Ippp-Ii (SSDF)

Integrated Physical Pharmacy and Pharmaceutics II
SEMISOLID DOSAGE FORMS
Dereje K (PhD)
School of Pharmacy. Jimma University
Semisolid DF
Content
 Introduction
 Classification of semisolids
 Desired properties of semisolids
 Ointments and Pastes
 Creams
 Gels
Semisolid DF
Objectives
After completing this chapter, the student will be able to:
Differentiate between the various types of semisolid

bases on the basis of physical and chemical properties
List the criteria for the selection of a semisolid base to

treat a topical affliction
Describe the methods to incorporate (an) active

ingredient(s) into a semisolid base
Explain the difference between an ointment, a cream,

and a gel
Semisolid DF
Introduction
 Semisolid preparations
DF that have properties in between solid and liquid DF
Possess characteristic rheological properties
they can be easily applied on biological
membranes
 can be retained on the site of application for a
prolonged time
May contain one or more API in suspended/dissolved
forms state
Semisolid DF
Introduction…
 Applied topically to the skin or on the surface of the eye,
nasally, vaginally, or rectally for local and/or systemic
effects
Semisolid DF
Introduction…
 Most of these preparations are used for the effects of the
therapeutic agents they contain (medicated).
To exert local and systemic effects
Topical dermatological product is designed to deliver drug
into the skin in treating dermal disorders
Transdermal product is designed to deliver drugs through
the skin (percutaneous absorption) to the general
circulation for systemic effects
 The unmediated ones are used for their physical effects

as protectants or lubricants.
Semisolid DF
Classification of semisolids
Semisolid DF
Ideal Properties Of Semisolid DF
 Physical Properties:
Smooth texture
Elegant in appearance
Non dehydrating
Non gritty
Non greasy and non staining
Non hygroscopic
Semisolid DF
Ideal Properties Of Semisolid DF…
 Physiological Properties:
Non irritating
Do not alter membrane / skin functioning
Miscible with skin secretion
Have low sensitization index
Semisolid DF
OINTMENTS AND PASTES
Semisolid DF
Introduction
 Ointments are semisolid preparations intended for

external application to:
the skin
mucous membranes
 Ointments may be:

Medicated
Unmedicated ointments
 Non-medicated ointments are used for the physical

effects they provide as protectants, emollients, or
lubricants
Semisolid DF
Ointment Bases
 Non-medicated type being commonly referred to as

ointment bases.
 The ointment bases are used as:

emollients or lubricating agents
vehicles in the preparation of medicated ointments
Semisolid DF
Ointment Bases
 Ointment bases are generally classified by the USP into

four groups:
1. Hydrocarbon (oleaginous) bases
2. Absorption bases
3. water-removable bases
4. water-soluble bases.
Semisolid DF
Hydrocarbon (oleaginous) bases
 Have an emollient effect, and protect against the escape
of moisture,
 effective as occlusive dressings
 can remain on the skin for long periods without drying
out
Due to their immiscibility with water,

difficult to wash off
Small amount of water ( 5%) can be incorporated into
it with difficulty
Semisolid DF
Hydrocarbon (oleaginous) bases…
 Examples of HC bases
1. Petrolatum, USP
Yellow petrolatum/petrolatum jelly /Vaseline
Melts at 38-60oC
2. White petrolatum, USP

Decolored petrolatum, bleached and purified yellow wax)
White petroleum jelly/white Vaseline
Semisolid DF
3. Yellow ointment, USP

Yellow beeswax (5% w/w) + petrolatum (95% w/w )
4. White ointment, USP

White beeswax + white petrolatum
o Hydrocarbon bases frequently contain the following

components:
hard paraffin;
white/yellow soft paraffin; and
liquid paraffin (mineral oil)
Semisolid DF
1. Hard paraffin
A mixture of solid saturated hydrocarbons that are

derived from petroleum oil.
a colorless or white wax-like material that is physically

composed of a mixture of microcrystal.
The melting temperature of hard paraffin is between

47 and 65oc
used to enhance the rheological properties of ointment

bases.
Semisolid DF
2. White/yellow soft paraffin
 A purified mixture of semisolid hydrocarbons that are

derived from petroleum.
 The melting range of the soft paraffins is between 38 and

60oc.
Semisolid DF
3. Liquid paraffin (mineral oil, Liquid petrolatum)
 mixture of refined liquid saturated hydrocarbons obtained

from petroleum
 Levigating agent to incorporate lipophilic solids
 An excipient in topical formulations where its emollient

properties are exploited
Semisolid DF
 usually formulated with white/yellow soft paraffin to

achieve the required consistency
 Formulations containing liquid paraffin require the

incorporation of an antioxidant
due to the ability of this material to undergo oxidation.
Semisolid DF
Absorption bases
 are hydrophilic and, therefore, can absorb considerable

amounts of water or aqueous solutions
`1. Non-emulsified bases

These bases absorb water and aqueous solutions to
produce water-in- oil ( W/O ) emulsions
permit the incorporation of aqueous solutions resulting

in the formation of water-in-oil (W/O) emulsions
Semisolid DF
Absorption bases…
 Examples:
Hydrophilic petrolatum, USP
 (3% cholesterol in white petrolatum)
Anhydrous lanolin
wool alcohols
beeswax (white or yellow).
Aquaphor
 6 parts wool-wax alcohols and 99 parts of aliphatic hydrocarbons)
Semisolid DF
Absorption bases…
Lanolin (wool fat)

 Lanolin is a wax-like material that is derived from sheep’s wool.
 It is available in two forms, termed
Anhydrous lanolin (wool fat) and hydrous lanolin.
 Anhydrous lanolin:
 called wool wax, wool fat, or wool grease,
 a greasy yellow substance
 contains < 0.25% of water
Semisolid DF
Absorption bases…
 Typically mixed with paraffins to produce an ointment base
 Can absorb approximately twice its own weight of water to

produce water in oil emulsions.
 The usual concentrations of lanolin used in ointments (e.g.

Simple Ointment BP) range from 5 to 10% w/w.
Semisolid DF
Absorption bases…
 Wool fat is a major constituent of Simple Ointment B.P

and Eye Ointment B.P
Simple ointment B.P Eye Ointment B.P
Hard paraffin ………50g Liquid paraffin…..100g

Cetosteryl alcohol….50g Wool fat…………100g
Wool fat……………..50g Yellow soft paraffin……850g
Soft paraffin……….850g
Semisolid DF
Absorption bases…
Wool alcohols
 A crude mixture of sterols and triterpene alcohols
 Added to mixtures of paraffins (hard, so white/yellow soft

or liquid) to produce the required consistency.
 The inclusion of wool alcohols (5% w/w) results in a

300% increase in the concentration of water
eg. wool alcohol ointment B.P
Semisolid DF
Absorption bases…
Beeswax(white or yellow)
 A wax that consists of esters of aliphatic alcohols (C24–

C36) and linear aliphatic fatty acids (up to C36) that is
combined with paraffins to produce non-emulsified bases.
 White beeswax is the bleached form of yellow beeswax.
 included in some ointment bases to increase water-

absorbing power.
Semisolid DF
Absorption bases…
2. Water in oil emulsions (emulsion bases)

permit the incorporation of additional quantities of
aqueous solutions
similar in properties to the previous group and are
capable of absorbing water.
Absorption bases are less occlusive than the
hydrocarbon bases and easier to spread.
They are good emollients.
Eg. hydrous lanolin, which is a mixture of lanolin and
25–30% water.
Semisolid DF
Absorption bases…
 It is used alone as an emollient and is an ingredient of

several B.P.C ointment bases, i,e
Hydrous wool fat ointment
Calamine and coal tar ointment
Methylsalicylate ointment
Semisolid DF
Absorption bases…
Properties of absorption bases
 Non-emulsified absorption bases (anhydrous)

Emollient
Occlusive
Absorbs water
Greasy
 W/O emulsion
Emollient
Occlusive
Contains water, absorbs additional water
Greasy
Semisolid DF
Water-washable/removable bases
 Water-miscible bases that are used to form O/W
emulsions.
 They can be applied to scalp and other hairy regions.
 There are 3 official anhydrous water-miscible bases.

Emulsifying ointment B.P – anionic
Cetrimide emulsifying ointment B.P – cationic
Cetomacrogol emulsifying B.P- non-ionic
Semisolid DF
Advantages of water-miscible bases
able to accommodate large volumes of water
able to accommodate excess moisture
 e.g. exudate from abrasions & wounds.
Reduced interference with skin function
easily washed from the skin and from clothing.
readily applied to (and removed from) hair, skin.
High cosmetic acceptability
Semisolid DF
Characteristics of water removable bases

 Resemble creams in their appearance
 May be diluted with water or with aqueous solution
 Water washable
 Contains water
 Can absorb water
 Non-occlusive
 Non-greasy
Semisolid DF
Water-soluble bases
 They are completely water washable and often referred to

as greaseless.
 Developed from the Macrogols (Polyethylene glycols), a

range of compounds with the general formula:
H(OCH2CH2)nOH
 n represents the average number of oxyethylene
groups
Semisolid DF
Water-soluble bases…
 Polyethylene glycols are polymers of ethylene oxide and

water
Polycondensation
C 2H 4O + H 2O Poyethylene glycol
(Macrogol )
 The chain length may be varied to achieve polymers having desired
viscosity and physical form.
Macrogols 200,300 ,400 - Viscous liquids

Macrogols 1500 - Semi-solid
Macrogols 6000 - waxy solids
Semisolid DF
 Example
PEG ointment, NF
PEG 3350 ………400 g
PEG 400 ………. 600 g
Semisolid DF
Advantages of water- soluble bases

Water solubility
Easily removal from the skin
Readily miscible with tissue exudates
Good absorption by the skin
valuable when drugs are required to penetrate the skin
Good solvent properties
For some water soluble dermatological e.g. Hydrocortisone
Semisolid DF
Freedom from greasiness
Satisfactory ageing properties
 They don’t hydrolyze, rancidity or support microbial

growth
Compatibility with many dermatological medicaments
Semisolid DF
Disadvantages of water-soluble bases
Less bland than paraffins, possibly due to their

hygroscopic nature.
 Reduction in activity of certain antimicrobial agents, due

to hydrolysis
Solvent action on polythene and bakelite; these plastics

should not be used in containers or closures for macrogol
ointments
Semisolid DF
Summary of ointment bases
Properties Oleaginous Absorption Water-washable Water soluble

bases bases bases bases
Solubility in Insoluble in Insoluble in Insoluble in Soluble in water
water water water water
Washability Not water Not water water washable Water washable
washable washable
Absorption Not absorb absorbs absorbs water Absorbs water
of water water water To the pt of
solubility
Examples Hard paraffin, Wool fat, Cold creams, Macrogols

soft paraffin, wool alcohol, Emollient creams Liq. PEG 200
liq. paraffin lanolin, bees Hydrophilic Liq. PEG 200
wax ointment
Semisolid DF
Miscellaneous excipients
 Other excipients may be included in ointments and

pastes, including:
additional/alternative solvents
preservatives
antioxidants
Semisolid DF
Miscellaneous excipients…
Additional/alternative solvents
 are hydrophobic liquid components that may be added to

ointment bases (predominantly hydrophobic or absorption
bases).
 Examples of these include:

liquid silicone;
vegetable oils; and
organic esters
Semisolid DF
Liquid silicone (polydimethylsiloxane)

used in barrier ointments (water-repellent properties )
to protect the skin against water-soluble irritants
Vegetable oils
used to replace mineral oils
added to hydrophobic or absorption bases to increase
the emollient properties
Prone to oxidation requiring the inclusion of
antioxidants
stabilizers which may cause sensitization in some patients.
Semisolid DF
Organic esters
used to replace a mineral oil to enhance the
spreadability
to enhance drug dissolution within the ointment base.
Eg. isopropyl myristate (most commonly used)
Semisolid DF
Antioxidants
 employed to prevent or reduce oxidation of either the

non-aqueous components of the ointment base (e.g.
mineral/vegetable oils) and/or the therapeutic agent.
 lipophilic antioxidants
butylated hydroxyanisole (0.005–0.02%),
butylated hydroxytoluene (0.007–0.1%),
propyl gallate (<1%)
Semisolid DF
 Hydrophilic antioxidants
Sodium metabisulphate (0.01–0.1%),
Sodium sulphite (0.1%).
Semisolid DF
Preservatives
if the product contains water, then a preservative will be

required.
Preservatives that may be used in formulations designed

for external use include:
phenolics: phenol (0.2–0.5%), chlorocresol (0.075–0.12%)
benzoic acid and salts (0.1–0.3%)
methylparabens (methylparahydroxybenzoic acid)(0.02–0.3%)
propylparabens (methylparahydroxybenzoic acid) (0.02–0.3%)
benzyl alcohol ( 3.0%)
Semisolid DF
Selection of the Appropriate Base
 Factors that to be considered

Desired release rate of the drug substance from the
ointment base
Desirability of topical or percutaneous drug absorption
Desirability of occlusion of moisture from the skin
Stability of the drug in the ointment base
Semisolid DF
Selection of the Appropriate Base…
Effect, if any, of the drug on the consistency or other

features of the ointment base
Desire for a base easily removed by washing with water
Characteristics of the surface to which it is applied
Semisolid DF
Ideal Properties of an Ointment Base
Nonirritating, non-dehydrating, and non-greasy
Compatible with common medicaments
Stable
Easily removable with water
Good absorptive properties (water and other aqueous

liquids)
Good release properties of the drug from the base
Semisolid DF
Method of preparation
 A well-made ointment is:-

a). Uniform throughout, i.e. it contains
no lumps of separated high melting pt
ingredient of the base.
b). Free from grittiness, insoluble powders
are finely subdivided and large clumps of
particles are absent.
 Methods of preparation must try to satisfy these
criteria.
Semisolid DF
Method of preparation…
 Both an a large and a small scale, ointments are

prepared by two general methods.
 Incorporation
 Fusion
 The method for particular preparation depends primarily

up on the nature of ingredients.
Semisolid DF
1. Incorporation method
the component of the ointment are mixed together by

various means until a uniform preparation has been
attained.
Before incorporation the ingredient should have the finest

state.
Semisolid DF
Incorporation method
 On a small scale, as in the extemporaneous cpding of Rx:

Mortal and pestle
Ointment tile (Slab) and spatula
are a large glass or porcelain plate may be used to rub the
ingredients together.
Semisolid DF
Incorporation method …
 Mortar and Pestle
 Used:
when large quantities of liquids
are to be incorporated
when large quantity of ointment
is to be prepared
Otherwise, tile and spatula is
satisfactory due to its large
surface area
Semisolid DF
 Others instrument to prepare ointment in small scale
Electronic mortar and pestle An ointment mill ‘Unguator,”
Semisolid DF
 On a large scale
in stainless steel tank
Semisolid DF
A. Incorporation of solids
 When preparing an ointment by spatulation

stainless steel spatula with a long, broad blade
To periodically removes the accumulation of ointment on the
larger spatula with a smaller spatula.
 If the component of an ointment are reactive with the

metal of the spatula (eg, phenol), hard rubber spatula
may be used.
Semisolid DF
 The ointment is prepared by thoroughly rubbing and

working the component together on the hard surface with
the spatula until the product is smooth and uniform.
 Generally the ointment base is placed on one side of the

working surface, and the powdered components,
previously reduced to fine powders and thoroughly
blended in the mortar, area placed on the other
Semisolid DF
Then a portion of powder is mixed with a portion of the

base until uniform, and the process is repeated until all
portions of the powder and base are combined.
The portions of prepared ointment are then combined and

thoroughly blended by continuous & movement of the
spatula and through the combined portions of ointment.
Semisolid DF
 When only a small portion of powder is to be added, it

may be added in its entirely to a small portion of
ointment base.
 If the quantity of active ingredient is very small you

have to use levigating agent (mineral oil, and glycerin)
 After levigation, the dispersion is incorporated with the

remainder of the base by spatulation or by using the
mortar and pestle
Semisolid DF
B. Incorporation of liquids
Any liquids ingredients should be incorporated at the end

of levigation.
Generally, mortar and pestle is preferred when large

volumes of liquid are added than an ointment slab.
Semisolid DF
Fusion Method
 All or some of the components of an ointment are

combined by being melted together and cooled with
constant stirring until congested
 When ointment base contains several ingredients of

different melting point; first add constituent of high melting
point and then adding in descending order of meting
point.
Semisolid DF
Fusion Method
 Advantages of melting in descending order of melting

point:
Quicker
Require less heat
Avoid over heating or easily melted constituent
Semisolid DF
Fusion Method…
 Many substances are added to the congealing mixture in

solution
 others are added as insoluble powders generally

levigated with a portion of the base
 On a small scale; the fusion process may be conducted

in a porcelain dish or glass beaker
Semisolid DF
Fusion Method…
 On a large scale; it is generally carried out in large

steam-jacketed kittles
Semisolid DF
Fusion Method…
 Once congealed, the ointment may be passed through:

an ointment mill (in large-scale manufacture)
rubbed with a spatula or in a mortar (in small scale
ppn) to ensure a uniform texture.
Semisolid DF
Fusion Method…
 Many medicated ointments and ointment bases

containing such components, which do not tend
themselves well to mixture by incorporation, are prepared
by fusion
 For example
Beeswax
hard paraffin
stearyl alcohol,
high molecular weight polyethylene glycols,.
Semisolid DF
Fusion Method…
After melting; the melted ointment base should be stirred

taking care, not to cause localized cooling of high melting
ointment constituents .
Localized cooling can be occurred due to:-

Cold spatula or stirrer
Putting the dish on cold surface
Transferring melted base to cold dish
Semisolid DF
Fusion Method…
 If the product is granular after cooling, it has to be

remelted with minimum amount of heat and stirred gently
until it sets fully.
 We use fusion method when:

Constituents are with hard consistency
 High melting point components
The medicaments is soluble in melted base.
Semisolid DF
Difficulties encountered in ointment preparation
 Danger of chemical reaction between steel spatula and

some reactive ingredients.
Ex. I2 , salicylic acid, Benzoic acid………
 Solution:- to minimize this problem, use bone spatula,

wooden spatula or hard rubber spatula.
Semisolid DF
Difficulties encountered in ointment preparation…
 Incorporation of aqueous solution in to hydrocarbon base.
 Solution: addition of wool fat.
 Incorporation of antibiotics sensitive to hydrolysis
 Solution:- use hydrocarbon base.
Semisolid DF
Packaging and storage of ointment
 Ointments are usually packaged

either:
Jars
Tubes
 Jars
May be made of glass, uncolored,
dark green, amber, or blue
Or made of plastic, or porcelain
Tubes:- are made of tin or of plastic

(collapsible tube)
Semisolid DF
 Filling of the ointment into jars (small scale)

by means of a flexible spatula and forcing the
ointment down and along the sides of the jar to avoid
the entrapment of air
Ointments prepared by fusion may be poured directly

in to the ointment jars for congealing with in the ja
Semisolid DF
 In the large-scale manufacture of

ointments, pressure fillers force a
specified amount of an ointment in
to a jar.
 Tubes are generally filled by

pressure fillers from the open back
and (opposite and from the cap
end) of the tube which is then
closed and sealed.
Semisolid DF
 Tube-filled ointment predominate over jar-filled ointments

primarily b/s:
more convenient for the patient.
less exposed to air and to potential contaminants
likely to be more stable
 Most ointments must be stored at temperature below 300c

 to prevent the softening and liquefying.
Semisolid DF
PASTES
 Pastes, like ointments, are intended for external application to

the skin.
 They differ from ointments primarily in that they containing

large proportion of solid materials
 as a consequence are thicker and stiffer than ointment.
Semisolid DF
PASTES…
 Pastes are used principally as
 absorbents,
 antiseptics
 protective, or to soothe broken skin surfaces
Semisolid DF
PASTES…
 They are emollient but, because of the powder content, porous,

hence, perspiration can escape.
 The powder absorb exudates, less macerating than ointments

with similar base.
 Are less greasy than ointments because of the absorption of the

fluid hydrocarbon fraction to the insoluble particles.
Semisolid DF
PASTES…
 Most are unsuitable for treating scalp conditions because they

are difficult to remove from the hair.
 Because of the stiffness and absorptive qualities of pastes, they

remain in place after application with little tendency to softer
and flow
 therefore effectively employed to absorb secretion from the site
of application.
Semisolid DF
PASTES…
 Pastes are therefore preferred for acute lesions that have a

tendency toward crusting, or oozing.
 The film formed on application is opaque and thus can often

serve as a sun-block.
 Pastes are prepared similarly to ointments.
 However, when a levigating agents is to be used to render the
powdered component smooth, a portion of the base is often used

rather than a liquid like mineral oil
Semisolid DF
Creams
 Viscous emulsion or semi-solid emulsion preparation

consisting of solutions or dispersions of one or more
medicaments in suitable base
 intended for application to the skin or mucous membrane.
 widely used in pharmaceutical and cosmetic industry.
Semisolid DF
Creams….
 Many patients and physicians prefer creams to ointments.

they are generally easier to spread, and, in the case
of cream of the oil-in-water emulsion.
Easier to remove than many ointments
They are applied to the skin for:-

Protective
Beatifying
Therapeutic or prophylactic purposes
Semisolid DF
Creams…
 Creams may contain suitable antimicrobial or

preservatives unless the medicaments or basis have
sufficient intrinsic bactericidal and fungicidal activity
 Creams are mainly two types:

Water- in –oil (W/O) - oily cream
Oil –in-water (O/W) - aqueous cream
 O/W emulsions are most useful as water-washable

bases, whereas w/o emulsions are emollient and
cleansing
Semisolid DF
Creams…
 Patients often prefer O/W b/s

Cream spreads more readily.
Is less greasy
Evaporating water soothes the inflamed

tissue.
Semisolid DF
Creams
 O/W (varnishing cream)
 After application of the cream, the water evaporates

leaving behind a thin residue film of the stearic acid.
 For oozing or weeping surface (wound that release

exudates from skin) = b/s O/W mix oozing surface.
 Vanishing cream is prepared by incorporation of

significant amount of stearic acid in an oil-in-water
emulsion.
Semisolid DF
Creams
 Sodium or potassium hydroxide reacts with the stearic acid to

form a soap emulsifier.
 Humectants (glycerin, PEG, 7% sorbitol) are frequently added

to vanishing creams and O/W emulsions to decrease evaporation
of water from the surface of the base.
Semisolid DF
Creams
 Cold cream (W/O)

are useful as softening and cleansing agents
the cooling sensation associated with the slow

evaporation of the dispersed aqueous phase
Semisolid DF
General method of preparation for creams
 Prepared by heating the components of the oily phase

(usually including the emergent) until molten and then
cooling to 600c .
 The component of the aqueous phase are mixed in a

separate vessel and also heated to 600c.
 The aqueous phase is then added to the oily phase at the

same temperature.
Semisolid DF
 This is important and a thermometer should be used.

 The resulting emulsion should be stirred until cool .
 Rapid cooling may result in separation of high melting point

components.
 Excessive aeration caused by vigorous stirring may also lead to

a granular product.
Semisolid DF
 The active pharmaceutical ingredients (APIs) can be

added to the phase in which it is soluble at the
beginning of the process, or
 it can be added after the cream is prepared by a

suitable dispersion process such as levigation or milling
with a roller mill
Semisolid DF
Containers of Creams
 Wide-mounthed squat jars
used for creams where the risk of contamination in use is

considered to be minimal, e.g. Oils creams.
The container must be well closed and prevent water

evaporation.
The mouth of the jar should be covered with a disc of

grease proof paper.
Semisolid DF
Containers of Creams
 Collapsible metal or flexible plastic tubes

are to be preferred
since these reduce the risk of contamination in use and
most proprietary products are packed in tubes
Semisolid DF
Gels (gelies)
 Gels are transparent or translucent semi-solid or solid

preparations, consisting of solutions or dispersions of one
or more active ingredients in suitable hydrophilic or
hydrophobic bases.
Semisolid DF
Gels (gelies)…
 consisting of dispersions of small or large molecules in an

aqueous liquid vehicle by the addition of a gelling agent.
 Single-phase gels
gels in which the macromolecules are uniformly distributed
throughout a liquid with no apparent boundaries between
the dispersed macromolecules and the liquid.
Two-phase system
A gel mass consisting of floccules of small distinct particles
(often referred to as a magma)
Semisolid DF
Gels (gelies)…
 The dispersion medium:

Aqueous
Hydroalcoholic or oleaginous base
 Gels are attractive delivery systems:

simple to manufacture
suitable for administering drugs through skin, oral, buccal,
ophthalmic, nasal, otic, and vaginal routes
provide intimate contact between the drug and the site of
action or absorption.
Semisolid DF
Gels (gelies)…
Classification based on the chemical nature
1. Inorganic hydrogels
usually two phase systems such as aluminum
hydroxide gel
2. Organic Gels
usually single phase systems
may include such gelling agents as Carbomer and
Tragacanth and those that contain an organic liquid,
such Plastibase.
Semisolid DF
Gels (gelies)…
 Gels are also classified based on the physical properties

of the gelling agent in the dispersion
1. Hydrogels
prepared with water -soluble materials or water -

dispersible colloids
Natural and synthetic gums such as tragacanth, sodium alginate,
and pectin
inorganic materials: alumina, bentonite, silica, and veegum
organic materials such as cellulose polymers
Semisolid DF
Gels (gelies)…
2. Organogels (oleaginous gels)
prepared using water - insoluble oleaginous materials/

lipids such as glycerol esters of fatty acids, which swell in
water
Eg. Glycerol monooleate, glycerol monopalmito stearete, and
glycerol monolinoleate
Allows incorporation of both hydrophilic and lipophilic

drugs
Semisolid DF
Components in gel formulation
1. Gelling agent
 Gelling agent causes thickening
 are either organic hydrocolloids or hydrophilic inorganic

substance.
 They are water dispersible, possess swelling properties,

and improve the viscosity of dispersions
Semisolid DF
Components in gel formulation…
1. Acacia 13. Ethylcellulose

2. Bentonite
15. Guar gum
3. Carboxymethylcellulose Na
16. Hydroxypropryl cellulose
4. Colloidal silicon dioxid
17. Magnesium Al silicate
5. Gelatin
6. Hydroxyethylcellulose 18. Methylcellulose
7.Hydroxyproprylmethylcelluose 19. Povidone
8. Maltodextrin 20. Sodium alginate
9. Polyvinyl alcohol 21. Sodium starch glycolate
10. Propylene carbonate 22. Starch
11. Alginic acid
23. Tragacanth
12. Carbomer
24. Xanthan gum
13. Cetostearyl Alcohol
Semisolid DF
2. Preservatives
 Methylhydroxybenzoate
 Propylhydroxybenzoate
3. Hygroscopic agents ( Humectant)
 To prevent skin formation.
Eg. Glycerol, propylene glycol or sorbitol solution.
4. Chelating agents
 For ingredients which are sensitive to heavy metals. eg.
EDTA.
Semisolid DF
6. Flavours/sweetening agents
 Included in pharmaceutical gels that are designed for

administration into the oral cavity
e.g. for the treatment of infection, inflammation or ulceration.
7.Buffers
 As in other pharmaceutical formulations, buffers (e.g. phosphate,

citrate) may be included in aqueous & hydroalcoholic-based gels
Semisolid DF
Preparation of Gels
 Generally, the water soluble components are initially dissolved

in the vehicle in a mixing vessel with stirring.
 The hydrophilic polymer must be added to the stirred mixture

slowly to prevent aggregation then continuing stirring until
dissolution of the polymer
 excessive stirring of pharmaceutical gels results in
entrapment of air.
 Therefore, to prevent this the mixing rate must not be excessive

Semisolid DF
Uses/application of Gels
 medication
 Lubrication
 miscellaneous applications
Patch testing : As a vehicle for allergens applied to the skin
to detect sensitivity
as carriers for spermicidal agents to be used intravaginally
with diaphragms as an adjunctive means of contraception.
Semisolid DF
Containers for Gels
 Containers should be well-filled
 to minimize evaporation of water into the air space,
 well closed and stored in a cool place
 to prevent drying out
Avoid freezing gels.
Semisolid DF
Quality Control Tests for Ointments
1. Consistency
2. Spreadability test
3. Drug content
4. in vitro drug release
5. Rheological Properties
6. Microbial limit test
7. Particle size
Semisolid DF
Percutaneous absorption of a drug
Semisolid DF
Skin structure
Semisolid DF
Skin structure
 The largest organ of the body, it is thin at some places (eye lids
thickness =0.5 mm) where as thick at other places (sole of foot,

palm of hand thickness=5mm).
 Average thickness of skin is 1-2mm (0.04-0.08in).
 In adults, the skin covers an area of about 2 square
Semisolid DF
Skin structure
 Skin consists of three layers
Semisolid DF
Skin structure
Epidermis
 The superficial , thinner portion composed of keratinized
stratified squamous epithelial tissue
 it is nourished by diffusion of nutrients from a vascular network

of dermis
 Composed of 4 type of cells

1. keratinocytes 3. langerhans cell
2. melanocyets 4. merkel cell
Semisolid DF
Skin structure
keratinocytes
keratino= horny like, cytes=cell
 90 % of epidermal cells are keratinocytes.
 Responsible for production of keratin…a tough fibrous protein
 protect the skin and underlying tissues from heat, microbes

and chemical.
Semisolid DF
Skin structure
Melanocytes: Melano=black, cytes=cell
 8% of epidermal cells are melanocytes.
 Produces a pigment melanin (a yellow red or black brown

pigment) contribute:
 in skin color
 absorbs damaging u-v light
Semisolid DF
Skin structure
Langerhans cells
 Participate in immune responses against microbes that invade

the skin
 Helps other cells of immune system to recognize an invading

microbe and destroy it.
Merkel cell
 Participate in detection of touch sensation.
Semisolid DF
Skin structure
 Epidermis consists of different c) Stratum granulosum

layers (Granular layer)
a) Stratum corneum (Horney  Participate in keratinisation
layer) d) Stratum spinosum (Prickle
Barrier to Percutaneous cell layer)
absorption e) Stratum basale (Stratum
b) Stratum lucidum (Barrier germinativum)
zone)  Melanocytes the pigment-
producing cells of the epid
 Barrier to transfer of water
across skin,
 damage resulted in increased
permeability.
ermis
Semisolid DF
Skin structure
Semisolid DF
Skin structure
Dermis :
 The sensitive connective tissue layer of the skin located below

the epidermis, containing nerve endings, sweat and sebaceous
glands, and blood, hair follicles, fibroblast, histocytes and
lymph vessels.
 Composed of strong connective tissue containing collagen (for

strength) and elastin (for stretch )
 Play major role in temperature regulation.

Semisolid DF
Skin structure
Hypodermis :
 Below the dermis is hypodermis also k/as subcutaneous layer
Sub mean under and cutaneous mean skin.
 Loose layer of connective tissue which is anchored to the
underlined tissue ( muscle and bones).
 Most fat cells are present in hypodermis (adipose tissues)

 acts as insulator to protect the body from excessive heat
and cold environment
Semisolid DF
Skin structure
Skin appendages
1.Sweat glands
 The sweat glands are coiled tubules in the dermis which open on to
the skin surface; they can be sub-divided in to two classes;
 Eccrine glands:
 The sweat glands which are involved in the regulation of
body temperature by water elimination.
 About two million eccrine sweat glands on the average human
body. Semisolid DF
Skin structure
 Apocrine sweat glands:

 Are larger than eccrine sweat but few in number.
 They are mainly located in the hairier regions of the maxillae

and around the nipples.
 Apocrine sweat differs in composition from eccrine and may

be cloudy and colored
Semisolid DF
Skin structure
2.Hair follicles
 Hair follicles are sebum-filled openings from which keratinous

hair filaments protrude.
 Follicles occupy about 0.1% of the skin surface area; but are
absent from plantar and palmar surfaces, the red areas of the
lips, and parts of the genitalia.
Semisolid DF
Functions of skin
Containment of body fluid and tissue
Protection from external stimuli
 Microbial barrier
 Chemical barrier
 radiation barrier
 Thermal barrier
Semisolid DF
Percutaneous absorption
(Transdermal drug delivery)
The absorption of substances from outside the skin to positions

beneath the skin, including entrance into the blood stream
 Drugs may penetrate intact skin after topical application through
 the walls of the hair follicles,
 the sweat glands
 the sebaceous glands,
 Trough the cells of the horny layer
Semisolid DF
Percutaneous absorption …
 The main route for the penetration of drug is generally
through the epidermal layers ( b/c of surface area )
 The stratum corneum is the outermost ‘horny’ layer of
skin, comprising about partially desiccated, dead,
keratinized epidermal cells.
 It is the rate-limiting barrier to percutaneous drug transport
Semisolid DF
 Transport of lipophilic drug molecules is facilitated
 by their dissolution into intercellular lipids
 Absorption of hydrophilic molecules into skin can occur

through ‘pores’ or openings of the hair follicles and sebaceous
glands
 But, the relative surface area of these openings is barely 1% of

the total skin surface.
limits the amount of drug absorption

Semisolid DF
Semisolid DF
 Permeation of the substances in SC can occur by diffusion via:
1.Transcellular penetration
2. Intercellular penetration
Semisolid DF
Advantages of Transdermal Delivery
 Avoids the unpredictability associated with gastrointestinal

absorption
 No hepatic first pass effect and an improvement in

bioavailability.
 Noninvasive, thus no pain associated with administration.
 Desired plasma levels can be maintained over longer duration.
 Increases patient compliance.
 Reduces frequency of administration.
 Reduces side effects.

Semisolid DF
Factors influencing Percutaneous absorption
1. Skin conditions
Occluded and disease
Age
Blood flow
Site of the skin
Skin hydration
Temperature
Sex and race
Semisolid DF
Factors influencing Percutaneous absorption. ..
2. Physicochemical characteristics of the drug

Concentration of drug at the site of action
Molecular weight
Partition coefficient
Melting point
Semisolid DF
Factors influencing Percutaneous absorption. ..
3. Formulation Factors (Vehicle)

Partition coefficient
Degree of hydration
Viscosity of vehicle
Semisolid DF
Maximizing the bioavailability of drug to skin
 Drug or prodrug selection
 Hydration
 Ultrasounds(phonophoresis)
 Ionophoresis
 Stratum corneum removal
 Chemical penetration enhancers
Semisolid DF
CASE STUDIES
Mr. Abebe needs to purchase a

prescription of 0.25% (w/w) steroid cream
to treat eczema on his infant son’s
cheeks. He asks the pharmacist about a
prescription he got from her doctor two
weeks ago for the same steroid but at a
higher concentration and ointment(1%).
Since the cost of this topical formulation
is very high, she wants to know why he
needs to purchase the 0.25% cream for
his son when she could use the leftover
1% ointment instead. How should the
pharmacist respond to Mr. Abebe?
Semisolid DF
CASE STUDIES
 Can Mr Abebe use the leftover 1% ointment instead of

the prescribed one? why?
 If the 0.25% of the cream is not available on the market at

all, and only 1% cream exist, how do you help the
patient?
 If you decided to prepare 0,25% cream from 1% by

dilution with vanishing cream (cream base) to dispense
the total of 50g, how many gram of 1% and cream base
do you use?
Semisolid DF
Summary
 List the common semisolid DF
 Differences between ointment, paste, cream and gels
 Types of ointment bases with examples
 Method of preparation of ointment
 Instrument used to prepare ointment
 Container and storage of somisolid DF
Semisolid DF
Summary
 Advantages of transdermal drug delivery system
 Discuss the mechanism of drug penetration through the

skin
 Factor affecting TDDS
 Limitation of TDDS
 Explain the physical methods to enhance topical drug

delivery
Semisolid DF
Summary…
 Sulfur ointment, B.P

Precipitated Sulfur, finely sifted------100g
Simple ointment---------------------------900g
 Simple ointment BP
Wool fat-----------------------------------50g
Hard paraffin-----------------------------50g
Cetostearyl alcohol----------------------50g
Yellow or white soft paraffin---------850g
Semisolid DF
Summary….
Vanishing Creams
Purified water……………………………79g
Stearic acid………………………………15g
Potassium Hydroxide............................Q.S
Glycerin...................................................5g
Semisolid DF

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Integrated Physical Pharmacy and Pharmaceutics II

SEMISOLID DOSAGE FORMS

 Desired properties of semisolids

 Ointments and Pastes

Differentiate between the various types of semisolid

List the criteria for the selection of a semisolid base to

Describe the methods to incorporate (an) active

Explain the difference between an ointment, a cream,

 The unmediated ones are used for their physical effects

Non greasy and non staining

Do not alter membrane / skin functioning

Miscible with skin secretion

Have low sensitization index

 Ointments are semisolid preparations intended for

 Ointments may be:

 Non-medicated ointments are used for the physical

 Non-medicated type being commonly referred to as

 The ointment bases are used as:

 Ointment bases are generally classified by the USP into

1. Hydrocarbon (oleaginous) bases

Due to their immiscibility with water,

2. White petrolatum, USP

3. Yellow ointment, USP

4. White ointment, USP

o Hydrocarbon bases frequently contain the following

A mixture of solid saturated hydrocarbons that are

a colorless or white wax-like material that is physically

The melting temperature of hard paraffin is between

used to enhance the rheological properties of ointment

2. White/yellow soft paraffin

 A purified mixture of semisolid hydrocarbons that are

 The melting range of the soft paraffins is between 38 and

3. Liquid paraffin (mineral oil, Liquid petrolatum)

 mixture of refined liquid saturated hydrocarbons obtained

 Levigating agent to incorporate lipophilic solids

 An excipient in topical formulations where its emollient

 usually formulated with white/yellow soft paraffin to

 Formulations containing liquid paraffin require the

 are hydrophilic and, therefore, can absorb considerable

`1. Non-emulsified bases

permit the incorporation of aqueous solutions resulting

Lanolin (wool fat)

 Typically mixed with paraffins to produce an ointment base

 Can absorb approximately twice its own weight of water to

 The usual concentrations of lanolin used in ointments (e.g.

 Wool fat is a major constituent of Simple Ointment B.P

Simple ointment B.P Eye Ointment B.P

Hard paraffin ………50g Liquid paraffin…..100g

 A crude mixture of sterols and triterpene alcohols

 Added to mixtures of paraffins (hard, so white/yellow soft

 The inclusion of wool alcohols (5% w/w) results in a

eg. wool alcohol ointment B.P

 A wax that consists of esters of aliphatic alcohols (C24–

 White beeswax is the bleached form of yellow beeswax.

 included in some ointment bases to increase water-

2. Water in oil emulsions (emulsion bases)

 It is used alone as an emollient and is an ingredient of

Calamine and coal tar ointment

Properties of absorption bases

 Non-emulsified absorption bases (anhydrous)

 They can be applied to scalp and other hairy regions.

 There are 3 official anhydrous water-miscible bases.

Cetrimide emulsifying ointment B.P – cationic