FINAL TERM : PHARMACEUTICS 101

DISPERSED SYSTEM
RHEOLOGY
Study the flow characteristics
DISPERSED SYSTEM:
Substance distributed (dispersed phase)
Vehicle (dispersing phase or medium)
CLASSIFICATION OF DISPERSION:
A. Coarse Dispersion- particle usually 10-50m in size (ex. Suspension)
B. Fine Dispersion- particle size is 0.5-10m
C. Colloids- particles are in colloidal range (1nm- 0.5m)
SUSPENSION
Coarse dispersion of finely divided drug particles called suspensoid distributed uniformly
throughout a vehicle in which the drug exhibits minimum degree of solubility
Needs a suspending agent to retard or slow down the setting of particles
Suspension may include:
GELS
LOTIONS
MAGMAS & MILK
MIXTURES
Suspending Agents:
Assist in the suspension of the dispersed phase
Amount of agent must not render the suspension too viscous to agitate or to pour
Examples:
Carboxymethylcellulose, methylcellulose, microcrystalline cellulose, polyvinyl
pyrolidone, xanthan gum & bentonite

HYDROPHILIC COLLIODS- increase the viscosity of water by binding water molecules

Ex: acacia, tragacanth, methylcellulose, carboxymethylcellulose
CLAYS- silicates that are anionic in aqueous dispersion; exhibit thixotrophy
Ex: bentonite, veegum, kaolin
OTHER AGENTS
Ex: agar, chondrus (carageenan), gelatin, pectin, gelatinized starch, xanthan gum

Types of Suspension:
A. GELS
- Semisolid preparation made up of small inorganic & large organic matter interpenetrated by
liquid
- fine dispersion of which particle size ranges (0.5- 10m)
- ex: Al(OH)3 -antacid, Tretinoin gel- exfoliate
JELENE or PLASTIBASE
A combination of mineral oils and heavy hydrocarbon waxes with a molecular
weight of about 1300
JELLIES
Are gels in which the structural content matrix contains a high proportion of liquid,
usually water
TERMINOLOGIES:
IMBIBITION- taking up a certain amount of liquid WITHOUT INCREASE IN VOLUME
SWELLING- taking up of liquid by a gel WITH AN INCREASE IN VOLUME; swelling of protein
gels is influenced by pH & the presence of electrolytes
SYNERESIS- interaction between particles of the dispersed phase becomes so great than
on standing, the dispersing medium is squeezed out in droplets and the gel shrinks; form
of instabilty in aqueous or non-aqueous gels
THIXOTROPHY- reversible-gel-sol formation with no change in volume/ temperature
XEROGEL- liquid is removed from a gel and only the framework remains
Ex: gelatin sheet, tragacanth ribbons, acacia tears

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CLASSIFICATION OF GELS:
Two general classification:
INORGANIC HYDROGELS
Two phase system such as Aluminum hydroxide gel and Bentonite magma
ORGANIC GELS
Single phase system and include gelling agents such as: carbomer and
tragacanth and those that contain an organic liquid , ex. plastibase
Other classification:
HYDROGELS
Ingredients that are dispersible as colloidals or soluble in wateer and include:
organic hydrogels, natural and synthetic gums and inorganic hydrogels
Ex: silica, bentonite, tragacanth, pectin, sodium alginate, methylcellulose, sodium
carboxymethylcellulose and alumina
ORGANOGELS
Hydrocarbons, animal and vegetable fats, soap base greases and the hydrophilic
organogels

Ex: Hydrocarbon-jellene, or plastibase

Preparation of Gels & Magmas
By freshly precipitating the dispersed phase
By direct hydration in water
B. LOTIONS
- liquid suspension intended for external application
Prepared by:
a. Trituration
porcelain mortar- unstainable substance,
glass mortar- stainable substance
Ex: calamine lotion- ZnO (active) Fe2O3
pinkish
color (aesthetic purpose)
b. Chemical reaction
Ex: white lotion- ZnSO4 + sulfurated potash ZnS
C. MAGMAS/ MILK
- Suspension containing bigger particles as compared to gels & lotions
- Gel mass has floccules of small distinct particles and classified as 2 phase system called
MAGMAS
- Mg(OH)2 milk of magnesia (white)
- Aqueous suspension of insoluble, inorganic drug
Prepared by:
By hydration
Ex. Hydration of Magnesium oxide
MgO + H2O Mg(OH)2
Chemical reaction
Milk of Bismuth is made by reacting bismuth subnitrate with nitric acid and
ammonium carbonate with ammonium solution and then mixing the resulting
solutions
2NaOH + MgSO4 Mg(OH)2 + Na2SO4 (direct hydration)
AEROSOLS
Pressured dosage forms containing one or more active ingredients upon actuation emit a
fine dispersion of liquid and/ or solid materials in gaseous medium
A colloidal dispersion of a gas in liquid
Factors which will render an aerosol effective:
Amount of propellant
Valve assembly
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Container
Particle size
Pressurized package- commonly used referring to the aerosol container or completed
product
Space sprays- aerosols used to provide an airborne mist
Ex: room disinfectant, room deodorizers and space insecticides
Surface sprays or surface coatings- aerosols intended to carry active ingredient to a
surface
Ex: dermatologic aerosols, pharmaceutical aerosols, personal deodorant sprays,
cosmetic hair lacquers and sprays, perfumes and cologne sprays, shaving lathers,
toothpaste, paint sprays, etc.
An aerosol is consists of 2 components:
The product concentrate
Is the active ingredient of the aerosol combined with the required adjuncts,
such as: antioxidants, surface-active agents and solvents, to prepare a stable
and efficacious product

The propellant
When the propellant is a liquefied gas or a mixture of liquefied gasses, it
frequently serves the dual role of propellant and solvent or vehicle for the
product concentrate
Examples of propellant:
Carbon dioxide
Nitrogen
Nitrous oxide
Fluorinated hydrocarbons:
Trichloromonofluoromethane
Dichlorodifluoromethane
Chlorpentafluoroethane
Monochlorodifluoroethane
Octafluorocyclobutane
CFC (chlorofluorocarbon)- phased out as propellant
AEROSOL SYSTEM
Space aerosols- usually operate at pressures between 30-40 psig at 70F and may
contain as much as 85% propellant
Surface aerosols- commonly contain 30-70% propellant with pressure between 25-55
psig at 70F
Foam aerosols- usually operate between 35-55 pig at 70F and may contain only 6-10 %
propellant
Two-phase system
Comprised of:
(1) liquid phase- liquefied propellant and product concentrate
(2) vapor phase
Three-phase system
Comprised of:
(1) layer of water immiscible liquid propellant
(2) layer of highly aqueous product concentrate
(3) vapor pressure
Vaginal & Rectal Aerosols
Example:
PROCTOFOAM
contains pramoxine hydrochloride and used to relieve inflammatory anorectal
disorder
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AEROSOL FOAMS
commercially available containing estrogenic substances and contraceptive
agents

Inhalation Aerosols
Examples:
Albuterol Inhalation (Proventil Inhalation Aerosol)- Beta-adrenergic
Beclomethasone Dipropionate (Beclovent Inhalation)- Adrenocortical, (Beconace)steroid
Cromolyn Sodium (Intal Inhaler)- Anti-asthma, Anti-allergy

Ipratropium Bromide (Atrovent)- Anti-cholinergic

Isoetharine Mesylate (Bronkometer)- Sympathomimetic, Bronchial asthma
Metaproterenol Sulfate (Alupent)- Sympathomimetic
Salmeterol Xinafoate (Serevent)- Beta-adrenergic agonist
Terbutaline Sulfate (Brethaire)- Beta-adrenergic agonist

Triamcinolone Acetonide (Azmacort)- Corticosteroid for asthma

EMULSION
Dispersion in which the dispersed phase is composed of small globules of a liquid
distributed throughout the vehicle in which it is immiscible (2-phased system)
Phases of Emulsion:
Internal- Discontinuous or dispersed phase
External- Continuous or dispersing medium, Larger amount
Emulsifying agent
Types of Emulsion:
O/W
W/O
Multiple emulsion (O/W/O or W/O/W)
Micro-emulsion
Most stable
Isotropic mixtures of a biphasic oil-water system stabilized by surfactants
Theories of Emulsification:
Surface Tension Theory
- Exposed surface of liquid tends to contract
- Internal forces in a liquid drop promote the association of the molecule of the
substance resisting distortion of the drop into a les spherical form
- Emulsifiers & stabilizers
- Lower the interfacial tension and reducing the repellant force between the
liquids
- Surfactants
- Facilitate the breaking up of larger molecules into smaller ones, having less
the tendency to coalesce
Oriented-Wedge Theory
- Emulsifying agents orient themselves about and within a liquid according to their
solubility in that liquid
- Emulsifying agent with greater hydrophilic character promotes an O/W emulsion
W/O emulsion through use of more hydrophobic emulsifiers

Plastic or Internal Film Theory

- Emulsifying agent: surrounds the droplets of the internal phase as a thin layer of
film absorbed on the surface of the drops
- Film: prevents the contact and the coalescence of the dispersed phase

Viscosity Theory
- Viscosity of an emulsion aids emulsification by the mechanical hindrance to
coalescence of the globules

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EMULSIFYING AGENT
Lowers the interfacial tension & forms a film at the interphase
Natural
- Carbohydrates: acacia (most frequently use), tragacanth & agar (thickening
agent), chondrus, pectin
- Form hydrophilic colloids with water and produce O/W emulsions
- Proteins: gelatin, egg yolk, casein
- Produce O/W emulsions
Synthetic
-Anionic: H2SO4 esters, sulfonic acid derivatives (dioctyl sodium sulfosuccinate) ,
soaps, triethanolamine oleate
- Cationic: used as surface-active agents in 1% conc; are incompatible with soaps
(benzalkonium chloride)
- Nonionic: sorbitan esters (span), polyethylene glycol 400 monostearate,
polyoxyethylene sorbitan esters (tweens)
- Finely divided solids: Ex: colloidal clays (bentonite, magnesium hydroxide and
aluminum hydroxide); Form O/W emulsions when the insoluble material is added to
the aqueous phase
- High molecular weight alcohols: Ex: stearyl alcohol, cetyl alcohol, glyceryl
monostearate ; Thickening and stabilizing agents for O/W emulsions (lotions &
ointments)
Emulsifying agent has:
Hydrophilic portion (water-loving)
Lipophilic portion (oil-loving)
HLB value (1-20) for each agent- indicates the substance polarity
* High polar (hydrophilic)
* Less polar (lipophilic)

Surfactants with
HLB value- 3 to 6 are greatly lipophilic; produce W/O emulsions
HLB value- 8 to 18 produce O/W emulsions
Selection of an emulsifier for an emulsion- same/ nearly the same HLB value
as the oleaginous phase

METHODS FOR PREPARING EMULSIONS:

English/ Wet Gum Method
Primary emulsion of fixed oil, water and acacia (4:2:1)
Make a mucilage (acacia + water) then add oil slowly
Continental/ Dry Gum method
Primary emulsion fixed oil, water and acacia (4:2:1)
Oil is added to acacia (uniformly distributed) then water is added all at once
Electrolytes at high conc tend to crack an emulsion
Alcoholic soln tend to dehydrate & ppt hydrocolloids
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Forbes/ Bottle Method
Variation of dry gum method for volatile oil, oleaginous substance of low viscosity
Oil added to acacia in a bottle (OWE, 3:2:1 or 2:1:1)
Nascent soap or In situ soap Method
Soap is formed (oil + aq soln with alkali)
O/W or W/O emulsion depending on the soap formed (olive oilw/ oleic acid &
Ca(OH)2 are mixed during the prep of calamine lotion

PROBLEMS ENCOUNTERED IN EMULSION:

Flocculation
Joining together of globules to form large lumps/ floccules rising and settling more
rapidly than the individual particles
Creaming
Rising/upward creaming (density of the internal phase is less than the external
phase)
Settling/ downward creaming (density of the internal phase is greater than the
external phase) of globules/ floccules forming a concentrated layer at the surface/
to the bottom
Globules are surrounded by a protective coating/ sheath of emulsifying agent and
re-dispersed by agitating the product
Coalescence and breaking
Irreversible processes
Coalescence of globules of internal phase and subsequent breaking/ cracking
(separation of layers) of emulsion
Freezing, thawing and high temperature result in the coarseness and breaking of an
emulsion
Methods for identifying emulsions:
Dilution method
Add water: W/O forms another phase, O/W homogenous
Dye solubility test
Amaranth green (water sol dye): O/W homogenous
Sudan red (oil sol dye): W/O homogenous
Conductivity test
O/W conducts electricity
Fluorescence test
Uses of UV light
Oil has property to absorb UV light, (+) for W/O

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