Integrated Physical Pharmacy and Pharmaceutics I
(Phar 2091)
Unit 1
Introduction to dosage forms and routes of drug administration
Dr. Mohd Yasir
M. Pharm, Ph.D
Assistant Professor
Dept of Pharmacy, College of Health Sciences, Arsi University, Assela, Ethiopia
1
Drug ?
Active drug substance (active pharmaceutical ingredient - API)
Chemical compound with pharmacological action intended for used in
diagnosis, mitigation, treatment, cure or prevention of disease.
International non-proprietary names (INN, „generic“ names).
Direct clinical use of the active drug substances is rare: Why??
API handling and Accurate dosing can be difficult or impossible (e.g.,
potent drugs: low mg and µg doses)
API administration can be impractical/unfeasible because of size,
shape, smell/odour, taste and low activity.
Stability: Some API are chemically unstable in light, moisture, O2
API can be degraded at the site of administration (e.g., low pH in
stomach).
API may cause local irritations or injury when they are present at high
2
concentrations at the site of administration.
Dosage forms:
Definition: Drugs are rarely administered in their original pure
state. They are converted into suitable formulation which are called
dosage forms.
Every dosage form is a combination of the drug and other non-drug
components.
Dosage forms are the means by which drug molecules / APIs are
delivered to sites of action within the body/ topically to produce
optimum desired effects and minimum side/adverse effect.
Need of dosage forms: overcoming the difficulties of API
1. To provide for the safe and convenient delivery of accurate dosage
Examples: Tablets, Capsules, syrups
2. Protection of form atmospheric oxygen or moisture. Examples:
coated tablets, sealed ampoules/vials
3. Protection of a drug substance from gastric acid after oral
3
administration. Example: enteric coated tablets
4. To conceal the bitter taste, obnoxious odor of a drug substance.
Examples: Capsules, coated tablets, flavored syrups
5. To provide liquid preparations of substances that are either
insoluble or unstable in the desired vehicle. Example: suspension
6. To provide liquid dosage forms of substances soluble in desired
vehicle. Example: solution
7. Sustained release and controlled released medication.
8. Optimal drug action for topical administration sites. ointments,
creams, ophthalmic, ear and nasal preparations
9. Insertion of drugs into body cavities like Examples: rectal and
vaginal suppositories
10. To provide for the placement of drugs within body tissues.
Examples: Implants
11. To provide for the optimal drug action through inhalation
therapy. Examples: inhalants and inhalations.
4
Classification of Dosage form
Solid dosage
forms
Unit dosage
forms
Bulk
Liquid dosage
forms
Biphasic
Emulsion
Suspension
Tablets
Capsule
Powders
Pills
Internal
Fine powders &
granules
External
Dusting powders
Insufflations
Dentifrice
Snuffs
Monophasic
Internal
Syrups
Elixirs
Linctus
Drops
Gaseous
Semi solid dosage
e.g.
forms
Aerosols,
Inhalation
Internal (Non oral)
External
Liniments
Lotions
Gargles
Throat paints
Mouth washes
Sprays
Eye lotions
Eye drops
Nasal drops
External
Ointment
Creams
pastes
Jellies
Suppositories
Pessaries
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Solid dosage forms
One of the oldest dosage forms
Most of the solid dosage forms are available in Unit dose (exact
quantity of the drug administered at once). Eg. e.g. Tablets, Capsule,
pills, cachets etc.
When drugs are to be administered orally in dry state, then tablets,
capsules are most convenient dosage forms.
Some solids are supplied in bulk (Means quantity available in
large). Bulk powders can be supplied as Internal (Granules, Fine
powders) as well as External (Dusting Powders, Insufflations etc).
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1. Dusting Powders:
Applied externally to skin in a very fine state (passed through
sieve no 80) to avoid local irritation.
Prepared by mixing of more than one ingredients in which either
starch, kaolin or talc are used in their formulation. Generally talc or
kaolin are used because they are inert in nature.
Dusting powders are used for, astringent,
antiperspirant , antiseptic, absorbent etc.
May be two sub type:
I) Medical dusting powder: used to increase
superficial condition of skin.
These are not applied on wounds, burns etc
II) Surgical Dusting powders: used in body
cavities and on major wounds like as burns etc.
They should be sterilized before use.
They are mainly used for their antiseptic, absorbent action.
7
2. Insufflations
These are medicated dusting powders meant for introduction into
body cavities (nose, throat, ear, vagina etc) with the help of an
apparatus known as a insufflator that sprays the powders (in a state of
fine particles) on site of application.
3. Snuffs
These are finely divided solid dosage forms of medicaments which
are inhaled into nostrils.
They are mainly used for their antiseptic, bronchodilator and
decongestion action.
4. Cachets /Sachets
Consists of a dry powder enclosed in a shell. Usually unit dosage
form
Before administration, a cachet should be immersed in water for
few seconds and then placed on the tongue and swallowed
8
5. Dentrifices (Tooth preparations)
Dentrifices are preparations, used with the help of tooth brush
for cleansing the surfaces of the teeth.
They are available in the form of fine powders and pastes.
They contain
1. Some abrasive substance like calcium sulfate, magnesium
carbonate, sodium carbonate in fine powder.
2. Sweetening agent e.g. saccharin sodium
3. a suitable flavour e.g. peppermint oil, clove oil.
6. Granules
Granulation is the process in which primary powder particles are
made to adhere to form larger multiparticle or large particles
entities called granules exhibiting better flow properties during
tabletting
9
These powders are mixed with suitable excipient along with
granulating agent (starch past), prepare a coherent mass & passed
through the sieve to obtained desired size of granules and then dry.
E.g. Effervescent granules
Effervescent granules: are meant for internal use and quick action
They contained medicaments mixed with citric acid, tartaric acid &
sodium bi carbonates, sometime saccharin or sucrose may be added
for sweetening taste.
Before, administration desired quantity of granules are dissolved in
water, the acid & bicarbonate reacts with each other to produce
effervescence.
The quantity of acid is slightly more than is necessary to neutralise
the sodium bicarbonate because effervescent preparations are more
palatable if slightly acidic.
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CH2COOH
HO
C COOH
CH2COONa
. H2O
+ 3 NaHCO3
=
HO
CH2COOH
H
Tartaric acid
3CO2 + 4H2O
Ttrisodium citrate
H
H
HO C COOH
+
CH2COONa
Citric acid (monohydrate)
HO C COOH
C COONa
+
2 NaHCO3
=
HO C COONa
HO C COONa
+ 2CO2 + 2H2O
H
Disodium tartarate
Capsules
Capsules are solid unit dosage form in which one or more
medicaments are enclosed in a water soluble, biodegradable shell
made up of gelatin.
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Mainly for oral administration (intended to be swallowed whole) but
soft gelatine capsules may be intended for rectal or vaginal insertion
as suppositories.
Capsules are of two types: Hard gelatin capsules and Soft gelatin
Capsules
Hard gelatin capsules: also known as dry-filled capsules.
Hard gelatin capsules consists of two parts known as capsule body
(longer part, slightly narrow) and the capsule cap (the shorter part,
slightly broad).
The drug substance placed in the body and the caps are sided over it,
hence enclosing the drug substance.
Soft gelatin capsules are flexible in nature. They may be spherical,
ovoid cylindrical or tubes.
The small spherical capsules are also known as ‘pearls’. soft gelatin
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capsules are used to enclose solids, semisolids or liquids.
Tablets
 These are unit solid dosage forms of medicaments meant for oral
administration,
which are prepared by moulding or by
compression with or without Excipients.
 The tablets can be prepared by two methods namely as a
I) Dry granulation, II) Wet Granulation
Pills
 These are small, rounded
solid dosage forms containing
medicaments intended for oral use.
 The mass is rolled to uniform pill pipe, which cut into numbers of
uniform pills.
 Sometimes pills are coated with varnish, gold leaf, etc to improve
finish, unpleasant taste & stability.
 Now a days pills are outdated preparations as difficult to prepare
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pills of uniform size & weight
Lozenges
Lozenges are solid dosage form of medicaments which are meant
for slow dissolution in the mouth. Along with medicament they
contain a sweetening agent, flavoring agent and a strong binding
agent.
They may be prepared either by moulding or by compression.
Examples are compound bismuth lozenges, liquorice lozenges
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Liquid dosage forms
It may be defined as “A solution is a liquid-preparation that
contains one or more soluble chemical substances dissolved in a
specified solvent”
 Liquid dosage forms are intended for External, Internal or
parenteral use.
 The component of the solution which is present in a large quantity
is known as “SOLVENT” where as the component present in small
quantity is termed as “SOLUTE”
Advantage
 Immediately available for absorption.
 Administration convenient, particularly for infants, psychotic
patients as are easier to swallow than solids and are therefore
particularly acceptable for pediatric patient.
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Disadvantage
 Less stable in aqueous system. Incompatibility is faster in
solution than solid dosage form.
 Patients have no accurate measuring device.
 Accident breakage of container results in complete loss.
 Solution often provide suitable media for the growth of micro
organisms.
 The taste of a drug, which is often unpleasant, is always more
pronounced when in solution than in a solid form.
 Bulky than tablets or capsule, so difficult to carry transport.
They mainly classified in to two category namely as –
I) Monophasic Liquid dosage forms.
II) Biphasic liquid dosage forms.
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Monophasic liquid dosage forms
Monophasic liquid dosage forms are represent by true or
colloidal solution.
A solution is homogenous because the solute is an ionic or
molecular forms of subdivision.
In case of colloidal solutions, the solutes are present as
aggregates although they cannot be seen by necked eye or
ordinary microscope.
It is sub classified as –
I) Internal Use, II) External use
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Monophasic Liquid Dosage forms
Internal Use
 Syrup
 Elixirs
 Linctuses
 Drops
Draught
Single dose liquid is known as
Draught
External Use
Liniments Applied
 Lotions
to skin
 Gargles
 Mouth Wash For
 Throat paints body
cavities
 sprays
 Inhalations
 Nasal drops
 Eye drops
 Eye lotions
 Ear drops
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Monophasic liquid dosage forms for Internal Use
1. Syrup
 It is a concentrated or saturated solutions of sucrose in purified
water.
 The concentration of sucrose is 66.7% w/w (I.P)/64.74 % w/w or
85 % w/v (USP) & due to that it is a viscous preparations.
 The syrup which contains medical substance called as a medicated
syrup & those containing aromatic or flavored substance known
as a flavored syrup.
Importance of syrup
It retards oxidation because its partly hydrolyzed into reducing
sugar.
It prevents decomposition of many vegetable substance because its
have high osmotic pressure which prevent the growth of bacteria.
 They are palatable due sweet taste.
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2. Elixirs

It is clear, sweetened, aromatic, hydroalcholic preparations (10 20%) meant for oral use.

The medicated elixirs are generally contained potent drug like as
antibiotics, antihistamine or sedative , where as non – medicated elixirs
contained flavoured.

The composition of elixirs contained mainly as ethyl alcohol (active
ingredients),water, glycerin or propylene glycol, colouring agent,
flavouring agent & preservative.
3. Linctuses
These are viscous liquid preparations that’s are used for the treatment of
cough.
They contain medicaments which have demulcent (which soothes the
inflammed mucous membrane ), sedative, expectorant action.
They are taken in small doses without diluting with water to have
prolonged effect of medicines.
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Simple syrup is used as a vehicle for most of the linctuses.
4. Drops
These are liquid preparations meant for oral administration.
The oil soluble vitamins, such as vitamin A & D concentrates in
fish – liver oil are presented as drops for administration.
Since these preparations contain potent medicaments, the dose
must be measured accurately.
The following two methods are commonly used for this purpose.
Use of a dropper which is accurately graduated in fractions of a
milliliters.
Use of a pre – calibrated dropper.
Monophasic liquid dosage forms for External use
1. Liniments
Liniments are liquid or semi- liquid or semi- solid preparations
applied to the skin with friction & rubbing of the unbroken skin.
Are usually alcoholic and oily liquid preparations.
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Used generally for their rubefacient and counterirritant effects due
to presence of turpentine or methyl salicylate . Camphor is added to
promote the local action.
 Liniments should not be applied to skin that are bruised or
broken. They can be applied on lint and then placed on effected area
Lotions
Are the liquid preparations intended for external application
without friction or rubbing to the affected area
Usually applied with the help of some absorbent material such as
cotton wool or gauze.
It is generally used to provide cooling, soothing and protective &
antiseptic action.
Gargles
Gargles are aqueous solutions used for treating throat infection
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(pharynx and nasopharynx part)
Supplied in concentrated forms with directions of dilution with
warm water before use
They are used into intimate contact with the mucous membrane of
throat for few seconds, before they are thrown out of the mouth.
They are used to relieve soreness in mild throat infection.
Mouth wash/ mouth rinse
These are hydroalcoholic solutions with pleasant or acceptable
taste & odour
These are used to make clean & deodorise the buccal cavity or
used for oral hygiene and to treat infections of the mouth.
They mainly contain antibacterial agent, alcohol, glycerin,
sweetening agent, flavoring agent & colouring agent.
Dilution is not required
Throat paints
are viscous liquid preparations used for mouth and throat infections
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
Glycerin is commonly used as a base because being viscous it
adheres to mucous membrane for long period and it possess a
sweet taste.
Inhalations
These are liquid preparations containing volatile substance & are
used to relieve decongestion & inflammations of respiratory tract.
The volatile substance in inhalations would be volatile at room
temperature so that they should be placed on some adsorbent pad or
handkerchief.
In some cases inhalations will added to hot water (650c) then
vapors will inhaled.
Nasal drops
Drugs in solution may be instilled into the nose from a dropper or
from a plastic squeeze bottle.
The drug may have a local effect, e.g. antihistamine, decongestant.24
Alternatively the drug may be absorbed through the nasal mucosa
to exert a systemic effect.
The use of oily nasal drops should be avoided because of possible
damage to the cilia of the nasal mucosa & if it is used for long period
may reach the lungs & cause lipoid pneumonia.
To avoid that Nasal drops are prepared so that they are similar in
many respects to nasal secretions, so that normal ciliary action is
maintained thus aqueous nasal solutions usually are isotonic and
slightly buffered to maintain a pH of 5.5 to 6.5.
Eye drops/Ear drops
Sterile, aqueous/oily solutions intended for instillation in eye sac.
Single dose container should not contain anti-microbial
preservative.
 In case of multi dose container a dropper should be supplied with
it for administration.
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Extracts
Extracts are concentrated preparations containing the active principles of
vegetable or animal drugs
Tinctures
These are alcoholic preparations containing the active principles of
vegetable drugs.
They are weaker than extracts.
Spirits
Spirits are alcoholic or hydroalcoholic solutions of volatile substances.
Most are used as flavouring agents but a few have medicinal value.
Infusions
(i) Fresh Infusions are made by extracting vegetable drugs for a short time
with cold or boiling water (making of tea). They quickly deteriorate as a
result of microbial contamination and therefore must be used within 12
hours.
(ii) Concentrated infusions are made by cold extraction with 25 %
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alcohol. The alcohol preserves the product for an indefinite period.
Biphasic liquid dosage forms
They are sub categorized into two different forms namely as –
I) Emulsion
II) Suspension
 Emulsion is a biphasic liquid preparations containing two immiscible liquid
(Continuous Phase & dispersed phase) made missicible.
 The liquid which is converted into minute globules is called as dispersed phase
& the liquid in which the globules are dispersed is called the continuous phase
Two Immiscible Liquids
dispersed phase
continuous phase
Dispersed Phase
(Internal phase)
Continuous Phase
(External phase)
 An emulsion is a thermodynamically unstable system consisting of at least two
immiscible liquid phases one of which is dispersed as globules in the other liquid
phase stabilized by a third substance called emulsifying agent.
The globule size in emulsion varies from 0.25 to 25 µm.
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Types of emulsions
28
Simple type
 Water in oil (w/o)
 Oil in water (o/w)
Depending on globule size
 Micro emulsion:
Fine emulsion: have a milky appearance.
Special type
 Multiple emulsion (w/o/w, o/w/o)

Water in oil (w/o)
29




In this types of emulsion water is dispersed phase & oil is
continuous phase
w/o types of emulsion generally meant for External use.
Examples are butter, lotions, creams etc.
In rare case they are used internally.
Water is dispersed phase
Oil is continuous phase
Oil in water (o/w)
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
In this types of emulsion oil is dispersed phase & water is continuous phase

o/w types of emulsion meant for both Internal use & External use.


Examples for internal use are Vitamin A in corn oil, liquid paraffin in water
etc.
Examples for External use are Benzyl benzonate emulsion.
Oil is dispersed phase
water is continuous phase
Micro Emulsion
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


These are clear dispersions of o/w or w/o in which the globules have small
size like as a 10nm or 0.01 µm..
Being cleared products micro emulsion are more popular now a days.
Micro emulsions are thermodynamically stable optically transparent ,
mixtures of a biphasic oil –water system stabilized with surfactants.
Multiple emulsion
These are emulsion with in emulsion &
designated as w/o/w or o/w/o.
The drugs that is incorporated in the
innermost phase must cross two phase
boundaries before getting absorbed.
It is generally used in oral sustained release
or intramuscular therapy.
Suspension
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


are the biphasic liquid dosage forms of
medicament in which finely divided
solid particles ranging from 0.5 to 5
micron are dispersed in a liquid or
semisolid vehicle with aid of single or
combination of suspending agent.
In which solid particles acts as disperse
phase where as liquid vehicle acts as
continuous phase
The external phase (suspending
medium) is generally aqueous in some
instance (oral use), may be an organic or
oily liquid for non oral use.
Advantage of suspension
 Suspension can improve chemical stability of certain drug. E.g.
Procaine penicillin
 Drug in suspension exhibits higher rate of bioavailability than
other dosage forms.
Solution > Suspension > Capsule > Compressed Tablet >
Coated tablet
 Duration and onset of action can be controlled. E.g. Protamine
Zinc-Insulin suspension.
 Suspension can mask the unpleasant/ bitter taste of drug. E.g.
Chloramphenicol
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Difference between flocculated & deflocculated suspension
Flocculated Suspension
Deflocculated suspension
Particles form loose aggregates &
forms network like structure.
Particle exist as separate entities.
Particles experience attractive forces.
Particles experience repulsive forces.
Supernatant liquid is clear.
Supernatant liquid is cloudy.
The rate of sediment is high.
The rate of sediment is slow.
Sediment is rapidly formed.
Sediment is slowly formed.
sediment are loosely packed, hence
hard cake is not formed.
Sediments are closely packed, hence
hard cake is formed.
The sediment is easy to redisperse on
shaking.
Sediment is difficult to redisperse on
shaking. (due to formation of hard
cake)
Bioavailability is comparatively less.
Bioavailability is relatively high.
The suspension is not pleasing in
appearance.
The suspension is pleasing in
appearance.
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Semisolid dosage forms
35



Semisolid dosage forms meant for external application
Semisolid dosage forms subcategorized are asI) ointment
II) creams
III) paste
IV) Jellies
V) Suppositories
The suppositories are also included in this category but it is a
unit dosage forms.
Creams
According to the FDA’s, “…a cream is an emulsion usually containing >
20% water and volatiles and/or < 50% hydrocarbons, waxes, or polyols
as the vehicle.”
Creams are thicker than lotion (o/w- Hydrophilic creams or w/oHydrophobic creams ) and Softer than ointments/paste and are preferred
as easy removal from containers and good spreadability over the
absorption site
These are viscous semisolid emulsions which are meant for external
use.
Cream is divided in to two types namely as
I) Aqueous creams
II) Oily creams
In case of aqueous creams the emulsions are o/w type & it is
relatively non greasy.
In case of oily creams w/o type & it is relatively greasy.
Stay short time on skin than ointment.
36Healing power and absorption is more than ointment
Ointment
Ointment are semisolid preparation meant for application to skin or
mucous membrane for their protective or emollient (softening or
soothing ) properties
According to the FDA’s, “…a ointment is an emulsion or suspension
usually containing < 20% water and volatiles and/or > 50%
hydrocarbons, waxes or polyols as the vehicle.”
Non-porous - hence perspiration cannot escape through it.
Pastes
Semisolid preparations intended for external application to skin.
Generally very thick & stiff.
Do not melt at ordinary temperature & thus forms a protective coating
over the area where they are applied.
They are porous so the perspiration (sweat)can escape through it.
Pastes are differ from ointment as they contain a high proportion of
37 finely powdered medicaments (20-50 %) . So less greasy then ointment
Jellies
are transparent or translucent, non greasy, semi solid preparations
mainly used for external application to skin.
The substance like gelatin, starch, tragacanth, sodium alginate &
cellulose derivatives are used for the formulation of jellies. Cross
linking i.e. there.
Suppositories:
Semisolid formulation for insertion to body cavities (vagina, urethra etc).
Poultice: a soft, moist mass of material applied to the body to relieve
soreness and inflammation and kept in place with a cloth.
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Pharmaceutical Ingredients/Additives/ Non active part of drug
Definition:
An excipient is a pharmacologically inactive substance formulated
alongside the active pharmaceutical ingredient of a medication.
Ideal properties of Excipients
Feasible
No interaction with drug
Excipients
Cost
effective
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Stable
Pharmacologically inert
Purposes served by excipients:
Provide bulk to the formulation in case of small dose of API
Facilitate drug absorption or solubility and other pharmacokinetic
considerations.
Aid in handling of “API” during manufacturing .
Provide stability and prevent from denaturation . etc.
Categories of Pharmaceutical Excipients
1. Fillers/diluents/ bulking agents:
 Add volume and/or mass to a drug substance.
Used in tablets and capsules.
Dibasic calcium phosphate are used popularly as fillers. Other
examples of fillers include: lactose (most commonly used but exhibit
Millard reaction), anhydrous lactose (stable), sucrose, glucose,
mannitol (chewable tablet), sorbitol, calcium carbonate
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Binders:
Binders hold the ingredients in a tablet together .
Binders ensure that tablets and granules can be formed with
required mechanical strength.
May be
1. Solution binders: are dissolved in a solvent (for example water or
alcohol can be used in wet granulation processes). Examples include
gelatin, polyvinylpyrrolidone, starch, and polyethylene glycol.
2. 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: methyl cellulose, polyvinylpyrrolidone and
polyethylene glycol.
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Disintegrants
Facilitate breakup of tablets and contents of capsules into smaller
particles for quick dissolution when it comes in contact with water in the
GIT.
Examples: Sodium starch glycolate, Microcrystalline cellulose
(MCC), Croscarmellose sodium, Crospovidone, Ac-Di-Sol(Sodium
Carboxy methyl cellulose Na-CMC)
Coating Agent : for tablet coating
Layer of coating material is applied to the surface of a dosage form
Function of coating agents: Protection form moisture (film coating),
taste masking (sugar coating), protection for gastric pH (enteric coating)
elegance, ease of swallowing, identification etc.
Examples: Carboxy methyl cellulose sodium (CMC), Carnauba
Wax, Cellulose acetate, phthalate (CAP/used in enteric coating),
42Zein & Shellac (sealing agent).
Lubricants, Antiaherent and Glidants
– Lubricants are intended to reduce friction during tablet
ejection between the walls of tablet and die cavity by
interposing an intermediate layer. Stearates, waxes
– Antiaherent prevent adhesion of the tablet materials to the
surface of dies and punches, reduce inter particle friction and
may improve the rate of flow of the tablet granulation. Eg talc
– Glidants are intended to promote flow of granules or powder
material by reducing the friction between the particles. Eg.
Silicon dioxide (Cab-O-Sil, Aerosil in 0.25-3% conc)
Preservatives
protects the product against microbial proliferation/growth and
maintain the stability of product during its self life. Methylparaen,
43Ethyl parabens, Propylparaben, Butylparaben, Benzoic acid and its
salts
Antioxidant:
An antioxidant is a molecule that inhibits the oxidation of other
molecules.
a. Oxidation: Oxidation is defined as loss of electrons or addition
of oxygen.
b. Auto-oxidation: It is a reaction with oxygen of air which occurs
spontaneously without other factors.
c. Pre-oxidants: These are substances catalyze oxidation process
e.g., metals, some impurities.
Preservation against oxidation
Addition of Primary antioxidant: act by interfering with the
propagation step of auto-xidaton process. e.g.,
 Natural antioxidant: Tocopherol (Vitamin E), Gallic acid,
 Synthetic antioxidant : Sodium Metabisulfite (Water soluble)
and Butylated hydroxyl anisol/BHA & Butylated hydroxyl
44
tolune /BHT (Oil soluble)
Sweetening agents
added primarily to chewable tablets/in liquid formulations designed for oral
administration specifically to increase the palatability of the therapeutic
agent.
Example: natural sugar like Sucrose, Lactose, Sorbitol, Mannitol
(extensively used in chewable tablets ) etc and artificial sugar Saccarine,
Aspertame.
Flavouring agents
are used to impart pleasant, smell to the preparation and to mask specific
type of taste of the preparation, thus make them more palatable and improve
patient acceptance. Ex.
pineapple, clove, lemon oil, orange, rose,vanilla, Menthol.
Coloring agents
impart the preferred color to the formulation.
Example: 1.White: Titanium dioxide (Opacifier) 2. Blue :Brilliant blue
,Indigo carmine 3. Red :Amaranth Carmine 4.Yellow: saffron 5.Green45
Erithrosine, 6.Brown: caramel
Solvent
Used can dissolve a solute
Can be Polar and Non polar
Polar solvent dissolves polar compound best and non polar solvent
dissolves non polar compound best.
The first choice for a solvent is water in which a drug is freely
soluble.
Non Aqueous Solvent May be nonaqueous but water miscible
(e.g. Ethanol, propylene glycol, glycerol, sorbitol) and Nonaqueous
and water immiscible vehicle e.g. vegetable oils (used for parenteral
as well as skin preparation)
Co-solvent
Co-solvents are defined as water-miscible organic solvents that are
used in liquid drug formulations to increase the solubility of poorly
water soluble substances or to enhance the chemical stability of a
46drug. Eg. Ethanol, propylene glycol, glycerol, sorbitol
Chelating agent
Chelating agents are stabilizing agents that are capable of forming
complexes with the metalic impurities
EDTA: ethylene diamine tetraacetate is used for the estimation of
metals ions .
Calcium Disodium Edetate: it is used in the treatment of heavy
metal poisoning mostly caused by lead.
Buffering agent
resist any change in pH of solution upon addition of an acid or an
alkali.
Most of the buffering system are based on carbonate, citrates,
gluconates , lactates, phosphates, or tartrates.
Viscosity Enhancers
Hypromellose, hydroxyethylcellulose, polyvinyl alcohol, povidone,
47
dextran, carbomer 940.
Isotonicity Adjusters
Sodium chloride, potassium chloride etc
Humectants
Added in externally use preparation
Retains the moisture of skin and prevent the drying.
Eg. ethylene glycol, polyethylene glycol (PEG), glycerin.
Surfactants :
Compounds that lower the surface tension (or interfacial tension)
between two liquids or between a liquid and a solid and increase
the solubility. They are also known as surface active agents.
A surfactant contain lipophilic region (tail) and hydrophilic region
(head/ charge present here)
Types of surfactants : There are of four types of surfactants
a) Anionic surfactants: here the hydrophilic region is negatively
Sodium lauryl sulphate, Ammonium
48charged i.e. an anion). Eg.
lauryl sulphate
2. Cationic surfactant (here hydrophilic region is positively
charged i.e. a cation)
Cetyl trimethyl ammonium bromide ( cetrimide ) - is an effective
antiseptic agent against bacteria and fungi
Benzylkonium chloride
3. Non-ionic surfactants :
Tween 80 (Polysorbate 80 / polyoxyethylene sorbitol monooleate)is an excipient that is used to stabilize aqueous formulations of
medications for parenteral administration
Span ( sorbitan ester of lauric acid )
4. Amphoteric surfactant :
Lecithin and N-dodecyl alanine.
49
First pass Metabolism
The first-pass effect is the term used for the hepatic metabolism of
a pharmacological agent when it is absorbed from the gut and
delivered to the liver via the portal circulation.
The greater the first-pass effect, the less the agent will reach the
systemic circulation when the agent is administered orally
Where ?
Liver
Gut wall
Gut Lumen
Result ?
Low bioavailability.
Short duration of action (t ½).
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Routes of administration
A drug will produce its action only when it enters the body, tissue or
cells (i.e. site of action)
Entrance through which a drug is delivered is called the route of
drug administration.
Classification
51
1. ORAL ROUTE
The Most common route and Drug is given through oral cavity
absorbed from the gastro-intestinal tract
Advantages
Safe, Convenient- self- administered, pain free, non-invasive and
easy to take
Preparations are economical as compared to other parenteral routes
No need for sterilization
Disadvantages
Slow absorption slow action - can not used in emergency
 Irritable and unpalatable drugs (e.g. paraldehyde)- nausea and
vomiting
 Cannot be used Unco-operative, vomiting and unconscious
patients
Some drugs destroyed by digestive juices (e.g. penicillin G,
52
insulin)
Sometimes inefficient drug absorbed, some drugs are not absorbed
like streptomycin
First-pass effect- Due to Biotransformation in liver (e.g.,
nitroglycerin, testosterone, lidocaine).
 Food–Drug interactions and Drug-Drug interactions
53
2. SUBLINGUAL OR BUCCAL
The tablet or pellet containing the drug is placed under the tongue
(sublingual) or crushed in the mouth and spread over the buccal mucosa.
The drug is absorbed through the buccal mucosa. e.g. nitroglycerine,
isoprenaline, clonidine, nifedipine.
Advantages
Disadvantages
Drug absorption is quick
Unpalatable & bitter drugs con
not administered
Quick termination
Irritation of oral mucosa
First-pass avoided
Large quantities not given
Can be self administered & Economical
Few drugs are absorbed, small
dose
54
3. RECTAL ROUTE
The drug containing dosage form is either inserted or put into the
rectum as suppositories or retention enema.
One part of the absorbed drug passes to the liver (superior
haemorrhoidal vein drains into the hepatic portal vein which flows to
liver), another part to the systemic circulation (drug passes through
inferior and middle haemorrhoidal veins drain directly into the systemic
circulation via the inferior vena cava).
Advantages: this route can also be used
Drugs having bad taste or odour and degrades in acidic pH of the
gastric juice
Patient is having recurrent vomiting.
Disadvantages: Inconvenient and embarrassing route
Absorption is slower, irregular and often unpredictable.
55
4. Inhalation
The drug is administered through nose or mouth, carried by the
air to reach the lung. The alveoli are rich with capillary vessels. The
drug is diffused into the blood stream. Thus systemic action is
obtained.
Advantages:
(i) Absorption takes place from the vast surface of alveoli - hence
action is very rapid.
5. Nasal
The drug is administered as snuff or spray or nebulized solution
in the nose; where the drug penetrates the nasal mucous membrane
to reach the blood.
Advantages:
(i) The drug can avoid digestive juices and liver.
56
6. Parenteral
(Par- beyond, enteral- intestinal) Routes of drug administration
other than oral route are known as parenteral route.
This refers to administration by injection which takes the drug
directly into the tissue fluid or blood without having to cross the
intestinal mucosa and subsequently liver.
a) Intradermal (I.D.) (into skin)
b) Subcutaneous (S.C.) (into subcutaneous tissue)
c) Intramuscular (I.M.) (into skeletal muscle)
d) Intravenous (I.V.) (into veins)
e) Intra-arterial (I.A.) (into arteries)
f) Intrathecal (I.T.) (cerebrospinal fluids )
g) Intraperitoneal (I.P.) (peritoneal cavity)
h) Intra - articular (Synovial fluids)
57
Advantages
high bioavailability
Rapid action (emergency)
No first pass metabolism
Disadvantages
 Infection
Sterilization.
Invasive
assistance require
Suitable for
Pain
Vomiting &unconsciousness Needs skill
 Irritant & Bad taste drugs.
Anaphylaxis
No gastric irritation
 Expensive
No food-drug interaction
Dosage form:
Vial or ampoule
58
A) Intra-dermal injection
drug is injected into the
dermis of skin.
route is employed for
specific purpose only like
BCG vaccine, sensitivity
testing of drugs.
B) Subcutaneous injection

The drug is injected under the skin. The drug is deposited in
the loose subcutaneous tissue which is richly supplied by nerves
(irritant drugs cannot be injected)
oily solutions or aqueous suspensions can form a depot which will
release drug slowly for a prolonged period.
Eg. e.g. Insulin injection.
C) Intramuscular injection
The drug is injected in one of the large skeletal muscles59
deltoid, triceps, gluteus maximus, rectus femoris etc.
Advantages:
Muscle is less richly supplied with sensory nerves, hence mild
irritants can be injected.
Muscle is more vascular hence absorption is faster than
subcutaneous route.
It is less painful.
Depot preparations can be injected by this route and the action of
the drug may be prolonged.
Disadvantages:
Since deep penetration is needed hence self-medication is not
possible.
Large volume cannot be given.
e.g. Low volume injections - Vitamin A, hydrocortisone acetate,
tetanus toxoid, antibiotic etc.
60
D) Intravenous
The drug is injected as a bolus or infused slowly over hours in one of
the superficial veins (generally brachial vein).
Advantages:
The drug directly reaches the blood stream and effect is produced
immediately, hence, this route can be used in emergencies.
The inside of the veins is insensitive and drug gets diluted with
blood quickly, therefore, even highly irritant drugs can be injected
intravenously.
Large volumes can be infused (e.g. normal saline).
It is useful in unconscious patients.
Desired blood concentration can be achieved.
Disadvantages:
Drugs that precipitate in the blood cannot be administered. Only
aqueous solution can be administered.
If the needle puncture the vessel (i.e. extra vasation) then
61thrombophlebitis of the injected vein and necrosis of the adjoining
tissues may occur.
No drug can be given in depot form - so the action is not prolonged
compared to other parenteral administrations.
Once administered, withdrawal of the drug is not possible.
E) Intra-arterial
A drug is injected into an artery. The effect of a drug can be
localized in a particular organ or tissue by choosing the appropriate
artery. Anticancer drugs are sometimes administered by this route.
F) Intra-peritoneal
In this route a drug is injected into the peritoneal cavity. By
this route fluids like glucose and saline can be given to children.
62
G) Intra – articular
injections of antibiotics and corticosteroids
are administered in inflammed joined
cavities
by
experts.
example:
hydrocortisone in rheumatoid arthritis
7. Transdermal/ cutaneous route
The dosage form is applied or placed on the skin and the drug
penetrates the skin to reach the blood i.e. cutaneous route is meant
for systemic absorption.
Advantages:
(i) Highly lipid soluble drugs can be applied over the skin for slow
and prolonged absorption.
(ii)The liver is bypassed through this route.
Disadvantages:
(i) Absorption is very slow. So it cannot be used in emergency
situation.
(ii)Water soluble drugs are minimally absorbed through the skin.
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8. Topical Routes of Administration
Application of a drug directly to the surface of the skin
Includes administration of drugs to any mucous membrane
eye
– vagina
Nose
– urethra
ears
– colon
lungs
Dose forms for topical administration include:
Skin:
creams
 ointments
• Eye or ear:
lotions
– solutions
gels
– suspensions
transdermal patches
– ointments
• Nose and lungs:
64
– sprays and powders