CHAPTER VI

MEDICATED APPLICATIONS
They are generally referred to as therapeutic ointments creams pastes
and other forms of viscous consistency intended for external application onto skin.
Use of Medicated Applications
1. As vehicles for topically applied drugs
2. As emollients provides soothing of softening effect on the surface tissues.
3. As protective or occlusive dressing on the skin.
Factors Influencing Absorption of Drugs Through Skin
I.
II.

III.
IV.

Participation Coefficient of the Drug Substance

Substances possessing both water and lipid solubility are favorably
absorbed through the skin.
Moisture and Temperature in the Environment of the Skin
The moisture balance in the stratum corneum layer of the epidermis
is due to the presence of a combination of compounds known as the
natural moisturizing factors. These compounds claims that the fat on the
human skin provides a protective film to prevent this factor from being
stripped from the skin during excessive contact with water as in bathing.
The skin constantly releases water in the skin surface, which
evaporate quickly without being noticed. This is called insensible
perspiration. When the environment has a high moisture content the rate
of evaporation is slowed down and rthe person becomes aware of the
clammy moist sensation on his skin. There are drug substance which
penetrate faster, when the temperature of the environment is higher one
example as aspirin.
Pathological Injury to the Skin
Skin penetration has been enhance by abrasions or whn the skin is
stripped of its barrier layer.
Type of vehicle Used
Skin penetration of drug substance can be enhanced by the use of a
suitable semisolid bases

Example ethyl alcohol generates faster in olive oil than in normal saline as a vehicle
The vehicle generally does not increase the rate of penetration of a drug
substance into the skin, but serves as a carrier for the drug substances that have a
lower solubility in the vehicle are released more readily.
Raw Materials in the Formulation of Medicated Applications
More raw materials are available for use on the skin than for oral use and in
turn more are available for oarl use than parenteral use. There are substance that
can be used topically bu not orally.
The BFAD approves chemical substance and states the maximum
concentration considered safe for food and cosmetics. The supplier of the drug

substances supplies brochures which indicates that BFAD approval safety tests are
made.
Perfumes are not generally included in the formulation of medicated semisolids because many dermatologists objects to its use due to the danger of
sensitization.
The frequent raw materials for medicated semisolids are
1. Hydrocarbons petrolatum and mineral oil are perhaps the most widely used
substance n semisolids next to water
a. Petrolatum is a complex mixture of semisolids containing
hydrocarbon alipathic, cyclic, saturated, unsaturated, branched and
unbranched substance in varying proportions.
b. Mineral Oil is also obtained from petroleum acid, its lower viscosity is
more prederred since it is less tacky.
2. Hydrocarbon Waxes are frequently employed to increase the viscosity of
mineral oil to prevent its separation from an ointment.
Examples: paraffin, ceresin wax (mixture of paraffin and ozokerite)
3. Oieaginous substances vegetable oils such as peanut oil, olive oil, almond
oil, sesame oil are glycerides of mixtures of saturated and unsaturated fatty
acids.
4. Fatty Acids and Alcohols
The commercially available fatty acids are stearic acid and palmitic acids.
a. Stearic acid is used in water removable creams as an emulsifier to
develop a certain consistency in creams.
b. Stearyl alcohol and cetyl alcohol (palmityl alcohol) are used in creams
an auxiliary emulsifier and emollient. In sufficient quantities, stearyl
alcohol produces a firm cream which may be softened by cetyl alcohol.
5. Emulsifiers
The water soluble soaps ( tricthanoiamine striate soap) were among the first
emulsifiers used for semi solids emulsions, of oil in water type. The viscosity
of the cream or oitnmetn prevents coalescence of the emulsified phases and
helps to stabilize the emulsified semisolid.
The interfacial film around the dispersed phase globules is @@@@ solid,
making the emulsified preparation more rigid.
6. Polyols

Glycerins, propyiene glycol, sorbitol 70% and other lower molecular weight PEG
are used as humectants (prevents dehydration and prevents the crusting on top
of ointments and creams)
7. Insoluble Powders
Insoluble powders must be uniformly dispersed throughout the semisolid vehicle
to assure homogeneity of the product. The solids must be impalpable to the
touch otherwise grittiness might result.
Particles less than 74 microns in size equivalent to the number 200 mesh sleeve
are considered impalpable to most people.
Types of Semi-Solid Vehicles
The vehicle used for a semisolid pharmaceutical preparation differs from that
used for a cosmetic, because with cosmetics, skin penetration is not necessary.
A well formulated pharmaceutical semisolid should be both effective
threpaeutically and cosmetically appealing but the major effort mst be in
medical aspect.
Factors which Influence the Choice of Semisolid Vehicles
1. Nature of the Skin lotion
2. Solubility and stability of the drug in the vehicle
Classes of Semisolid Vehicles/Bases Recognized in the USP
1. Hydrocarbon Bases
Petrolatum, white ointment, USP and yellow ointment, USP are typical
lipophilic vehicles.
Petroleum is the most commonly used because of the ff.

Desirable consistency
Ability to spread easily on the skin
Difficult to remove or wash off
Act as occlusive dressings which produces a warm sensation since the
normal evaporation of insensible perspiration is inhibited.

2. Absorption Bases
Absorption bases are hydrophilic mixtures formed by the addition of
substance miscible with hydrocarbons not possessing polar grouping such as
sulfates, sulfonates, carboxyl, hydroxyl or other linkages.
Examples are lanolin, cholesterol, sterols, sorbitan, monostearate, or
monoolcate maybe added to make hydrocarbon bases hydrophilic.

Mineral oil is added to these bases to reduce the tackiness of the

hydrocarbon base.
Cold cream type of water in oil emulsion belongs to this type of ointment
base. The borax-beeswax combination with mineral oil or vegetable oil as
continuous phase. A protective oil film remains on the skin and slow
evaporation of water gives the skin a cooling effect.
3. Water-removable bases
These are oil in water emulsions and are referred to as creams. Vanishing
cream, hand cream, foundation cream and shaving cream belong to this
category, because upon application and rubbing in to the skin, there is little
or no visible evidence of its presence.
Creams may be applied to the moist skin lesions since oil in water vehicle
tends to absorb serious discharges. The vanishing cream type vehicle are
representative of oil in water emulsions whereas the absorption bases are
generally water in oil emulsions.
4. Water soluble bases
These are prepared from mixtures of high and low molecular weight PEG.
Characteristics of water-soluble bases
a. Low molecular weight PEG are liquids moderately high molecular weight
PEG are unctuous semisolids high molecular weight PEG are solids.
b. No water is required for their preparations.
c. Suitable combinations of high and low molecular weight PEG yield
products having an ointment like consistency which softens or melts when
applied onto the skin.
d. These bases are soluble in water due to many polar groups and other
linkages
e. Also known as greaseless ointment bases.
Ophthalmic Ointments
Semisoild ophthalmic vehicles frequently contain soft petroleum jelly, a brand
of absorption base or water soluble base.
All materials added in ophthalmic ointments should be impalpable to avoid
aye discomfort and irritation during application.
Ophthalmic ointments are also rendered sterile and isotonic.
Preservation from Microbial Spoilage
The chemical preservative for semisolids should be evaluated as to:
1. Stability with regard to other components of the formulation
2. Container to be used

Preservatives are added to prevent contamination, deterioration and spoilage by

bacteria and molds. Parahydroxy benozoate esters (Parabens) are used in
combination due to their synergistic action.
General Considerations of Preservatives
Containers may be a contributing source of contamination by harboring
bacterial spores or by sorption or chemical interaction with the preservative like
plastic rubber seals and closures
Characteristics of Preservatives
1. Some preservatives become inactive in the presence of other ingredients
Example: 5% TWEEN 8C inactiveness 80% of the total methyl paraben
present such that the higher concentration of the preservative is required.
2. Each acid may be used in ophthalmic preparations against bacterial or fungal
contaminations
3. Bacterial counts should be made on the water supply raw materials, pipeline,
filling equipment and containers.
Use of Antioxidants
Antioxidants are added to semisolids whenever oxidative deterioration is
anticipated
The choice of antioxidant is made depending on several factors such as:
a.
b.
c.
d.
e.
f.
g.

Toxicity
Irritating potency
Compatibility
Odor
Discoloration
Solubility
Stability

Examples of antioxidants are BHA, BHT and propyl gallate.

Industrial Processing
In pilot plant or small scale production equipment is essential in developing a
manufacturing procedure for a production size batch.
Mixing and stirring operations are critical in the preparation of semisolids.
Aeration should be prevented for stability and consistency in density. This can
be done by introducing one phase below the surface of the other liquid or phase
then mixing carefully.
In filling the lubes, the hopper should be filled with the product an auger-type
of filling machine is used to prevent incorporation of air into container.

Manufacture of Semisolids
Fusion Method anhydrous ointments are manufactured by this process, which is
made by dissolving the active ingredient in the previously melted fats and waxes.
The melted mass must be mixed while cooling to ensure homogenous distribution
on the ingredients.
Factors to be Controlled during Manufacture of Semisolids
1. Time of mixing
2. Temperature of mixing
3. Mechanical works including rate of agitation
Steps in the Manufacture of Semisolid
1. Preparation of the oil and aqueous phases
The components of the oil lipid mixture are laced into the stainless steelsteam jacketed tank melted at a temperature range of 70 to 75 Celsius and
mixed.
The oil phase is transferred to the emulsion mixing tank, those walls have
been heated to the required temperature by gravity or pump.
The components of the aqueous phase are dissolved in the purified water and
filtered.
2. Mixing of the oil and the aqueous phases
The phases are usually mixed at a temperature range of 70 and 72 Celsius
because at this temperature intimate mixing liquid phases occur.
The oil and aqueous phases can be mixed in three (3) ways
a. Simultaneous blending of the phases using a proportioning pump and
continuous mixer, this is good for continuous large batch productions.
b. Addition of the discontinuous phase to the continuous phase useful for
emulsion systems with a low internal or dispersed phase.
c. Addition of the continuous phase to the discontinuous phase useful for
many emulsion systems with a low external or dispersion phase, which
results in a finer disperse volume phase.
3. Cooling of the semisolid emulsion
The rate of cooling is generally slow to allow for adequate mixing while the
emulsion is still liquid.

The temperature of the cooling medium in the jacketed tank should be

decreased gradually at a consistent rat to prevent formation of congealed
masses of the ointment or cream
If perfume or any volatile ingredient is to be added, it is best done at a
temperature of 43 to 45 Celsius to facilitate dissolution of the perfumed oil
4. Homogenization
Two purposes of homogenization
a. For uniform dispersion of an insoluble drug in a semisolid vehicle
b. For reduction of the size of fatty aggregates by passage of the warm
ointment or cream through a homogenizer until 30 to 40 Celsius
5. Storage of semisolids while awaiting completion of QC tests
It is usual practice to store semisolids until the specified Quality Control tests
have been completed and approved, before filling into jars and tubes.
6. Transfer of the Product for Filling and Packaging
The semisolid product may be gravity fed, if it is a two level operation or
pumped to a filling equipment. The semisolid is converted into a liquid by
warming again.

CHAPTER VII
STERILE PRODUCTS
Considered in this chapter is an important pharmaceutical dosage form that
has a common characteristic of being prepared as sterile that is free from
contaminating organisms
Among these sterile dosage forms are:
1.
2.
3.
4.
5.
6.

Various small and large volume parenteral or injectable

Irrigation fluids intended to bathe body wounds or surgical openings
Ophthalmic preparations placed in the sensitive tissues of the eyes
Dialysis solutions
Biological preparations such as vaccines, toxoids, anti-toxins, serums etc.
Other injectable such as pellets or implants

Sterility in these preparations is of utmost importance, since they are directly

placed in direct contact with the internal body fluids or tissues where infections
can easily arise.
Further discussions
Injections/Injectable

They are broadly defined sterile, pyrogens preparations intended to be

administered parentally.
The term pyrogens are fever producing organic substances arising from
microbial contamination and are responsible of the febrile reactions which occur
in patients following intravenous injections.
Conditions/Situations when Parenteral Routes are Undertaken
1. When rapid drug action is desired as in emergency cases
2. When the patient is uncooperative, unconscious or unable to accept or
tolerate medication by oral route
3. When the drug itself in ineffective by other routes
Characteristics of Injectibles
1. They are most frequently in a form of solutions or suspensions or maybe
pellets for tissue implantation
2. Because they are introduced into one or more layers of the skin or mucous
membrane or into internal body compartments they must be:
a. Free from microbial contaminants
b. Free from toxic components
c. Of exceptional high level of purity
Therefore all components and processes involved in the preparation of these
products must be selected and designed to eliminate contamination of all
types whether physical, chemical or microbiological origin.
A. Small Volume Parenteral
These injectable is packaged in small impules or vials with Fill volumes of as
little as 0.5 ml to a maximum of 50 ml.
Examples are
1. Caffeine and Sodium Benzoate Injection cardiac and respiratory
stimulant
2. Procaine hydrochloride Injection local anesthetic
3. Insulin Injection for diabetes
B. Large Volume Parenteral
These injectable is packaged in collapsible bags or 1 liter size vials. They are
administered in volumes of 100 ml to 1000 ml amounts and more per day by
small IV drip sets with or without controlled rate infusion systems.
Characteristic of Large Volume Parenteral
1. They should not contain bacteriostatic agents or other pharmaceutical
additives
2. They are packaged in large single dose containers