
– It consists of glyceryl esters mainly of lauric acid, to which a
small amount of glyceryl monostearate has been added

Getahun P 62
 2. Water soluble & water miscible bases
i. Glycero-Gelatin base
• Mixture of glycerol (70%w/w) & water made into a stiff jelly by adding
gelatin (14%w/w).
• In hot climates the gelatin content can be increased to 18% w/w.
• Urethral suppositories may be prepared from a glycerinated gelatin
base (60% gelatin, 20% glycerin and 20% medicated aqueous portion)
• The base being hydrophilic in nature,
– slowly dissolves in the aqueous secretions
– provide a slow continuous release of medicament

Getahun P 63
 Water soluble & water miscible bases…
ii. PEG/ Macrogol bases (Carbowaxes)
• Depending on their molecular weight they are available in
different physical forms.
• Macrogol 400
• Macrogol 1000
• Macrogol 1540
• Macrogol 4000
• Macrogol 6000
– These PEG can be blended together to produce suppository
bases with varying melting points, dissolution rates and
physical characteristics.

Getahun P 64
Pharmaceutical Excipients for solid dosage forms

• Diluents
• Granulating agents,
• Lubricant/Glidant/Anti-adherant,
• Coating excipients

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1. Diluents or fillers

 Diluents make the required bulk of the drug

substance
– For e.g. diazepam, clonidine hydrochloride
• The range of diluent may vary from 5-80%.

• Secondary reasons of using diluents

– To provide improved cohesion
– To allow direct compression manufacturing
– To enhance flow
– To adjust weight of tablet as per die capacity
 Diluents…
Fillers can be divided into following categories:
i) Organic materials –
 Carbohydrate and modified carbohydrates.

ii) Inorganic materials –

• Calcium phosphates and others.

iii) Co-processed Diluents.

 Diluents…
Organic diluents
i/ Carbohydrates
Sugar and Sugar alcohols
• Lactose: -
– α-lactose monohydrate,
– spray dried lactose and
– anhydrous lactose
• Sucrose
– It possesses good binding properties.
– It is slightly hygroscopic.
– It is inexpensive
 Diluents…
• Mannitol
– Mannitol a sugar alcohol is an optical isomer of
Sorbitol.
• Sorbitol
– Sorbitol is often combined with mannitol
formulations in order to reduce diluent cost.
– It is highly compressible diluent and is water soluble.
– It is hygroscopic in nature.
– It has good mouth feel and sweet cooling taste.
 Diluents…
Celluloses
• Powdered cellulose
– Consist of finely divided amorphous &crystalline α-cellulose
particles.
– Powdered cellulose may be used alone or together with other
fillers such as lactose, calcium phosphates,
• Microcrystalline cellulose
– the most widely used direct-compression tablet diluent.
– It exhibits binding properties.
– It also possesses disintegrant activity and thus promotes fast
tablet disintegration.
 II. Inorganic diluents
• Calcium phosphates
– The dihydrate and anhydrous form of dibasic calcium
phosphate and tribasic calcium phosphate.
– They are granular insoluble materials.
– They are widely used both as wet granulation and direct
compression diluents in tablet formulation.
– They are directly compressible
– Hard tablets are produced when calcium phosphates are
used as diluents.
– They exhibit good flow properties.
– They are non hygroscopic.
 III. Co-processed diluents
• combining two or more materials by an
appropriate process.
Co processed Exp. Trade name Added advantage
Lactose, 3.2% Kollidon 30, Ludipress Low degree of hygroscopicity, good
Kollidon CL flowability
Lactose, 25 % cellulose Cellactose Highly compressible, good mouthfeel
Sucrose, 3% Dextrin DiPac Directly compressible
MCC, silicon dioxide Prosolv Better flow, better hardness of tablet,
reduced friability.
MCC, guar gum Avicel CE-15 Less grittiness, creamier mouth-feel,
improved overall palatability
Calcium carbonate ForMaxx Controlled particle-size distribution
Sorbitol
MCC cellulose, lactose Microcelac Capable of formulating high dose, small
    tablets with poorly flowable active
95% β-lactose + Pharmatose High compressibility, low lubricant
5% Lactitol DCL40 sensitivity
85% - lactose MH + 15% StarLac Good flow
native corn starch  

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 Fillers and binding fillers suited for DC
solubility type Examples flowability compactability
water Saccharides lactose, milled - +
soluble lactose, DC grade + +
Dextrates + +
Glucose + -
Saccharose + +
Polyols Sorbitol + +
Mannitol + +
Xylitol + +
water Cellulose powdered cellulose fine - +
insoluble powdered cellulose coarse + -
MCC fine - ++
MCC DC + +
silicified MCC + ++
Inorganic salts DCP ++ +

74
 2.Binders or Granulating agents or
Adhesives
• Binders are added to tablet formulations to
add cohesiveness to powders, thus providing
the necessary bonding to form granules,
which under compaction form a cohesive
mass or a compact -tablet
 Types of Binders
NATURAL  SYNTHETIC/SEMISYNTHETIC 

Acacia Methyl  Cellulose

Tragacanth Ethyl  Cellulose
Gelatin Hydroxy  Propyl  Methyl  Cellulose

Starch  Paste Hydroxy  Propyl  Cellulose

Pregelatinized  Starch Sodium  Carboxy  Methyl  Cellulose

Alginic  Acid Polyvinyl Pyrrolidone (PVP)

Cellulose Polyethylene  Glycol (PEG)
 Sucrose and glucose Polyvinyl  Alcohols
Polymethacrylates
 Binders…

Starch Cellulose
(1,4-alpha-glycosidic linkages) (1,4-beta-glycosidic linkages)

Polyethylene glycol (PEG)

Gelatin

Binders add mechanical strength to the tablet or granules.

 Binders…

Starch (100 to 6000 glucose units)

Starch has 1,4-alpha linkages

Cellulose (1800 to 3000 glucose units)

Cellulose has 1,4-beta linkages
 Binders…
Characteristics of commonly used binder

Binder type Conc. Comments

Starch Paste 5-25%w/w - Freshly prepared starch paste is used as a binder.
Pregelatinized 5-10%w/w Physically modified starch
Starch (PGS) -It contains 5% free amylose, 15% free amylopectin
& 80% unmodified starch.

HPMC 2-5%w/w - Comparable to Methyl Cellulose.

- Used as a binder in either wet or dry granulation
processes.

Polyvinyl 0.5-5%w/w - Used in wet granulation process.

Pyrrolidone (PVP) -It is also added to powder blends in the dry form
 3. Disintegrants
• Disintegrants are used to induce breakup of tablet when it
comes in contact with aqueous fluid

• Mechanism of tablet disintegrants

– By capillary action
– By swelling
– Because of heat of wetting
– Due to disintegrating particle/particle repulsive forces
– Due to deformation
– Due to release of gases
– By enzymatic action
 Disintegrants…
Methods of addition of disintegrants
• Disintegrating agent can be added either prior
to granulation or
• Prior to compression (after granulation) or
• At the both processing steps.
 Disintegrants…
Types of disintegrants
– Starch,
– Pregelatinized starch
– Sodium Starch Glycolate
– NaCMC
– Microcrystaline Cellulose
– Alginic Acid
– Gums
– Crospovidone
 Super-disintegrants

SUPERDISINTEGRANTS EXAMPLE MECHANISM OF ACTION

Crosscarmellose® Cross-linked  Swells 4-8 folds in < 10 sec
cellulose
Crosspovidone Cross-linked PVP  Swells very little but act by
capillary action
Sodium starch glycolate Cross-linked starch  Swells 7-12 folds in <30 sec 
Satialgine® Cross-linked  Rapid swelling in aqueous
alginic acid medium
 4. Antifrictional Agents
• Lubricants
– are the agents that act by reducing friction
• Interpose an intermediate layer b/n the powder
constituents and the die wall during compression and
ejection.
• Ex. Magnesium stearate
 INSOLUBLE LUBRICANTS CONC. COMMENTS
Stearates(Magnesium Stearate,
Calcium Stearate, Sodium 0.25 -1 Reduce tablet strength; prolong
disintegration; widely used.
stearate)
Insoluble but not hydrophobic;
Talc 1 -2 moderately effective.
Waxes 1-5 -
Glyceryl
behapate(Compritol(r)888) 1-5 Both lubricant and binder;

Dispersion problem; inferior to

Liquid paraffin Up to 5 stearates

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WATER SOLUBLE LUBRICANTS CONC. (%W/W)

Boric acid 1
Sodium benzoate 5
Sodium oleate 5
Sodium acetate 5
Sodium Lauryl sulfate (SLS) 1-5
Magnesium lauryl sulfate (MLS) 1 - 2

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 Antifrictional…
• Antiadherents
• antiadherents are added, which prevent
sticking to punches and die walls.
• Talc, magnesium stearate and corn starch
 ANTIADHERENT Conc.(%W/W) COMMENT
Lubricant with excellent antiadherents
Talc 1-5
properties
Lubricant with excellent antiadherents
Cornstarch 3 - 10
properties
Does not give satisfactory results due to
Colloidal silica 0.1 - 0.5
small surface area. Cab-O-Sil(r) and Syloid(r)
Water soluble lubricant; excellent
DL-Leucine 3 - 10
antiadherents properties
Antiadherents with water soluble
Sodium lauryl sulfate <1
lubricant
Antiadherents with water insoluble
Stearates <1
lubricant

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Glidants
• Used to improve the flow properties of the material
which is to be fed into the die cavity and aid in
particle rearrangement within the die during the
early stages of compression.
– Starch
– Silaceous material like colloidal silica
 6. Miscellaneous Excipients
Wetting Agents
• Aid water uptake and thereby enhancing disintegration
and assisting in drug dissolution.
• like Sodium Lauryl Sulphate (SLS)
Adsorbents
• Agents that can retain large quantities of liquids
like Vitamin E
• anhydrous calcium phosphate, starch, magnesium
carbonate, bentonite, kaolin, magnesium silicate,
magnesium oxide and silicon dioxide.