DEFINITION:
Semi solids are the topical dosage form used for the therapeutic,
protective or cosmetic function. They may be applied to the skin, or used nasally,
vaginally, or rectally.
IDEAL PROPERTIES OF
SEMISOLID DOSAGE FORMS :
PHYSICAL PROPERTIES
- ·
Smooth
texture
- ·
Elegant
in appearance
- ·
Non
dehydrating
- ·
Non
gritty
- ·
Non
greasy and non staining
- ·
Non
hygroscopic
PHYSIOLOGICAL PROPERTIES
- · Non
irritating
- · Do
not alter membrane / skin functioning
- ·
Miscible
with skin secretion
- · Have low sensitization index
APPLICATION PROPERTIES
- · Easily applicable with efficient drug release.
- · High aqueous washability.
ADVANTAGES:
Avoid of first pass metabolism. Site specific action of drug on
affected area. Convenient for unconscious patient or patient having difficulty
on oral administration. Suitable dosage form for bitter drugs. More stable than
liquid dosage form.
DISADVANTAGES:
May cause staining. They are bulky to handle. Application with
finger may cause contamination. Physico-chemically less stable than solid
dosage form. May cause irritation. Allergic to some patients.
CLASSIFICATION:
- ·
creams
- ·
poultice
- ·
gels
- ·
pastes
- ·
ointments
- ·
suppositories
- ·
plasters
non-sterile sterile
OINTMENTS
Homogeneous, translucent, viscous, semi-solid preparation, most
commonly a greasy, thick oil (oil 80% - water 20%) with a high viscosity,
Applied to the skin or mucous membranes.
Uses Emollients application of active ingredients to the skin Occlusive
CREAMS
Viscous semisolid emulsion system with opaque appearance as
contrasted with translucent ointments.
Consistency depends on weather the cream is w/o or o/w. W/O creams
O\W creams Contains lipophilic emulsifying agent.
Used as emollient and as cleansing agent.
Contains O\ W emulsifying agent.
O/W creams are elegant drug
delivery system.
PASTES
Contains high percentage of insoluble solid (usually 50 % or more)
Pastes are usually prepared by incorporating solids directly into
a congealed system by levigation with a portion of the base to form a paste
like mass.
They have good adhesion on skin and less greasy.
GELS AND JELLIES
Gels and jellies are semisolid system in which a liquid phase is
constrained within a 3-D polymeric matrix having a high degree of physical or
chemical cross-linking. Gels are aqueous colloidal suspensions of the hydrated
forms of insoluble medicament. Jellies are transparent or translucent
non-greasy semisolid and contains more water than gels. Used for medication,
lubrication and carrier for spermicidal agents to be used intra vaginally with
diaphragms.
POULTICES (CATAPLASMS)
They are wet masses of solid matter applied to the skin in order
to reduce inflammation and in some cases to act as a counter-irritant. Poultice
must retain heat for a considerable time. After heating the preparation is
spread on dressing and applied to the affected area. E.g. Kaolin poultice
(B.P.C.)
PLASTERS
Plasters are solid or semisolid masses made by incorporating
medicaments in resinous or waxy bases which are melted and spread on suitable
backing material they are mainly used to, Afford protection and mechanical
support. Furnish an occlusive and macerating action. Bring medication into
close contact with the surface of the skin.
SUPPOSITORIES
It is solid or stiffened semisolid dosage form intended for
insertion into body orifices where they melt, soften, or dissolve and exert
local or systemic effects.
TYPES
(1) Rectal suppositories
(2) Pessaries
(3) Urethral bougies
(4) Nasal bougies
(5) Ear cones
FORMULATION OF SEMISOLID
DOSAGE FORMS :
INGREDIENTS USED IN
PREPARATION OF SEMISOLIDS
(1) Active pharmaceutical
ingredient (API)
(2) Bases
(3) Preservative
(4) Humectants
(5) Antioxidants
(6) Emulsifier
(7) Gelling agent
(8) Permeation enhancer
(9) Buffers
1. BASES:
It is one of the most important ingredient used in formulation of
semisolid dosage form. Ointment and suppository bases do not merely act as the
carriers of the medicaments, but they also control the extent of absorption of
medicaments incorporated in them. 16
IDEAL PROPERTIES OF A BASE:
They should be, Inert, non-irritating and non-sensitizing.
Compatible with skin pH and the drug. Good solvent and/or emulsifying agent.
Emollient, protective, non-greasy and easily removable. Release medicament
readily at the site of application. Pharmaceutically elegant and possess good
stability.
TYPES OF BASES:
A. Oleaginous bases.
B. Absorption bases.
C. Emulsion bases.
D. Water soluble bases.
A) Oleaginous (hydrocarbon)
bases. :
They consist of a combination of more than one oleaginous material
such as water-insoluble hydrophobic oils and fats. They are highly compatible;
occlusive; good emollients. They are anhydrous, do not absorb water, readily
(hydrophobic) insoluble in water, not washable. Examples: Vaseline, hard
paraffin, liquid paraffin, white ointment.
Uses: protectants, emollient, and vehicle for solid drugs.
B) Absorption
(Emulsifiable) Bases :
Have capacity to absorb considerable quantities of water or
aqueous solution and turn to w/o without marked changes in consistency. They
are anhydrous, water insoluble and water unwashable. They have good emollient
but poor occlusive property.
Uses: protectants, emollient, and vehicle for aqueous solutions and
solid drug.
C) Emulsion Bases :
According to the type of emulsion, these bases are classified as
either W/O or O/W.
Uses: Cleansing creams, emollients and vehicle for solid and liquid
drugs.
Emulsion Ointment Base (W/O):
·
Hydrous
·
Will
absorb water
·
Insoluble
in water
·
Not
washable
·
Water-Oil-Emulsion
Emulsion Ointment Base (O/W):
·
Hydrous
·
Will
absorb water
·
Insoluble
in water
·
Washable
·
Oil-in-Water
Emulsion
·
Hydrophilic
Ointment
D) Water Soluble Bases :
These include both anhydrous and hydrous dermatological
non-emulsion bases which are water soluble and contain no oil phase. Water
soluble, water washable, greaseless. Because they soften with the addition of
water, large amounts of aqueous solutions are not effectively incorporated into
these bases. Examples . Carbowax compounds such as the polyethylene glycol
bases containing pectin, cellulose, Bentonite, and gelatin.
2. PRESERVATIVE:
Some base, although, resist microbial attack but because of their
high water content, it require an antimicrobial preservative. Commonly used
preservatives include Methyl hydroxybenzoate Propyl hydroxybenzoate
Chlorocresol Benzoic acid Phenyl mercuric nitrate
3. ANTIOXIDANTS :
Oxygen is a highly reactive atom that is capable of becoming part
of potentially damaging molecules commonly called “free radicals.” Free
radicals are capable of attacking the healthy cells of the body, causing them
to lose their structure and function. To prevent this an antioxidants are
added. E.g. Butylated hydroxy anisole, Butylated hydroxy toluene.
4. GELLING AGENTS :
Gelling agents, forms a gel, dissolving in the liquid phase as a
colloid mixture that forms a weakly cohesive internal structure. These are
organic hydrocolloids or hydrophilic inorganic substances.
E.g. Tragacanth, Sodium
Alginate, Pectin, Starch, Gelatin, Cellulose Derivatives, Carbomer, and Poly
Vinyl Alcohol Clays.
Material % Brookfield
viscosity ‘CP 0’ Carbomer 941resin NF Carbomer 941resin NF Guar gum Methyl
cellulose Sodium alginate 0.15 0.25 1.50 2.00 2.50 2900 6300 8040 5200 10400
5. PERMEATION ENHANCERS :
Skin can act as a barrier. With the introduction of various
penetration enhancers, penetration of the drug through the skin can be
improved. Sr. no Permeation enhancer Drugs used
1. Menthol, carvacrol, linalool Propranolol hydrochloride
2. Limonene Indomethacin, ketoprofen
3. Geraniol, nerolidol Diclofenac sodium
4. Oleic acid Piroxicam
6. EMULSIFIER :
An emulsifier (emulgent) is a substance that stabilizes an
emulsion by increasing its kinetic stability. One class of emulsifiers is known
as surface active substances, or surfactants. Ideal properties of emulsifier
includes,
a) Must reduce surface tension for proper emulsification.
b) Prevents coalescence and should quickly absorb around the
dispersed phase.
c) Ability to increase the viscosity at low concentration.
d) Effective at low concentration
7. HUMECTANT:
A humectant is a hygroscopic substance. It is often a molecule
with several hydrophilic groups, most often hydroxyl groups. Since hygroscopic
substances absorb water from the air, they are frequently used in desiccation
or for humidity buffering.
Humectants are used to :
·
increase
the solubility of the active ingredient.
·
to
elevate its skin penetration.
·
the
hydration of the skin.
8. BUFFERS:
Buffers are added for various purpose such as : Compatibility with
skin. Drug solubility. Drug stability. Influence ionization of drug. Skin, due
to its weak acidic nature, tolerates weak acidic preparations. E.g. sodium
acetate, sodium citrate, potassium metaphosphate.
9. VEHICLE:
Purified water, water for injection, Water for injection may be
used in ophthalmic semi solid preparations like eye ointment, gels etc.
METHODS OF PREPARATION:
A. TRITURATION
This method is also known as levigation, incorporation or
mechanical mixing. When base contain soft fats and oils or medicament is solid
and insoluble or liquid, then this method is use.
B. FUSION
This method is used :-
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.
Solid drugs that are readily soluble in melted base.
C. CHEMICAL REACTIONS
In chemical method a new product is formed by chemical reaction,
which involves both fusion and mechanical mixing. Best example of such method
is Iodine ointment. E.g. Ointment containing free iodine Iodine is only
slightly soluble in most fats and oils. Iodine is readily soluble in
concentrated solution of potassium iodide due to the formation of molecular
complexes KI.I 2 , KI.2I 2 , KI.3I 2 etc. These solutions may be incorporated
in absorption-type ointment bases. 38
EVALUATION OF SEMI SOLID
DOSAGE FORM:
(1) Physical methods
Test
of rate of absorption
Test
of non-irritancy
Test
of rate of penetration
Test
of rate of drug release
Test
of rheological properties
Test
of content uniformity
(2) Microbiological methods
Test
of microbial content
Test of preservative
efficacy
PHYSICAL METHODS:
1.TEST OF RATE OF ABSORPTION
The ointment should be applied over a definite area of the skin by
rubbing. At regular intervals of time, serum and urine samples should be
analyzed for the quantity of drug absorbed.
2. TEST OF NON-IRRITANCY
Non-irritancy of the preparation is evaluated by patch test. In
this test 24 human volunteers are selected. Definite quantity of ointment is
applied under occlusion daily on the back or volar forearm for 21 days. Daily
the type of pharmacological action observed is noted. No visible reaction or
erythema or intense erythema with edema and vesicular erosion should occur. A
good ointment base shows no visible reaction.
3. TEST OF RATE OF PENETRATION
Flow-through diffusion cell or microdialysis method is used.
Animal or human skin of definite area should be collected and tied to the
holder present in a diffusion cell. The diffusion cell is placed in a fluid
bath. Measured quantity of the preparation is applied over the skin and the
amount of drug passed into the fluid is measured at regular intervals by
analyzing the aliquots of fluid using a spectrophotometer.
4. TEST OF RATE OF DRUG RELEASE
A clean test tube is taken and the internal surface is coated with
the preparation as a thin layer. Saline or serum is poured into the test tube.
After a certain period of time, the saline is analyzed for the quantity of the
drug. The amount of drug when divided by the time period gives the rate of drug
release.
5. TEST OF RHEOLOGICAL PROPERTIES
The viscosity of the preparation should be such that the product
can be easily removed from the container and easily applied to the skin. Using
cone and plate viscometer the viscosity of the preparation is determined.
MICROBIOLOGICAL METHODS:
1. TEST OF MICROBIAL CONTENT
Solutions of different samples of the preparation are made. Each
sample is inoculated into separate volumes of 0.5 ml of rabbit's plasma under
aseptic conditions and incubated at 37 0 C for 1-4 hours. No formation of the
clot in the incubated mass indicates the absence of the micro-organisms.
2. TEST OF PRESERVATIVE EFFICACY
Using pour plate technique the number of micro-organisms initially
present in the preparation are determined. Solutions of different samples of
the preparation are made and mixed with Tryptone Azolectin (TAT) broth
separately. All cultures of the micro-organisms are added into each mixture,
under aseptic conditions. All mixtures are incubated. The number of
micro-organisms in each sample are counted on 7th, 14th, 21st and 28th days of
inoculation.
REFERENCES:
Cooper and Gunn’s ; Dispensing for Pharmaceutical Students; 12 th
edition; CBS publishers and distributors Pvt. Ltd; 192-229. Atamaram Pawar and
R.S. Gaud; Modern Dispensing Pharmacy; 1 st edition; Career Publications;
199-232. Leon Lachman, Herbert A. Lieberman, Joseph H. kanig; The Theory and
Practice of Industrial Pharmacy; 3 rd edition; Varghese publication; 534-563.
Dr. A.K. Seth; Pharmaceutics-II (Dispensing and Formulation); S. Vikas and Co.
Publishing house; 262-319. http://www.pharmainfo.net/free-books/novel-semisolid-dosage-forms
http://www.pharmainfo.net/evaluation-ointments
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