Semisolids

Introduction
• Ointments, creams and gels are semisolid
dosage forms intended for topical application
(skin and mucus membrane).

• They may be applied to the skin, placed on the

surface of the eye, or used nasally, vaginally, or
rectally.

• Mostly used for the effects of the therapeutic

agent they contain. Un-medicated ones are used
for their physical effects as protectants,
emollients, or lubricants.
• Topical applications can be designed for either:
–Local effects.
–Systemic absorption.

• Topical dermatological product: Designed to

deliver drug into the skin in treating dermal
disorders, with the skin as the target organ.

• Transdermal product: designed to deliver drug

through the skin (percutaneous absorption) to
the general circulation for systemic effects, with
the skin not being the target organ.
 Ointments
 Ointments: semisolid preparations intended for
external application to the skin or mucous
membranes.
 Could be medicated or un-medicated.

 Ointment bases: according to the USP, they

are classified into:
1. Oleaginous bases
2. Absorption bases
3. Water-removable bases
4. Water-soluble bases
1. Oleaginous bases (hydrocarbon bases):

– On application on the skin, they have an emollient

effect and they protect against the escape of
moisture.
– They are effective as occlusive dressings as they
can remain on the skin for long periods of times
without drying out and they are immiscible with
water and are difficult to wash off.

 Examples: petrolatum, white petrolatum, white

ointment, and yellow ointment.

 Water and aqueous preparations may be incorporated,

but only in small amounts and with some difficulty.
Petrolatum, USP:
– It is a purified mixture of semisolid
hydrocarbons obtained from petroleum.
– It varies in color from yellowish to light amber.
– It melts at 36 – 60 C.
– Also known as yellow petrolatum or petroleum
jelly.
– Commercial product: Vaseline.
White Petrolatum, USP:
– It is a purified mixture of semisolid
hydrocarbons obtained from petroleum that
has been wholly or nearly decolorized.
– It is used for the same purpose as petrolatum.
Because of its light color, it is considered
more esthetically pleasing by some patients
and pharmacists.
– Also known as white petroleum jelly.
– Commercial product: white Vaseline.
 Yellow Ointment, USP:
– It has the following formula:
Yellow wax 50 g
Petrolatum 950 g

– Yellow wax is the purified wax obtained form the

honeycomb of the bee Apis mellifera.
– Also called simple ointment.
– It has a slightly greater viscosity than plain petrolatum
– It is prepared by
• Melting the yellow wax on a water bath
• Adding the petrolatum until the mixture is uniform
• Cooling and stirring until congealed.
White Ointment, USP:
– Differs from yellow ointment by substitution of
white wax (bleached yellow wax) and white
petrolatum in the formula.
2. Absorption bases:
 Two types:
 Those that permit the incorporation of aqueous
solutions resulting in the formation of w/o
emulsions (e.g., hydrophilic petrolatum)
 Those that are w/o emulsions (also known as
emulsion bases) that permit the incorporation of
additional quantities of aqueous solutions (e.g.,
lanolin)
 They are not easily removed from the skin with
water washing, since the external phase of the
emulsion is oleaginous
 They are useful for incorporation of small volumes
of aqueous solutions into hydrocarbon bases
 first, incorporate the aqueous solution into the
absorption base then, incorporate the mixture into
the hydrocarbon base.
W/O emulsion O/W emulsion

11
 Hydrophilic Petrolatum, USP:
– It has the following formula:
Cholesterol 30 g
Stearyl alcohol 30 g
White wax 80 g
White petrolatum 860 g

– It is prepared by:
• Melt the stearyl alcohol and white wax on a steam bath
• Add the cholesterol with stirring until dissolved
• Add the white petrolatum
• Allow the mixture to cool while stirring until congealed.

– Commercial product: Aquaphor  has the capacity to

absorb up to three times it weight in water
 Lanolin, USP:
– Obtained from the wool of sheep.
– It is a wax-like substance that has been
cleaned, deodorized and decolorized.
– It contains not more than 0.25% of water.
Additional water may be incorporated into
lanolin by mixing.
3. Water-removable bases:
– They are o/w emulsions
– Can be easily washed from the skin with
water (often called water washable bases).
– They may be diluted with water or aqueous
solutions.
– They can absorb serous discharges.
– Hydrophilic Ointment, USP, is an example of
this type of base.
 Hydrophilic ointment, USP:

– Formula (1000 g)
Methylparaben 0.25 g
Ethylparaben 0.15 g
Sodium lauryl sulfate 10 g
Propylene glycol 120 g
Stearyl alcohol 250 g
White petrolatum 250 g
Purified water 370

– Emulsifying agent : SLS

– Oleaginous phase: Stearyl alcohol & white petrolatum
– It is prepared by:
• The stearyl alcohol and white petrolatum are melted
together at about 75°C.
• The other agents, dissolved in the purified water, are
added with stirring until the mixture congeals
Sodium lauryl sulfate

Stearyl alcohol
4. Water-soluble bases
– They do not contain oleaginous
components.
– They are completely water washable and
often referred to as greaseless.
– They can not incorporate large amount of
aqueous solutions  they become very soft.
– They mostly are used for incorporation of
solid substances.

Example: Polyethylene glycol ointment, USP.

• Polyethylene glycol (PEG):
– It is a polymer of ethylene oxide and
represented by the following formula
H(OCH2CH2)nOH
PEG has numerical designations that refers to
the average molecular weight of the polymer.
– Depending on the average molecular weight:
–PEG < 600: clear colorless liquid
–600 < PEG < 1000: semisolid.
–PEG > 1000: wax-like white material
• The general formula for preparing 1000 g of polyethylene
glycol ointment, NF is:
PEG 3350 400 g
PEG 400 600 g

• Combining PEG 3350 (solid) with PEG 400 (liquid)

results in a pliable semisolid ointment.
• If a firmer ointment is desired, the formula may
be altered to contain up to equal parts of the two
ingredients.
 SELECTION OF THE APPROPRIATE
BASE
• Selection of the base to use in the formulation of an
ointment depends on careful assessment of a number of
factors, including the following:
– 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.
– 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
• For example:
– An ointment is generally applied to dry, scaly
skin.
– A cream is applied to weeping or oozing
surfaces
– A lotion is applied to intertriginous areas or
where friction may occur, as between the
thighs or under the armpit.

• The base which provides the best

combination of the most desired attributes
should be selected.
• Preparation of ointments:
– There are two general methods:
1. Incorporation
2. Fusion

1. Incorporation:
• The components are mixed until a uniform
preparation is obtained.
• In extemporaneous compounding (small scale): the
pharmacist often use a spatula to rub the
ingredients together on an ointment slab.
 Incorporation of solids:
– When preparing an ointment by spatulation  the
pharmacist works the ointment with a stainless
steel spatula having a long, broad blade.
– He would periodically removes the accumulation
of ointment on the large spatula with a smaller
one.
– A metal spatula is always used unless one of the
components reacts with metal (e.g., Iodine), then
a hard rubber spatula should be used.

x
• The ointment is prepared by thoroughly rubbing and
working the components together on the hard surface
until the product is smooth and uniform:
• Place all solid material in a mortar
• Grind and blend the solid powders thoroughly.
• Transfer the powder to one side of the ointment
slab.
• Place the ointment base on the other side of the
slab.
• Mix one portion of the powder with a portion of
the base until uniform
• Continue mixing in a geometric dilution fashion till
the powder and the ointment base in thoroughly
and uniformly blended.
Incorporation of solids:
– It often is desirable to reduce the particle size
of a powder or crystalline material before
incorporation into the ointment base so the
final product will not be gritty.
– How to achieve that?
• Trituration of large crystalline material using a
mortar and pestle
• Levigation.

– Levigation: mixing the solid material with a

vehicle in which it is insoluble to make smooth
dispersion (while wet)
 Levigating agent
• Mineral oil when for oleaginous bases.
• Glycerin for hydrophilic bases.
• Or a small portion of ointment/cream base
itself

– How much levigating agent? About equal

volume to the solid material.
– Where to levigate? In a mortar with a pestle or
directly on the ointment slab with a spatula.
– Advantages: reduction of particle size +
dispersion of the powder.
• Consider the following case:
– You have solids (could be the drug or some additives)
that you want to incorporate in the ointment/cream
where:
• They are soluble in a common solvent.
• The solvent will affect neither the stability of the drug
nor the efficacy of the product.
– To incorporate such solids,
• You may first dissolve them in that solvent (e.g.,
water or alcohol).
• The solution is added to the ointment base by
spatulation or in a mortar and pestle.

• The mortar and pestle method is preferred when large

volumes of liquid are added, because the liquid is more
captive than on an ointment slab.
Incorporation of solids:
– For gummy materials such as or very hard materials
such as camphor and menthol :
– Place the crystals on the middle of the ointment
slab
– Add few drops of alcohol or isopropyl alcohol to
dissolve the crystals with a spatula.
– Spread the solution on the slab and allow it t
evaporate.
– Scrub the thin film from the slab with the
spatula and incorporate the powder material
into the ointment base.
• For the camphor and menthol case, you may
also do the following to incorporate them:
• Place both of the crystalline materials on
the middle of the ointment slab.
• Rub them against each other with pressure
using a metal spatula.
• This will form an eutectic mixture with a
melting point below room temperature 
crystals will melt and form a liquid oily
mixture on the slab.
• Incorporate this oily liquid with a portion of
the base and continue mixing till all the
liquid is absorbed by the base.
Incorporation of liquids:
– Can be added to the ointment after careful
consideration of the ointment base’s capacity to
accept the volume of liquid required.
– Aqueous solution may be incorporated into
hydrophobic bases (e.g., petrolatum) by using an
absorption base (e.g., aquaphor) or a hydrophilic
base (e.g., hydrophilic ointment, USP).
– Nevertheless, the capacity of hydrophilic bases are
limited and high quantity of liquid will result in an
ointment that is too soft or semi-liquid.
– Alcoholic solutions of small volume may be added
easily to oleaginous bases or emulsion bases.
 aqueous harder hydrophobic
preparation, only base, only oil
water

easier

absorption base
( W/O emulsions)
• Final note on the Incorporation method for the
preparation of ointment:
– Ointment or roller mills can be used to force
coarsely formed ointments through stainless
steel or ceramic rollers.
– This will produce ointments uniform in
composition and smooth in texture.

• Small ointment mills also find use in product

development laboratories and in small batch
manufacture or compounding.
2. Fusion method:
– All or some of the components of the ointment are
combined by being melted together then cooled with
continuous stirring until congealed.

– Components that are not melted are added to the

congealing mixture as it is being cooled and stirred.

– Heat-labile substances and volatile components

should be added last, when the temperature of the
mixture is low enough not to cause any
decomposition or volatilization of the components.
• How to prepare in on small scale? fusion may be
conducted in a porcelain dish or glass beaker.

• When to use the fusion method? When the ointment

base has components such as
– Beeswax
– Paraffin
– Stearyl alcohol
– High molecular weight PEG

• Why such substances? Because they don’t lend

themselves well to mixture by incorporation..
• Melting procedure:
A. The material with the highest melting points should
be heated to the lowest required temperature to
produce a melt
or
B. The materials with the lowest meting point is melted
first then, the remaining components are added in
order of their melting points (form low to high) under
slow increase of temperature  fusion of all
components is achieved at lower temperature than
would be expected for the highest melting point
component due to solvent action exerted by the first
melted components on the others.
C. For preparation of ointments having an emulsion base  the
method of manufacture involves both melting and
emulsification.
 The water-immiscible components such as the oil and
waxes are melted together in a steam bath (70 – 75
C).
 Meantime, an aqueous solution of the heat stable,
water soluble components is prepared and heated to
the same temperature as the oleaginous phase.
 Add the aqueous solution slowly with continuous stirring
to the melted oleaginous mixture.
 Maintain the temperature for 5-10 minutes then cool the
mixture with continuous stirring until congealed.

 Note: if the aqueous solution is not at the same

temperature as the oleaginous melt  some of the waxes
will solidify on addition of the colder aqueous solution to
the melted mixture.
 Creams
• They are semisolid preparation containing one or more
medicinal agents dispersed in either a w/o emulsion or
o/w emulsion or in any other type of water-washable
base.

• Creams are preferred over ointments because they are

easier to spread and remove.

• Pharmaceutical manufacturers frequently manufacture

topical preparations of a drug in both cream and
ointment bases to satisfy the preference of various
patients and physicians.
 PASTES

PASTES
• Pastes are semisolid preparations intended for
application to the skin. They generally contain a
larger proportion of solid material (such as 25%)
than ointments and therefore are stiffer.

• Pastes can be prepared in the same manner

as ointments, by direct mixing or the use of heat
to soften the base prior to incorporating the solids.
 PASTES

• Because of the stiffness of pastes, they remain

in place after application and are effectively
employed to absorb serous secretions.

• Because of their stiffness and impenetrability,

pastes are not suited for application to hairy
parts of the body.
 PASTES
• Among the few pastes in use today is zinc
oxide paste , which is prepared by mixing
25% each of zinc oxide and starch with
white petrolatum.

• The product is very firm and is better able

to protect the skin and absorb secretions
than is zinc oxide ointment.
 GELS

• Gels are semisolid systems consisting of

dispersions of small or large molecules in an
aqueous liquid vehicle rendered jellylike by the
addition of a gelling agent.

Among the gelling agents used are synthetic

macromolecules, such as carbomer 934;
cellulose derivatives, and natural gums, such as
tragacanth.
• Single-phase gels are gels in which the
macromolecules are uniformly distributed
throughout a liquid with no apparent
boundaries between the dispersed
macromolecules and the liquid.

• A gel mass consisting of floccules of small

distinct particles is termed a two-phase
system, often referred to as a magma.
• In addition to the gelling agent and water, gels
may be formulated to contain a drug substance,
solvents, such as alcohol and/or propylene
glycol;
antimicrobial preservatives, and stabilizers,
such as edetate disodium.
• Medicated gels may be prepared for
administration by various routes, including the
skin, the eye, the nose, the vagina, and the
rectum.
 Packaging and Storage
• Ointments as well as all other semisolid preparations are
packaged either in:
• Large-mouth ointment jars
• Metal or plastic tubes.

• Ointments should be stored in a closed containers to

prevent against microbial contamination.

• Ointments should be stored in a cool place to avoid

product separation by heat.
• Standard sizes of empty tubes have
capacities of 1.5, 2, 3.5, 5, 15, 30, 45, 60,
and 120 g.
• Topical preparations are usually frequently
packaged in 5, 15, and 30 g tubes.
• Ophthalmic ointments are
typically packaged in
3.5 g tubes.
• Filling ointments jars:
– On a small scale in the pharmacy, ointments
jars can be filled by carefully transferring the
weight amount of ointment into the jar with a
spatula.

– The jar size should be selected so that the

ointment reach near the top of the jar but not
so high as to touch the lid when closed.

– Ointments prepared by fusion may be poured

directly into the jar to congeal in it.
 Features and Use of
Dermatological Preparations
• The target organ is the skin
• The drug in a medicated application (e.g.,
ointment or cream) should penetrate or be
retained in the skin for a while.
• Drug penetration into the skin depends on a
number of factors, including
– The physicochemical properties of the drug.
– The characteristics of the pharmaceutical vehicle.
– The condition of the skin (broken versus unbroken)
• The skin is divided histologically into
– The stratum corneum (the outer layer, part of
the epidermis)
– The living epidermis
– The dermis

• All these layers form collectively a laminate of barriers

that protect against permeation by external compounds
and loss of water from the body.

• Blood capillaries and nerve fibers rise from the

subcutaneous fat into the dermis and up to the
epidermis.
• Sebaceous glands, sweat glands and hair
follicles originates in the dermis and
subcutaneous layer and rise to the skin surface.

• The stratum corneum is 10 – 15 m of flat,

partially desiccated, dead epidermal cells.

• The stratum corneum is composed of

40 % protein (mainly keratin)
40% water
20 % lipids: triglycerides, free fatty acids,
cholesterol and phospholipids.
• Hair follicles and gland ducts can provide
entry for drug molecules. But because
their relative surface area is so minute
compared to the total epidermis, they are
minor factors in drug absorption.

• The stratum corneum being a keratinized

tissue, behaves as a semi-permeable
membrane, and drug molecules can
penetrate by passive diffusion.
• The rate of drug movement across the stratum corneum
layer depends on:
– Drug concentration in the vehicle.
– The aqueous and lipid solubility of the drug
– The distribution coefficient of the drug between
the stratum corneum and the drug vehicle.

• Substances with both, water and lipid solubility

characteristics are good candidates for diffusion in the
stratum corneum.

• Once in the stratum corneum, they drug molecules may

pass through the deeper epidermal tissues and the
dermis layer.
• If the drug reaches the vascularized dermal
layer, it becomes available for absorption into
the general circulation.

• In transdermal delivery: the drug level in the

blood can be measured and equated against the
desired therapeutic effect.

• In topical dermatological product: the

therapeutically effective concentration of the
drug in the skin is unknown and can’t be
measured  the treatment therefore is based on
qualitative measures with clinical efficacy
varying between patients and products.
• The different types of bases vary in:
– Emollient and occlusive effects.
– Ease of application of the product
– Ease of removal of the product.

 Oleaginous bases: provide higher

emollient and occlusive effects.
 Creams (o/w emulsions): spread more
easily and easier to remove.
 Water-soluble bases: non greasy and
easily removed.