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Semisolid Dosage Forms
312 PHT
Objectives
- To introduce the student to the structure, functions
and topical treatment of human skin
- To deal with the principles of membrane diffusion,
skin transport and properties affecting transdermal
delivery
- To identify dermatological vehicles and methods of
preparation
- To identify new trends in semisolid dosage
form
SEMISOLID PREPRATIONS
DEFINITION:
Semisolid dosage forms are products of semisolid
consistency and applied to skin or mucous
membranes for therapeutic or protective action
or cosmetic function.
IDEAL PROPERTIES OF SEMISOLID
DOSAGE FORMS
1.PHYSICAL PROPERTIES: a) Smooth texture
b) Elegant in appearance
c) Non dehydrating
d) Non gritty
e) Non greasy and non staining
f) Non hygroscopic
IDEAL PROPERTIES OF SEMISOLID
DOSAGE FORMS
2. PHYSIOLOGICAL PROPERTIES: a) Non irritating
b) Do not alter membrane / skin functioning
c) Miscible with skin secretion
d) Have low sensitization effect
3. APPLICATION PROPERTIES: a) Easily applicable with efficient drug release
b) High aqueous washability
TYPES OF CONVENTIONAL SEMISOLID
DOSAGE FORMS
1. OINTMENTS:- They are soft hydrocarbon based semisolid
preparations, e.g. pertrolatum.
- Since they are mostly of greasy nature so they stain
cloths, are generally poor solvent for most drugs, and
usuallydecrease the drug delivery capabilities of
the system.
TYPES OF CONVENTIONAL SEMISOLID
DOSAGE FORMS
2. CREAMS : - They are viscous semisolid emulsion system with
opaque appearance compared with the translucent
ointments. Consistency and rheological characters
depend on weather the cream is w/o or o/w.
- Properly designed O/W creams are elegant drug
delivery system, pleasing in both appearance and feel
aftar pplication.
- O/W creams are non greasy and are rinsable.
They are good for most topical purposes
TYPES OF CONVENTIONAL SEMISOLID
DOSAGE FORMS
3. PASTES:- Pastes are basically ointments into which a high
percentage of insoluble solid has been added.
The extraordinary amount of particulate matter
stiffens the system.
- Pastes make particularly good protective barrier
when placed on the skin chemicals before they
ever reach the skin.
- Like ointments, paste forms an unbroken
relatively water – impermeable film. Unlike
ointments, the film is opaque and therefore, an
effective sun block accordingly.
TYPES OF CONVENTIONAL SEMISOLID
DOSAGE FORMS
4. GELS (JELLIES) :- Gels are semisolid coherent system in which a liquid
phase is constrained within a polymeric matrix
(consisting of natural or synthetic gum) having
high degree of physical or chemical cross-linking.
- Gels are aqueous colloidal suspensions of the
hydrated forms of insoluble medicament.
- Gels are transparent or translucent non-greasy
semisolid gels.
- They are used for medication or
lubrication.
TYPES OF CONVENTIONAL SEMISOLID
DOSAGE FORMS
5. POULTICES:It is soft, viscous, pasty preparation for external use. They
are applied to skin while they are warm, after spreading
on or between layers of cloth . Poultice must retain heat
for a considerable time because they are
intended to supply warmth to inflamed parts
of body.
- Poultices act by increasing blood flow, relaxing tense
muscles, soothing inflamed tissues, or drawing toxins
from an infected area. Thus, they can be used to relieve
the pain and inflammation associated with abscesses; e.g.
Kaolin poultice (B.P.C.)
TYPES OF CONVENTIONAL SEMISOLID
DOSAGE FORMS
7 SEMISOLID FOAMS:- Foams are system in which air or some other gas is
emulsified in liquid phase to the point of stiffening.
- E.g. shaving creams, whipped creams, aerosolized
shaving creams.
- Conventional topical vehicles, such as ointments,
creams or gels, predominantly exert their effect by
releasing the drug onto the skin surface, and the drug
molecules then diffuse through the skin layers.
- The extent and duration of diffusion depends on
the (1) physicochemical properties of the drug,
(2) the type of base and (3) skin condition.
- In general, the modification of drug absorption
kinetics by these vehicles is the result of their
ability to provide increased hydration by
occlusion or some other mechanism.
Topical preparations
- Preparations for dermal use
- Preparations for transdermal use
(percutaneous absorption)
Dermal and transdermal drug delivery
- Semisolid dosage forms for dermatological drug
therapy are intended to produce desired therapeutic
action at specific sites in the epidermal tissue.
- A drug’s ability to penetrate the skin’s epidermis,
dermis, and subcutaneous fat layers will lead to
transdermal (percutaneous) drug delivery giving rise
to systemic action.
- Therefore, the extent the drug can travel through the
different skin layers determine the delivery system.
Why Transdermal drug delivery?
- Avoiding hepatic first pass effect
- Continuous drug delivery
- Fewer side effect
- Therapy can be terminated at any time
- Improved patient compliances
Disadvantages:
- cosmetically non-appealing
- may display erratic (irregular) absorption
The fraction of the drug that penetrate the skin
via any route depends on:
– The physicochemical nature of the drug, specially its
size, solubility and partition coefficient
– The site and condition of the skin
– The formulation
– How vehicle component temporarily change the
properties of the stratum corneum
Skin Permeability
- Basic principle of diffusion through membranes
Fick’s Law of Diffusion
dQ /dt= )DAK/ h) (C 1-C2)
dQ/dt - rate of diffusion
D - diffusion coefficient
A - surface area of membrane
K - partition coefficient
h - membrane thickness
C1 - C2 = concentration difference for solute
Generally, C1>>C2
Skin Permeability
Since D, K, and h are constant for a given
drug/membrane; and given that C1>>C2:
dQ / dt = PC1
Where P - permeability constant
Ideal molecular properties for drug
Penetration
- A low molecular weight (generally less than 500
Daltons)
- An adequate solubility in oil and water
- A balanced partition coefficient
- A low melting point
- Potent drug (maximum 50 mg/day)
Factors Affecting Transdermal
Delivery
- Physiological factors
- Physicochemical factors
PHYSIOLOGICAL FACTORS
1. Skin condition
– Intact skin is a barrier
– Damaged skin more permeable
– Diseased skin usually more permeable
2. Skin age
- babies and children – greater area/weight than
adult- absorb more drug e.g. steroids
- premature infants- no stratum corneum
- e.g. the use of topical caffeine for breathing
difficulties
PHYSIOLOGICAL FACTORS
3. Skin hydration
- important as it usually promotes permeation
principle factor - Rank order (decreasing): - occlusive film
- ointment
- cream
4. Regional skin site
- wide variation, e.g. face to foot
PHYSICOCHEMICAL FACTORS
1. Temperature and pH
- diffusion depends on temperature(direct relationship).
- nonionic molecules is more permeable than ionic
- Stratum corneum, pH = 4.5 – 6
- How pH affect drug penetration??? ?
PHYSICOCHEMICAL FACTORS
2. Drug concentration
obeys Fick’s law
dQ/dt = KDC/h
3. Partition coefficient
- also obeys Fick’s law
- moderate value (Why????)
4. Diffusion coefficient
5. Molecular size
- absorption should be inversely proportion to size
(M.Wt.)
Topical dosage forms
- Ointments
- Creams
- Pastes
- Gels/jellies
- Solution
- Plasters
- Aerosols
- Powders
Ointments
An ointment is a viscous semisolid preparation used
topically on a variety of body surfaces. These include
the skin and the mucus membranes of the eye (an eye
ointment), vagina, anus, and nose.
An ointment may or may not be medicated.
Typically used as:
Emollients to make skin more pliable
Protective barriers
Vehicles in which to incorporate medication
Ointment
1.2. Ointment Bases
- Semisolid bases do not only act as the carriers of the
medicaments, but they also control the extent of absorption of
medicaments incorporated therin.
- An ointment base should be compatible with skin, stable,
smooth, non-irritating, non-sensitizing, inert, capable of
absorbing water or other liquid preparations, and of releasing
the incorporated medicament, readily.
- A base for ophthalmic semisolids must be non-irritating to the
eye, and It should also be sterilizable conveniently.
Appropriate Selection of Ointment Base:
Selection of ointment base depends on the following:
1. Desired release rate of the drug substance from the
ointment base.
2. Rate and extent of topical or percutaneous drug
absorption.
3. Desirability of occlusion of moisture from skin.
4. Stability of the drug in the ointment base.
5. Effect of drug on the consistency of base.
6. Easy removal of base on washing.
7. Characteristic of the surface to which it is applied
Ointment Bases
- Ointment bases may be classified in several
ways but the following classification based on
composition is generally used which are as
follow,
A) Oleaginous (hydrocarbon) base.
B) Absorption base.
C) Emulsion base.
D) Water soluble base.
Ointment bases
A) Oleaginous (hydrocarbon) bases: -This is a purified mix of liquid, semi-solid or
solid hydrocarbons from petroleum
- Most of the early ointment bases used to be exclusively
oleaginous in nature but nowadays
the materials obtained from plant, animal, as
well as synthetic origin are employed as
oleaginous ointment bases.
- Combinations of these materials can produce a
wide range of melting points and viscosities
Ointment bases
A) Oleaginous (hydrocarbon) bases: These bases are:
- Immiscible with water (they are difficult to wash off)
- Not absorbed by the skin, remain on the skin for
prolonged period of time without “drying out”
- Absorb very little water from formulation or from
skin exudates.
- Inhibit water loss from the skin by forming a water
proof film (OCCLUSIVE DRESSING).
- Improving hydration, may encourage penetration of
the medication through skin.
Examples: Vaseline, hard paraffin, liquid paraffin,
white ointment
Uses: protectants, emollient, and vehicle for solid
drugs
Ointment bases
B) Absorption (Emulsifiable) Bases: Absorption bases (also called emulsifiable
bases) are mostly W/O type emulsions and
have capacity to absorb considerable quantities
of water or aqueous solution without marked
changes in consistency.
Ointment bases
Absorption bases are:
- less occlusive than the hydrocarbon bases.
- Incorporation of aqueous solution is possible.
- easier to spread.
- good emollients
- They hydrate the stratum corneum.
- Not easily removed from the skin with water
washing (external phase is oleaginous)
- Uses: protectants, emollient, and vehicle for
aqueous solutions and solid drugs
Ointment bases (cont.)
Absorption base (cont.)
- Lanolin, anhydrous lanolin, wool fat, wool
wax (obtained from wool of sheep)
- This is a type of wax- like that can absorb about 50%
of its weight of water and is used in ointments in
which the proportion of aqueous fluid is too large for
incorporation into a hydrocarbon base.
- Wool fat is a major constituent of Simple Ointment
BP
- Other examples: hydrous lanolin, bees wax and
cholesterol (they are added to some ointment bases to
increase their water-absorbing power)
Ointment bases (cont.)
(C) Emulsion Bases:
- They are either w/o or o/w
- Hydrophilic Ointment USP
- Cold cream: W/O emulsions, emollient, cleansing, not
water washable, non occlusive, shiny appearance, not
need glycerin.
- Vanishing cream: O/W emulsion contains large % of
water and humectant. An excess of stearic acid in the
formula helps to form a thin film when the water
evaporates.
Ointment bases (cont.)
Properties of Emulsion bases:
- Water-washable, easier to remove
- Non/less greasy
- Can be diluted with water
Non/less occlusive
- Better cosmetic appearance
- Better compliance; Patients prefer cream to an
ointment because the cream spreads more readily,
- less greasy, evaporating water soothes the inflamed
tissue.
Uses: Cleansing creams, emollients and vehicle for
solid and liquid drugs.
D) Water Soluble Bases: - Water soluble and water washable
“greaseless”,
- Because they soften with the addition of water,
large amounts of aqueous solutions are not
effectively incorporated into these bases.
Uses: drug vehicle
D) Water Soluble Bases (cont.): The water-soluble bases have the advantages of
being:
- Water soluble and washable
- Non-greasy, non-staining
- Non/less occlusive
- Lipid free
- Relatively inert
- Does not support mold growth
- Little hydrolysis, stable
-Disadvantages: May dehydrate skin and hinder
percutaneous absorption.
- Polyethylene glycol (so called macrogols or
carbowax) are mixtures of poly-condensation
products of ethylene oxide and water and they are
described by their average molecular weights
(viscous liquids to waxy solids).
- Different grades of cabowaxes are available which
are designated by a number roughly representing
their average molecular weights e.g.- PEG 200,
PEG 400, PEG1000, PEG1540, and PEG 6000
A general rule is that:
- For wet lesions the patient should use an
aqueous dressing,
- For dry skin a lipophilic base is best.
Selection of the appropriate base
- Desired release rate of drug substance
- Desirability for topical or percutaneous
absorption
- Desirability of occlusion
- Stability of drug in ointment
- Effect of drug on ointment base
- Desire for easy removable
METHODS OF OINTMENT PREPARATION
1 BY TRITURATION:In this finely subdivided insoluble medicaments are
evenly distributed by grinding with a small amount of
the base followed by dilution with gradually
increasing amounts of the base.
2 BY FUSION:When soft fats or waxes are to be incorporated with
hard fats or waxes then of this to be melted to get
homogenous mixture with stirring.
- ingredients are melted together in descending order
of their melting points.
3 BY OINTMENT MILLS:It is used for large scale production where triple roller mill is utilized
which is faster than others.
Requirement for ointments
- Microbial content: do not need to be
sterile, but must meet the FDA
requirement of the test for absence of
bacteria such as S. areus and P.
aeruginosa for dermatological
products.
- Packaging, storage, labeling: (label
should include the type of base used)
- Additional standards: viscosity, in
vitro release
CREAM
- Semisolid preparations containing one or
more medicinal agents dissolved in either
an o/w or w/o emulsion or in another type
of water-washable base.
- Typically of low viscosity, two phase
system (w/o or o/w), compared to
ointment.
- Appears “creamy white” due to the
scattering of light.
- Traditionally, it is the w/o cold cream
-Currently and most commonly, it is the o/w
emulsion.
Creams as drug delivery systems
- Good patient acceptance
- Water evaporation concentrates drug on skin
surface
Examples;
Vanishing cream: o/w with high % of water and
stearic
acid.
Cold cream: (an emulsion for softening and
cleansing the
skin): w/o, white wax, spermaceti, almond oil, sodium
borate.
CREAM
EMULSIFIER : -
Important in creams
-Ideal properties of emulsifier includes,
a) Must reduce surface tension for proper
emulsification.
b) Prevents coalescence.
c)Effective at low concentration
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