dispersed system (ointment and bases).ppt

DISPERSED SYSTEMS 15/03/2013
Transdermal Drug Delivery Systems:
Ointments, Creams, and other
preparations.
Reference: Pharmaceutics: the science
of dosage form design by Aulton M.E.

DISPERSED SYSTEMS
Objectives:
 To define all types of semi-solid
dispersed systems
 To apply the various methods of
formulation,
 To identify properties and uses of
the systems

Dispersed systems cont.
Generally,, transdermal drug delivery
systems, ointments, creams, Lotions
and topical solutions represent the
major frequently used dermatological
dosage forms. Other include pastes,
liniments, powders, gels, tinctures and
aerosols are also commonly used

 Preparations are applied to the skin either for
their physical effect like acting as skin
protectants, lubricants, and emollients, drying
effect or for the specific effect of the medicinal
agent(s) present.
 Preparations are sold over the counter, contain
mixtures of medicinal substances used in the
treatment of such conditions as minor skin
infections, itching, burns, diaper rash, insect
stings and bites, athletes foot corns, calluses,
warts, dandruff, acne, psoriasis and eczema.

 Skin preparations that require prescription
generally contain a single medicinal agent
intended to counter a specific diagnosis
condition.
 Generally drugs used in the treatment of skin do
not penetrate the skin into blood circulation.
This only happed when the drug penetrate the
epidermis. This can be evidenced by detection
in blood and in urinary excretion or metabolites

PERCUTANOUS ABSORPTION
 Absorption of substance from outside
the skin to positions beneath the skin,
including entrance into the blood stream
is referred to as percutaneous
absorption.

 The percutaneous absorption of a
medicinal substance present in a
transdermal therapeutic system or in a
dermatological preparations depends
not only upon the physical and chemical
properties of the medicinal substance,
but also upon its behavior when placed
in the pharmaceutical vehicle and the
condition of the skin.

 It is known that although a
pharmaceutical vehicle may not penetrate
the skin to any great extent nor actually
carry the medicine through the skin, the
vehicle does influence the rate and degree
of penetration of the drug and the degree
and rate vary with different drugs and with
different vehicles

 Therefore each drug – vehicle
combination must be
examined/studied/researched
individually for percutaneous
absorption and therapeutic efficacy.

THE SKIN
The structure of the skin is made of:
 1. Horny layer – dead epidermal cells or
stratum corneum, covered by an emulsion
firm.
 2. Beneath – this layer is living epidermis
or the stratum germinativum
 3. Dermis or true skin.
4. Subcutaneous fat tissue

5.Sweat glands are in the subcutaneous
tissue. The glands yield their products
through the sweat duct which finds their
way to the surface of the skin.
6. Sebaceous gland and hair follicles
originating in the dermis and
subcutaneous layers and also find their
way to the surface.

PENETRATION OF THE SKIN BY DRUGS
After topical application, drugs may penetrate
intact skin through the walls of the hair
follicles, and sweat glands, or sebaceous
glands or between the cells of the horny
layer. Broken or abraded skin, allow drug
penetration easily but such penetration does
not really show true percutaneous
absorption.

The film on top of this layer does not
affect penetration of drug through
the epidermal layer because the film
is not a true barrier as it has no
definite composition, thickness, or
continuity.

Stratum corneum – 1.0 – 1.5 mm, composed of
40% protein,(keratin) and 40% water with the
balance being lipids. The lipids content is
concentrated in the extra cellular phase of
subcutaneous and the lipids play a role in the
first step of the absorption process.
Drugs pass through deeper epidermal layer
tissues and into the dermis. Then it reaches
the vascularized dermal layer and become
available for absorption into general
circulation.

Sc behaves as a semi permeable artificial
membrane and drug molecules penetrate by
passive diffusion.
The rate of drug movement across this skin
layer is dependent on:
 The drug concentration in the vehicle
 Drug aqueous solubility
 Its oil/water partition coefficient between the
sc and the vehicle

Substances that possess both aqueous and lipid
solubility characteristics are good candidates for
diffusion through the stratum corneum as well as
through the epidermal and dermal layers.
Permeation of the skin or laminate barriers
occurs by diffusion via:
 Transcellular penetration (across the cells)
 Intercellular penetration (between cells)
 Trans-appendage penetration (via hair follicles
sweat and sebum glands and pilosebaceous
apparatus).

FACTORS AFFECTING PERCUTANEOUS
ABSORPTION
The factors include:
 Nature of the drug itself
 Nature of the vehicle
 Condition of the skin
 Presence of moisture (hydration)

Through research a consensus on the
combination of drug, vehicle and skin
condition are summarized as follow:
1. Drug concentration in the vehicle.
Percutanous absorption increase with increase
concentration of drug in the vehicle.
2. Large surface area of application and Drug
affinity.
Drug should have more affinity to the skin than
to the vehicle for the drug to leave the vehicle
for absorption in favor of the skin.

3. Degree of solubility of the drug. Solubility of
the drug in both lipid and water is essential
for effective percutaneous absorption.
Agueous solubility determine the
concentration presented to the absorption
site and partition coefficient strongly
influences the rate of transport across the
absorption site. Solute with mw below 800 to
100 with adequate solubility in mineral oil and
water (>1mg/ml) can permeate skin.

4. Drug absorption appears to be enhanced from
vehicles that easily cover the skin surface, mix
readily with the sebum, and bring the drug into
contact with the tissue cells for absorption.
5. Vehicles that increase hydration of the skin
generally increase percutanous absorption of
drugs. Oleaginous vehicles and/or occlusive
bandages act as moisture barriers therefore
hydrate the skin.

6. Generally, the amount of rubbing in or
inunctions of the topical application will
have a bearing on amount of drug
absorbed and this is increase with
prolonged time of inunctions.
7. The percutaneous absorption increase
with thin horny layer, thus the site of
application play a role in drug
absorption.

Beside the thickness of horny layer in
different site of the body, the properties
of the sc vary from different sites of
body including:
 Differences in number of cell layers
 Stacking of cells
 Size of cells
 Amount of surface lipids

8. Time of contact of the application and
the skin absorption is increased. The
longer the time the more the absorption.
9. Multiple-application dosing rather than
single bolus application can increase
drug absorption and bioavailability.

 Age: A newborn skin and very old
skin has very little difference. An
infant and adult skins are
indistinguishable. The blood levels
of drugs following topical application
may be higher in infants than in
adults due to a greater body surface
to volume ratio.

OINTMENT
Ointments are semisolid preparations intended
for external application. Those intended for
application to the eye are specifically prepared
and are termed ophthalmic ointments.
Ointments can be medicated or non-medicated,
the later being referred to as ointment bases
and used as such as:
 For their emollient or lubricating effect
 Used as vehicle in the preparation of medicated
ointment

OINTMENT BASES
They are classified into four general groups:
1. Hydrocarbon bases
2. Absorption bases
3. Water-removable bases
4. Water soluble bases

HYDROCARBON BASES (Oleaginous
bases)
These are water-free and aqueous
preparations may be incorporated
into them only in small amounts and
then with difficulty. Are used for
their emollient effect.

Dispersed systems cont
Properties:
Are retained on the skin for long period
Do not permit escape of moisture from
skin to the atmosphere occlusive
dressings
Are difficult to wash off
Do not dry out or change noticeably
upon aging

1. Petrolatum USP
A mixture of semisolid hc obtained from
petrolatum. It is unctuous mass, varying in
color from yellowish to light amber. Melting
temperature between 380 and 600C. Can be
used at lone or in combination with other agents
as an ointment base.
Synonyms: Yellow petrolatum: Petrollatum jelly
commercial product. Vaseline (Chesebrorough-
Pond’s)

1. White Petrolatum USP:
Is a petrolatum that has been decolorized, it
differs only in this respect to petrolatum and is
used for the same purpose. It is more
esthetically acceptable to patients. Because of
its occlusive, no water-washable
characteristics, it is particularly useful to treat
diaper rash (impervious to mine and protect the
baby’s skin) and dry skin (helps the skin retain
moisture).
Synonyms: White Petrolatum jelly
Commercial product: White Vaseline

2. Yellow Ointment: USP:
Content: Yellow wax: 5%
Petrolatum 95%
Yellow wax is the purified wax obtained from
the honey comb of the bee (Apis mellifera)
Synonyms: Simple ointment.

3. Mineral Oil:
Is a mixture of liquid hydrocarbons
obtained from petrolatum. It is useful as
a levigating substance to wet and to
incorporate solid substance e.g. Salicylic
acid, zinc oxide, into the preparation of
ointments that consists of oleaginous
bases as their vehicle. Synonym liquid
Petrolatum.

ABSORPTION BASES
They are of two types:
Those that permit the incorporation of aqueous
solutions, resulting in the formation of water in
oil emulsions (e.g. Hydrophilic Petrolatum and
Anhydrous Lanolin).
Those that are already water-in-oil emulsion
(emulsion bases) that permit the incorporation
of small additional quantities of aqueous
solutions (e.g. Lanolin and Cold Cream)

ABSORPTION BASES cont.
These bases are useful as emollients but as
occlusive as the oleaginous base. They are not
easily removed from the skin with water
washing.
 It is pharmaceutically useful in incorporating
aqueous solutions of drugs into oleaginous
bases. Incorporate the aqueous 50% in the
absorption base, and then this mixture is added
into the oleaginous base. Example is
gentamycin sulfate for ophthalmic therapy.

1. Anhydrous Lanoline
Contain 0.25% water. Anhydrous lanolin is
insoluble in water but mixes without
separation with about twice its weight of water.
The resultant mixture with water is water-in-oil
emulsion. It is useful as vehicle for application
of comp. Tincture of benzoic and sucrose is
used to treat decubitus ulcers, i.e. bedsores. It
is rolled onto the skin lesion with a colon
swab.
Synonym: Hydrous wool fat.

2. Hydrophilic Petrolatum:
It is composed of cholesterol, stearyl alcohol,
white wax and white petrolatum. It has the
ability to absorb water with the formation of a
water-in-oil emulsion. Aquaphor is a highly
refined variation of hydrophilic petrolatum and
because it can absorb up to 3 times its weight
in water. It is useful to pharmacists who have
to incorporate extemporaneously a water-
soluble drug into an oleaginous base.

3. Lanolin
A semisolid fat like substance obtained
from the wool of sheep (Ovis Aries). It is a
water-in-oil-emulsion containing between 25
and 30% water. Additional water can be
incorporated into lanolin by mixing.
Synonym: Hydrous wool fat.

Cold Cream:
Is a semisolid, white water-in-oil emulsion
prepared with cetyl esters wax, white wax,
mineral oil, and sodium borate and purified
water. The sodium borate combine freely with
the free fatty acids present in the waxes to
form sodium soap that acts as the emulsifiers.
Cold cream is used as an emollient and
ointment base. The presence of water in the
base is useful onto the skin and enhances
moisturization of the skin.

WATER REMOVABLE BASES
These are oil-in-water emulsions that are capable
of being washed from skin or clothing with
water. Thus referred to as “water-washable”
ointment bases. These bases can be diluted
with water or aqueous solutions.
Therapeutically they have the ability to absorb
serous discharges in dermatological conditions.
The skin better absorbs drugs incorporated in
these bases than the other types.

1. Hydrophilic ointment
It is water-loving base. It contains sodium
lauryl sulphate as an emulsifying agent, with
stearyl alcohol and white petrolatum
representing the oleaginous phase of the
emulsion and propylene glycol and water
representing the aqueous phase. Methyl
paraffin and propylparaffin are used to
preserve the ointment microbial growth. The
ointment is used a water removable vehicle for
drugs

WATER SOLUBLE BASES
It contains only water-soluble components. They
are water washable, referred as “greaseless”.
They good for incorporation of non aqueous or
solid substances.
1. Polyethylene Glycol ointment
It is formulated by combining:
Polyethylene glycol 3350 – 400g
Polyethylene (liquid) 400 – 600g
Total 1000g

If a firmer ointment is required, equal amounts
of the 2 ingredients are used. If 6 – 25% e.g.
solution is to be incorporated into the base, 50g
of polyethylene glycol 3350 is substituted with
stearyl alcohol to render the final product
firmer.
Polyethylene glycols are polymers of ethylene
oxide and water represented by the formula
HOCH2(CH2OCH2)n CH2OCH. The chain length
may be varied to achieve polymers having
desired viscosity and physical (liquid semisolid
or solid) form.

SELECTION OF THE APPROPRIATE BASE
The selection of the base for use in a formulation
depends on careful assessment of a number of
factors, which include:
The advisability of occlusion of moisture from
the skin by the base.
The desirability for enhancement by the base of
the percutaneous absorption of the drug.

 The influence if any of the drug on the consistency or
other features of the ointment base.
 Natures of the patients skin – dry or wet.
 The long term and short-term stability of the drug in the
ointment base.
PREPARATION OF OINTMENTS
Both on a large or small scale, ointments are prepared
by two general methods.
1. Incorporation or mechanical
2. Fusion

 Incorporation:
In this method, the components are
mixed together by various means until a
uniform mixture has been attained. In a
small scale, as in extemporaneous
compounding of prescriptions, the
components are mixed in a mortar using
a pestle or on a slab-using spatula

(a) Incorporation of solids:
When preparing ointment by spatulation a
pharmacist use large long broad spatula stainless
steel and a small spatula use to remove the
accumulation of ointment on the large spatula
periodically.
If the components of the ointment are reactive with
the metal spatula then a plastic one is used. The
solids are first reduced to fine particles in a motor.
Then the base is put on one side of the slab and
the powders on the other side.

Then mixing is done geometrically until you
obtain a uniform mixture of ointment.
Sometimes the powder particles are reduced
then navigated using vehicle which will be
compatible with both the drug and the base
like mineral oil, glycerin, then is mixed with a
portion of the base on equal bases. After
lavigation the dispersion is incorporated with
the remaining base by spatulation or mortar
and pestel.

Solid materials soluble in a common
solvent that will affect neither the
stability of the drug nor the efficacy of
the product may first be dissolved in that
solvent, then the solution added to the
ointment base by spatulation or by
mortar and pestle. Mortar and pestle is
preferred if the liquids are more.

dispersed system (ointment and bases).ppt

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