pharmaceutical Excipients

1. SUSPENDING & EMULSIFYING AGENTS
Dr.RLC SASIDHAR
Associate Professor

2. • A Pharmaceutical suspension is a disperse system in
which internal phase is dispersed uniformly as finely
divided insoluble particles throughout the external
phase.
• The internal phase consisting of insoluble solid particles
having a specific range of size which is maintained
uniformly throughout the suspending vehicle with aid of
single or combination of suspending agent.
• The external phase (suspending medium) is generally
aqueous in some instance, may be an organic or oily
liquid for non oral use.

3. Suspending agents
• Suspending agents are substances that are used to keep
finely divided insoluble materials suspended in a liquid
media by preventing there agglomeration (coming together)
and by imparting viscosity to the dispersion media so that
the particles settle more slowly.
• Care must be taken when selecting a suspending agent for
oral preparations as the acid environment of the stomach
may alter the physical characteristics of the suspension and
therefore the rate of release of the drug from suspension.
• A good suspension should have well developed thixotropy.

4. • Most suspending agents perform two functions i.e.
besides acting as a suspending agent they also imparts
viscosity to the solution. Suspending agents form film
around particle and decrease interparticle attraction.
• Suspending agents also called thickening agents are
used to stabilize suspensions .
• Suspending agents are hydrophilic colloids i.e.
substances that spontaneously form colloidal dispersions
with water because of an affinity between the
dispersed particles and the dispersion medium.

5. • They help in lowering the sedimentation rate of
particles in suspension.
• The sedimentation rate is slowed down by increasing
the viscosity of liquid vehicle, and slowing down settling
in accordance to stokes law.
• They usually prevent caking at the base of an
suspension . It could be resuspendend by agitation.
• Examples : bentonite, carbomer, tragacanth, kaolin,
carboxymethyl cellulose sodium etc.

6. Typesof SuspendingAgents
1. NATURAL AGENTS
• This class consists of those from.
a. Animal source eg Gelatine
b. Plant source eg. Accacia, Tragacanth, Starch, sea weed
(Alginates)
c. Mineral sources.eg Bentonite, Kaoline
2. SEMI-SYNTHETIC AGENTS
• These consist of substituted cellulose (minerals) eg.
Hydroxyethylcellulose , Sodium Carboxymethylcellulose ,
methylcellulose, Microcrystalline cellulose
3. SYNTHETIC AGENTS
• They are synthetic polymers eg carboxypolymethylene
(carbopol), Polyvinyl Alcohol, Polyvinyl Pyrolidone iodine
complex (PVC)

7. Types of suspending agents
A. POLYSACCHARIDES.
B. INORGANIC SALTS.
C. SYNTHETIC C
POLYSACCHARIDES.
• The official suspending agents were natural
polysaccharides but nowadays semi synthetic
compounds are increasingly used. Following are some
examples of it
• Acacia
• Tragacanth
• Starch
• Alginates
• Xanthamn Gum

8. • Is dried exudates from Acacia
senegal which occur as round
ovoid colorless or white
powder.
• Not as good suspending agent
but its protective colloidal
property.
• Because of Stickiness it is
used externally.
• It is useful in preparation of
tinctures.
Acacia
• As a thin, white or yellowish
white, ribbon like flakes.
• It forms viscous aqueous
solutions.
• Stable over pH 4 to 7.5
• Used externally and internally.
Acacia
Tragacanth

9. Starch
• Starch is a white, granular, organic chemical that is
produced by all green plants.
• Starch is a tasteless powder that is insoluble in cold
water , alcohol etc.
• Most of commercial starch is made from corn, wheat
and potato.
Inorganic Salts
The following are examples of inorganic salts
• Clay
• Bentonite
• Aluminum magnesium silicate
• Aluminum hydroxide

10. Inorganic Salts
• Is subtype of montmorillionite clays, they
hydrate readily absorbing up to 12 times
their weight of water particularly at
elevated temperatures.
• The gels formed are thixotropic in nature
so act as good suspending agent.
• Insoluble flakes that disperse and swell
readily in water.
• Use in concentration of 5% both
internally and externally
• Stable at pH 3.5 to 11.
• They have high thixotropic and
plasticity but presence of salts can
alter their properties.
Bentonite
Magnesium
aluminum silicate

11. Synthetic Suspending Agents
These were introduced to over come various problems
occurring from natural products. Following are its
examples
Carbomers
Colloidal silicon dioxide.
• This material is totally copolymer of
acrylic acid and allyl sucrose.
• Used for external preparation.
• When adjusted to pH between 6 to
11 becomes highly viscous.
• When dispersed in water they formed a
three dimensional network.
• It used as thickening agent for non
aqueous suspension.
• It obtain from silicon dioxide.
• Cannot be easily dispersible.
Carbomer
Colloidal
silicon dioxide

13. • 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.
• An emulsion is a dispersion in which the dispersed
phase is composed of small globules of a liquid
distributed throughout a vehicle in which it is
immiscible.
• The dispersed liquid is known as the Internal or
Discontinuous phase.
• whereas the dispersion medium is known as the External
or Continuous phase

14. Emulsifying Agents
• They are the substances added to an emulsion to
prevent the coalescence of the globules of the
dispersed phase. They are also known as emulgents or
emulsifiers.
• They help in formation of emulsion by three
mechanisms.
1. Reduction in interfacial tension – thermodynamic
stabilization
2. Formation of a rigid interfacial film – mechanical
barrier to coalescence
3. Formation of an electrical double layer – electrical
barrier to approach of particles.

15. Pharmaceutically acceptable emulsifiers must also :
• Be stable .
• Be compatible with other ingredients .
• Be non – toxic .
• Possess little odor , taste , or color .
• Not interfere with the stability of efficacy of the active
agent

16. Classification of Emulsifiers
• Synthetic Surface active agents
• Semi synthetic and natural Hydrophilic colloids
• Finely divided solid particles
1. Synthetic surface active agents
• Reduce interfacial tension and make the emulsion
thermodynamically more stable.
• To reduce the interfacial tension Oil droplets are
surrounded by a coherent monolayer of the
surfactant which prevents coalescence.
• If the emulsifier is ionized, the presence of strong
charge may lead to repulsion in droplets and hence
increasing stability.
• Adsorbed at oil/water interface to form protective
monomolecular film

17. Anionic surfactants
SOAPS
1) Monovalent
• E.g. potassium, sodium, ammonium salts of oleic acid .
• They are soluble in water and are good o/w emulsifying
agents.
Disadvantages :
• They are irritating to the GIT.. So they are useful only for
external use emulsions.
• They have a high pH, so cannot be applied on broken skin.
2)Organic Soaps
• Triethanol amine soaps of fatty acids give o/w emulsion.
• They are used for external use emulsions.
• They are less alkaline as compare to monovalent/polyvalent
soaps so they can be used on broken skin.
SULPHATES
• They are neutralized esters of sulphuric acid and fatty
alcohols. Poor o/w E.A if used alone.
• They can be used as auxiliary emulsifying agents. E.g Sodium
lauryl sulphate

18. Cationic surfactants
• They are mainly used in external preparations.
Quaternary ammonium compounds such as cetrimide,
benzalkonium chloride and benzethonium chloride are
examples of important cationic surfactants.
• These compounds besides having good antibacterial
activity are used in combination with secondary
emulsifying agents to produce o/w emulsions for
external application.

19. NON IONIC SURFACTANTS
• They are the class of surfactants widely used as
emulsifying agents.
• They are extensively used to produce both o/w and w/o
emulsions for internal as well as external use.
Advantages :
• They are not effected by pH change and presence of
electrolytes.
• They also show low irritancy as compared to other
surfactants.
Most commonly used nonionics are
• glyceryl esters (auxillary E.A)
• sorbitan fatty acid esters (spans) w/o
• polyoxyethylene derivatives of sorbitan fatty acid
esters (Tweens or polysorbates) o/w

20. 2.Semi Synthetic and Natural Surface Active Agents
• Also known as Hydrocolloid Emulsifying agents
• Provide a protective sheath (Multi-molecular films
)around the droplets
• Impart a charge to the dispersed droplets ( so that they
repel each other
• Swell to increase the viscosity of the system ( so that
droplets are less likely to change.)

21. • Semisynthetic Includes mainly cellulose derivatives like
sodium carboxymethyl cellulose, hydroxyl propyl
cellulose and methyl cellulose.
• They are used for formulating o/w type of emulsions.
• They primarily act by increasing the viscosity of the
system. e.g., methyl cellulose, hydroxypropyl cellulose
and sodium carboxy methyl cellulose.
• Natural -Plant origin: Polysaccharides
(Acacia, tragacanth, agar, pectin, lecithin)
• Animal origin :Proteins ( Gelatin) Lecithin, Cholesterol
Wool fat, Egg yolk

22. 3. Finely Divided Solid Particles
• Also known as Particulate films
• Form a particulate "film“ around dispersed particles.
• These particles rely on adsorption to interfaces and like the
hydrophilic colloids, function by forming a physical barrier to
coalescence.
• Finely divided solid particles that are wetted to some degree by
both oil and water act as emulsifying agents. This results from
their being concentrated at interface, where they produce a
particulate film around the dispersed droplets to prevent
coalescence
• Colloidal Clays : Bentonite, Veegum ( Magnesium Aluminium
silicate), Magnesium trisilicate

24. • Semi solids are the topical dosage form used for the
therapeutic, protective or cosmetic function. They may
be applied to the skin, or used nasally, vaginally, or
rectally…
Advantage of semi-solid dosage form:
• First pass gut and hepatic metabolism is avoided.
• Local action and Site specific action of drug on affected
area.
• Convenient for unconscious patient or patient having
difficulty on oral administration.
• Suitable dosage form for bitter drugs.
• More stable than liquid dosage form or used nasally,
vaginally, or rectally…

25. Disadvantages of semi-solid dosage form:
• There is no dosage accuracy in this type of dosage form
• The base which is used in the semi-solid dosage form can
be easily oxidized.
• May cause staining.
• Application with finger may cause contamination.
• Physico-chemically less stable than solid dosage form.
• May cause irritation or allergy to some
Ideal Properties of Semisolids
• Smooth texture
• Elegant in appearance
• Non dehydrating
• Non gritty
• Non greasy and non staining
• Non irritating
• Do not alter membrane / skin functioning

26. Excipients used in Preparation
• Bases
• Preservative
• Humectants
• Antioxidants
• Emulsifier
• Gelling agent
• Permeation enhancer
• Buffers

28. 1. BASES
• It is one of the most important ingredient used in
formulation of semisolid dosage form. Ointment bases
do not merely act as the carriers of the medicaments,
but they also control the extent of absorption of
medicaments incorporated in them.
IDEAL PROPERTIES OF A BASE
• They should be Inert, non-irritating and non-sensitizing.
• Compatible with skin pH and the drug.
• Good solvent and/or emulsifying agent.
• Emollient, protective, non-greasy and easily removable.
• Release medicament readily at the site of application.

29. Selection Criteria of ointment base
• Desired release rate of the drug substance from the
ointment base.
• Rate and extent of topical or percutaneous drug
absorption.
• Stability of the drug in the ointment base.
• Effect of the drug on the consistency of base.
• Easy removal of base on washing.
• Characteristic of the surface to which
it is applied.

30. • Ointments bases are classified by the USP into four
general groups:
A- Hydrocarbon Bases (oleaginous bases)
(Petrolatum , Paraffin, Lanolin…..)
B- Absorption bases (cold cream, anhydrus lanolin …)
C- Water- Removable bases ( oil in water)
D- Water- Soluble bases (polyethylene glycol)

31. Oleaginous( Hydrocarbon)Bases
• They consist of a combination of more than one oleaginous
material such as water insoluble hydrophobic oils and fats .
Disadvantages:
• Greasy, sticky-non washable
• Retain body heat
• Do not increase absorption
• Prevent drainage on oozing area.
• They are anhydrous, do not absorb water & insoluble in water.
• Examples:
1. Hydrocarbons: Paraffin wax, Soft paraffin, Liquid paraffin
2. Vegetable oils and animal fats: Peanut oil, Coconut oil, Lanolin,
Bees wax
3. Hydrogenated & sulfated oils: Hydrogenated castor oil,
Hydrogenated & sulfated castor oil.
4. Acids, Alcohols & Esters: Stearic acid, Stearyl alcohol, Isopropyl
Myristicate.
5. Silicones: Dimethyl polysiloxanes

32. A) Soft paraffin (Petrolatum)
• This is purified mixture of semisolid hydrocarbons obtained from
petroleum.
Types
1. Yellow soft paraffin: M.pt=380C, used in ophthalmic ointments.
2. White soft paraffin: M.pt=560C, obtained from bleaching Yellow
soft paraffin.
B) Hard paraffin:
• Purified mixture of solid hydrocarbons obtained from petroleum.
USE- harden/soften ointment base

33. 2. Absorption (Emulsifiable) Base
• Absorption bases are also known as emulsifiable bases
because they initially contain no water but are capable of
taking it up to yield W/O and O/W emulsions.
General Characteristics:
• These are less occlusive than the hydrocarbon bases.
• Incorporation of aqueous solution is possible.
• Easier to spread.
• They hydrate the stratum corneum.
• Difficult to wash from the skin.

34. 1. Wool fat(Anhydrous lanolin)
• This is fat from wool of sheep. Can absorb 50% water of
its weight.
USE: ointment base preparation, ophthalmic ointments.
2. Wool alcohol: Wool fat is alkalized to obtain
cholesterol & alcohol.
USE: Emulsifying agent in preparation of W/O emulsions.
3. Bees wax: Wax from honey comb of bees.
• 2 types- yellow & white bees wax USE: stiffening agent
in paste & ointments.

35. 3. Emulsion Bases / Water Removal Bases
• Emulsion bases are either O/W or W/O emulsions,
resembling creams.
• These are water washable, easier to remove.
• Non greasy and non occlusive.
• Cane be diluted with water or aqueous solutions.
• Better compliance, spreads readily, evaporating water
soothens the inflamed tissue.
• Examples are cold cream type, Hydrous lanolin,
Hydrophillic ointment.

36. 4. Water Soluble Bases
• These are greaseless ointment bases which include both
anhydrous and hydrous non emulsion bases which are water
soluble and contain no oil phase.
• Unlike other bases they contain only water soluble
components (Greaseless Bases)
• They are completely water washable
• Aqueous solutions can not be incorporated efficiently
because they soften greatly with water addition.
• Mostly used for incorporation of solid substances.
• Exapmles: Polyethylene Glycol Ointment, Polybase etc.

37. Carbo waxes (Macrogols/ Polyethylene glycols)
• General formula CH2OH. (CH2OCH2 )n . CH2OH
• These are mixtures of polycondensation products of ethylene
oxide and water
• Average Molecular weight is represented by numbers
Macrogols 200, 300, 400 -- viscous liquids
Macrogol 1500 -- greasy semi solid
Macrogols 1540, 3000,4000, 6000 -- waxy solids
Macrogols Properties:
• Non-toxic and non-irritating
• pH – 4 to 7.5
• Can be sterilised by heat (solids – dry heat, liquids –
autoclave)
• Water soluble, non-volatile and inert substances.

38. GELLING AGENTS

39. • Gelling agents are the substances that forms gel
after dissolving in a liquid phase as colloid
mixture.
• Basically these are organic hydrocolloids/
hydrophilic inorganic substances that can be
obtained from both natural and synthetic sources.
• 1. Natural gelling agents – Gum tragacanth, starch,
pectin, gelatin, clays, cellulose derivatives, etc.,
• 2. Synthetic gelling agents – Sodium alginate,
carbomer, poly vinyl alcohol, etc.,

40. 1.Tragacanth
• Used for preparations of Lubricating, Medicated &
Contraceptive Jellies.
• Concentrations used for Lubricating (2 to 3%) &
Dermatological vehicle (5%).
• Tragacanth is poorly wettable . On addition to water, lumps
are formed which is difficult to disperse.
• Dispersing agent is generally used to get a homogenous
product.
• Alcohol, glycerol or volatile liquids are used as dispersing
agent
Disadvantages :
• Obtained from natural sources, so vary in viscosity
• After evaporation, the film left on the skin tends to flake
• Can’t be stored for longer time
• Prone to microbial growth.

41. 2. Pectin
• Good gelling agent suitable for acid products
• Used in many preparations including edible Jellies
• Glycerine is used as dispersing agent & humectant
• Pectin jelly is good medium for bacterial growth, add
preservative
Storage:
• Well closed container to prevent loss of moisture by
evaporation.
3. Gelatin :
• Insoluble in cold water (swells and soften) and Soluble in
hot water
• 2% gelatin forms jelly on cooling.
• Stiff medicated Jellies can be prepared (15%)
• Melted before use and after cooling to desired temperature,
• applied with a brush.
• Suitable preservative is required.

42. Sodium Aliginate :
• 1.5 to 2% Used as Lubricant gel & for dermatological
vehicle 5 To 10% is used.
• Viscosity can be increased by adding soluble calcium
salt
• Salting out is observed with high concentration.
• 2-4% alcohol, glycerine, propylene glycol are used as
dispersing agent.
Advantages over Tragacanth
• Available in several grades of standard viscosity.

44. • Solubilizers are incorporated in semi solid dosage forms so as to
solubilize insoluble liquids, insoluble organic material or oil
soluble ingredients.
Examples:
1. Cyclodextrins
• Cyclodextrins (cycloamyloses) are a family of compounds made
up of sugar molecules bound together in a ring (cyclic
oligosaccharides).
• Cyclodextrins are produced from starch by means of enzymatic
conversion.
• They are used in food, pharmaceutical, drug delivery, and
chemical industries, as well as agriculture and environmental
engineering.

45. • cyclodextrins are able to form inclusion complexes with
drugs by taking up the drug molecule or lipophilic
moiety of the molecule, into the central cavity in which
the polar cyclodextrin cavity is occupied by water
molecules.
• Cyclodextrins are used to
• Stabilization of light- or oxygen-sensitive substances.
• Modification of the chemical reactivity of guest
molecules.
• Fixation of very volatile substances.
• Improvement of solubility of substances.
• Modification of liquid substances to powders.
• Protection against degradation of substances by
microorganisms

46. Surfactants
• Surfactants are termed as surface-active agents also wetting
agents, emulsifying agents or suspending agents depending on
its properties and use.
• They are soluble in both organic solvents and water, so they
called amphiphilic.
• Surfactant can be classified based on charge groups present
in their head. A non-ionic surfactant do not have any charge
groups over its head.
• If the charge is negative, the surfactant is more specifically
called anionic and if the charge is positive, it is called
cationic.
• If a surfactant contains a head with two oppositely charged
groups, it is termed zwitterion.
• 1. Anionic surfactants
• 2. Cationic surfactants
• 3. Non-ionic surfactants
• 4. Zwitterionic/ amphoteric surfactants

47. • Surfactants are major constituents of pharmaceutical,
cosmetic, and food semisolid formulations, many of
which are emulsions, either oil in water (o/w) or water
in oil (w/o).
• They are included for their stabilizing, wetting,
solubilizing, detergent and penetration enhancing
properties.
• Surfactants are also used in formulation of cold cream,
cleansing cream, vanishing cream, shaving cream or any
media.