Clasification Cream

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World Journal of Clinical Pharmacology, Microbiology

Microbiolog and Toxicology


World J. Clin. Pharmacol. Microbiol.Toxicol.
Vol. 1 [1] May 2015; 0926
AELS, India
URL: http//wjcpmt.com

REVIEW ARTICLE

Formulation and Evaluation of Ointment and Cream with Their


Mathematical Treattm
ment of Absorption Through Skin: A Review
Sunil Yadav*, Paras Papneja, Sanjay Batra, Mohit Sharma
Seth Gl Bihani Sd College Of Technical Education Sri Ganganagar
Emai address [email protected]
Email

INTRODUCTION

Ointments and creams are the semisolid dosage forms and intended for topical application to the skin,
placed on the surface of eye, or used nasally, vaginally or rectally for therapeutic or protective acti
action or
cosmetic function. These preparations are used for the localized effects produced at the site of their
application by drug penetration in to the underlying layer of skin or mucous membrane. These products
are designed to deliver drug into the skin in treating dermal disorders, with the skin as the target organ
organ.
[Ansel, Howard C.,et al., (2000)]
Ideal Properties of Semisolid Dosage Form
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
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 wash ability
For the delivery of these semisolid preparations transdermal drug delivery system is designed.

OINTMENT
Ointments are soft, semisolid dermatological preparations intended for application to skin and mucous
membrane for therapeutic or protective
protective action. They may be applied to the skin placed on the surface of
the eye, or used nasally, vaginally, or rectally with or without inunction. Ointments are designed to deliver
drug into the skin in treating dermal disorders, with the skin as the target
targe organ.
Ointments serve mainly three functions.
1) Lubricatingemollients
2) Treat skin disorder (Medicinal effect)
3) Protective coverings [Carter, S.J.,(2000)]

CLASSIFICATION OF OINTMENTS:-
OINTMENTS:
i) According to their therapeutic properties based on penetration
penetra
ii) According to their therapeutic uses [Mehta, R.M., (1997)]
i) Ointments classified according to their therapeutic properties based on penetration
Epidermic ointment:- These are act on epidermis and produce local effect. They are not absorbed.
These ointments are used as protective, antiseptics, local antiinfective
anti infective and parasiticides.

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Endodermic ointment:- These are act on deeper layer of cutaneous tissues. They are Partially
absorbed and act as emollients, stimulants and local irritants.
Diadermic ointments: These ointments are used for deeper penetration and release the
medicaments that pass through the skin and produce systemic effects. [Mithal, B.M.,(1980)]
ii) Ointments classified according to their therapeutic uses
Antibiotic ointment: These are used to kill microorganisms. The antibiotics used are bacitracin,
neomycin, etc.
Antifungal ointments: These are kill the fungi. The antifungal used are benzoic acid, salicylic acid,
etc.
Anti- inflammatory ointments: These are used to relieve inflammation, allergy, pruritic condition
of skin. Betamethasone valerate, hydrocortisone and its acetate are some anti inflammatory agents.
Antipruritic ointment:- These are used to relieve itching. The commonly used agents are benzocain,
coal tar, etc.
Astringent ointment:- These causes contraction of the skin and decrease discharges. The commonly
used agent calamine, ZNO,tannic acid, etc
Antieczematous ointments: These are used to prevent oozing and excreation from vesicle on the
skin. The drugs which are commonly used are hydrocortisone, coaltar, salicylic acid, etc.
Keratolytic ointments: These are used to remove or soften the horny layer of the skin. The drugs
which are commonly used are salicylic acid, sulphur, etc.
Counter- irritant ointments:- These are applied to irritate the skin, thus reduing other irritation or
pain. The drugs which are commonly used are capsicum, methyl cellulose, etc.
Ointments used for dandruff treatment:- These are used to relieve from dandruff. The drugs
which are commonly used are cetrimide, etc.
Ointment for psoriasis treatment:- Coal tar, corticosteroids are incorporated with a suitable
ointment base for treatment of psoriasis.
Parasiticide ointment:- These are destroy or inhibit living infestation, such as lice and ticks. The
drugs commonly mixed with ointment bases are benzyl benzoate. Sulphur, etc.
Protectant ointment: These ointments protect the skin from moisture, air, sun rays or other
substances such as soaps or chemicals. The drugs which are commonly used are calamine, silicones, etc.
[Mehta, R.M.,(1997)]

Figure 1: Ointment
[http://www.google.co.in/imgres?imgurl=http://en.heilkraeuter.net/ointment/rescueremedy
ointment05.jpg&imgrefurl=http://en.heilkraeuter.net/ointment/rescue]
2.2) FORMULATION
The row materials generally used for manufacturing of ointments
a) Drug
b) Base
c) Preservative
d) Antioxidants
e) Chelating agents
f) Perfumes
a) Drug: - Drug is the active pharmaceutical ingredient which produced desired therapeutic action.
b) Ointment Bases
The ointment base is that substance or part of an ointment, which serves as carrier or vehicle for the
medicament. The nature of a base also controls its performance. Hence the selection of base is very

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important. The selection of ointment base is depending upon the action desire nature of the medicament
to be incorporated and the stability of an ointment is to be considered. [Mehta, R.M.,(1997)]
Ideal Properties of Ointments Bases
1) They should be nonirritating.
2) They should be nondehydrating.
3) They should be non grease, nonstaining.
4) They should be compatible with common medicaments.
5) They should be Stable.
6) They should be easily removable with water.
7) They are able to absorb water and/or other liquids.
8) They do not alter skin function.
9) They should be miscible with skin secretion.
10) Even phase distribution.
11) They should be nongritty.
12) They should have good texture.
13) They should have no microbial contamination.
14) They should have Smoothing and elegant properties
15) Compatible with skin secretion.
Classification of Ointment Base
Ointment bases are classified by the USP into four general groups:
i) Oleaginous bases
ii) Absorption bases
iii) Waterremovable bases
iv) Watersoluble bases [Mithal, B.M.,(1980)]
i) Oleaginous bases:
They are also termed as hydrocarbon bases.
They are not absorbed by the skin
Restricts loss of moisture and keeps the skin soft but water logging, with maceration of the skin,
if application is prolonged.
Retains body heat, which may produce an uncomfortable feeling of warmth.
They are immiscible with water
They are sticky
They are almost inert
Water absorption is low
Their constituents are readily available and cheap [Carter,S.J., (2000)]
Constituents of the hydrocarbon bases
Petrolatum is a purified mixture of semisolid hydrocarbons obtained from petroleum. It is an
unctuous mass, varying in color from yellowish to light amber. It melts at 38 to 60C and may be used
alone or in combination with other agents as an ointment base. Petrolatum is also known as yellow
petrolatum and petroleum jelly. Commercial product is Vaseline. White soft paraffin is never used in the
preparation of ophthalmic ointments because it may contain small traces of bleaching agents. It may
cause irritation to the eye. [Mehta, R.M.,(1997)],
[Ansel,Howard C.,et al., (2000)]
Hard paraffin: It is purified mixture of solid hydrocarbons. It is used to harden or soften the
ointment base.
Liquid paraffin: It is purified mixture of solid hydrocarbons and obtained from petroleum by
distillation. It is soluble in ether and chloroform but insoluble in water and alcohol. It is used along with
hard paraffin and soft paraffin to get desired consistency of the ointment.
Limitations of Oleaginous bases:-
1) Very greasy
2) They are sticky and difficult to remove from skin
3) Retain body heat
4) Not help in absorption of medicament
5) Prevent drainage on oozing areas.
ii) ABSORPTION BASES: These bases are anhydrous substances which have the property of absorbing
considerable quantity of water but still retaining their ointment like consistency.
They are mainly classified into two groups.
Nonemulsified Bases
Water in oil emulsion [Mehta, R.M.,(1997)]

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Non-emulsified Bases: These absorb water and aqueous solutions producing W/O emulsions.
Less occlusive but good emollients.
They assist oilsoluble medicaments to penetrate the skin.
They are easier to spread.
Constituents of non-emulsified bases:
Wool Fat is used in which the proportion of aqueous or hydroalcoholic liquid is too large for
incorporation in a hydrocarbon base. It is too sticky for use alone but is an important constituent of
almost half of the official ointments including simple ointment. It assists absorption of active ingredients.
Beeswax which contains small amounts of cholesterol is an ingredient of paraffin ointment. It is used
as a stiffening agent in pastes and ointments.
Wool alcohol These are the emulsifying fraction of wool fat, is a constitute of wool alcohol ointment
B.P., which contains wool alcohols and hard, liquid and white soft paraffin.
Cholesterol hydrophilic petroleum U.S.P. is an absorption ointment base. It contains cholesterol
(3%), stearyl alcohol (3%), white bees wax (8%), and white soft paraffin (86%).
Water in Oil Emulsions Bases: These are capable of absorbing more water.
Constituents of water in oil emulsion bases:
Hydrous wool fat (lanolin) is prepared from wool fat and water. It is used alone as an emollient and
is an ingredient of several ointment bases. [Carter,S.J., (2000)]
iii) Emulsion Bases (Water-Removable Bases):-
Both O/W and W/O type of emulsions have been used as bases. O/W emulsions are mainly used so these
bases are known as Water removable bases. They have cream like consistency. Because the external
phase of the emulsion is aqueous, they are easily washed from skin and often called as waterwashable
bases. They may be diluted with water or aqueous solutions. Examples are white soft paraffin and liquid
paraffin.
Certain advantages are:
Miscibility with exudates from lesions.
Reduced interference with skin functions.
Good contact with the skin.
High cosmetic acceptability. [Ansel,et al., (2000); Mehta, R.M.,(1997)]
iv) WATER-SOLUBLE BASES:
Watersoluble bases do not contain oleaginous components. They developed from the macrogols
(polyethylene glycols). The macrogols are mixtures of polycondensation products of ethylene oxide and
water. Example of polyethylene glycol 400, 3350, Macrogols 200, 300, 400. They are completely water
washable and referred as greaseless. They soften greatly with addition of water
Advantages
Water solubility: Easily removed from skin.
Good absorption by the skin: As water soluble easily penetrates through skin for the drugs which are
poorly soluble.
Good solvent properties.
Freedom from greasiness.
Compatible with many dermatological medicaments
Disadvantages
Limited uptake of water
Less bland than paraffin due to their hygroscopic nature
Reduction in activity of certain anti bacterial agents.
Solvent action on polythene and backelite, these plastics should not be used in containers or closures
for Macrogols ointments.
Other ingredients of ointment bases are
1) Vegetable oils
2) Synthetic esters of fatty acids
3) Higher fatty alcohols
4) Polar organic solvents [Carter,S.J., (2000)]
SELECTION OF DERMATOLOGICAL VEHICLES:-
There are large numbers of ointment bases which are available. There are various factors which govern
the selection of an ideal base for ointments
i) Dermatological factor
ii) Pharmaceutical factor
i) Dermatological factor

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Absorption and penetration:


Absorption means actual entry in to blood stream (systemic absorption). Penetration indicates passage
through the skin (cutaneous absorption)
The skin has three main layers, the epidermis, dermis and hypodermis. The ointment base penetrates
deep into tissues of the skin along with the medicament and which in turn allows the systemic absorption
of the medicament in to blood stream.
The animal fats (lard and wool fats) and fixed oils penetrate more readily through the skin in comparison
to mineral oils (paraffin).
Effect on skin function:
Greasy bases may interfere with the skin function like heat radiation and sweat excretion. Moreover, they
are irritated to skin. The water soluble bases and O/W emulsion provides a cooling effects.
Miscibility with skin secretions and serum:-
Skin secretions are more readily miscible with emulsion bases as compared to greasy bases. Hence drug
is more rapidly released to the skin. Due to this reason lesser proportion of the medicament is needed.
O/W emulsion bases being readily mixed with serum from broken skin are very useful for weeping
eczema.
Compatibility with skin secretions:-
Generally neutral ointment bases are preferable because they do not cause discomfort in use and are
compatible with majority of medicaments. The ointment bases should have a ph about 5.5 which is the
average ph of skin secretions.
Freedom from irritant effect:-
The ointment bases should be non irritant. Greasy bases cause irritation and may cause oedema.
Emollient properties:-
Dryness and brittleness of the skin cause discomfort to the skin. Therefore, the ointment bases should
posses emollient properties that should be able to keep the skin moist. The glycerin and propylene glycol
keep the skin moist and soft. Wool fat, lard and paraffin keep the skin soft by preventing rapid loss of
moisture from the skin.
Ease of application and removal:-
The ointment base should be easily applicable and at the same time they are easy to be removed from the
skin. Stiff and sticky bases are not suitable because they may cause damage to the newly formed tissues of
the skin.
ii) Pharmaceutical factors
Synthetic modification of the chemical structure of a drug may yield compounds with increased potency
and prolonged action of the drug.
Stability:-
The fats and oils obtained from animal and vegetable are liable to undergo oxidation. This can be
prevented by incorporating a suitable antioxidant in desired concentration. O/W emulsion bases are
liable to microbial growth and needs a proper preservative.
Solubility:-
Most of the medicament insoluble in the ointment base. Hence, for the uniform distribution, it is
necessary to mix finely powdered drug in the ointment base.
Emulsifying properties:-
Hydrocarbon bases can absorb only a small amount of water in comparison to animal fats which can
absorb large quantities of water. Example, wool fat can absorb about 50% of water, and mixed with other
fats can take up several times its own weight of water or hydro alcoholic liquids. Hence, wool fat is
included for the preparation of base meant for eye ointments.
Consistency:-
The ointment should be of suitable consistency. It should neither be too hard nor too soft. The consistency
of a base should be that it withstands wide variation in temperature condition.
Dissociation constant:-
Passage of drug (ions) is blocked by electrostatic interactions deep penetration of an ionic medicament is
influenced by its dissociation constant and ph of the surroundings.
Particle size:-
Reducing the particle size of poorly soluble drugs improves the therapeutic activity by increasing the
dissolution rate. [Mehta, R.M., (1997)], [Carter,S.J., (2000)]
c) PRESERVATIVES:-
The antimicrobial compounds are added to prevent contamination, deterioration or spoilage of ointment
base by microbes. The first consideration in selection is the irritancy or toxicity of the compound to the

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tissue to which the ointment is to be applied. Sometimes preservatives get complexed by other
ingredients and are not available in sufficient concentration. In the presence of tween 80, methyl paraben,
benzalconium chloride, benzoic acid, etc get inactivated. The bactericidal activity also depends upon
partition coefficient of the antimicrobial compound between aqueous and oily phase.
d) ANTIOXIDANT:-
These should be incorporated when there is a possibility of oxidative degradation of the base. The
concentration of antioxidant depends upon their partition coefficients between aqueous and oily phase.
Generally compounds like butylated hydroxyl anisole, propyl gallate, nor dihydroguaiaretic acid etc. are
used.
a) CHELATING AGENTS:- When traces of metallic ions are likely to catalyse oxidative degradation small
amounts of substances of such as citric acid, maleic acid, phosphoric acid may be added to chelate the
metallic ions. [Mehta, R.M.,(1997)], [Mithal, B.M.,(1980)]
b) PERFUMES:-
Most ointments have a pleasant smell imparted by incorporation of selected perfumes.
2.3) PREPARATIONS OF OINTMENT BASES:
There are mainly four methods:
By triturating
By fusion
By chemical reaction
By emulsification
By ointment mills
By Triturating: This method is used when soft fats and oil part of the base and medicament is solid
and insoluble or liquid in small amount.
Powder the solid medicament
Triturating (levigating) the ingredients in a mortar until smooth ointment is obtained.
Mortars to be preferred when much liquid is to be incorporated. [Mehta, R.M.,(1997)]
By Fusion:- when ointment base contains a number of solid ingredient of different melting point,
such as white bees wax, stearic acid, hard paraffin, it is necessary to melt them in decreasing order to
their melting point. This will avoid the overheating of the substances having low melting points. The
medicament incorporated to the melting mass with stirring. In case any aqueous substances are
incorporated, that should be heated to same temperature as base. After mixing the two portions the
stirring should be done to make a homogenous mass.
Precautions:
1) Vigorous stirring should be avoided to prevent air entrapment in the ointment.
2) Rapid cooling should be avoided to prevent separation of waxy solid from ointment [Mehta,
R.M.,(1997)]
By Chemical Reaction:
It involves both fusion and mechanical mixing.
Here new product is formed by chemical reaction
Certain hydrophilic base which involves the formation of soaps may be said to be made by chemical
reaction
E.g. Ointment containing free iodine, Ointment containing combined iodine,
By Emulsification Method:-
In this, the fat, oil, and waxes are melted together on a water bath at a temperature of 700C. The aqueous
solutions of all of the heat stable water soluble components are also heated almost at the same
temperature as that of melted bases. The solution is added to the melted mass with continuous stirring
until the product cools and ointment prepared. [Mehta, R.M.,(1997)]
By Ointment Mills
In this method, ointment is prepared by using the specific type of mill that is Triple roller mill
PRESERVATION:
Ointment contain fat and water so easily oxidisable, so add proper antioxidants
They are contaminated by micro organism and get spoiled. It can be prevented by antimicrobial
agent.
They must not react with material of container.
PACKAGING
Container:
Ointments are usually dispensed in either ointment jars or tubes
Tin and aluminum tubes are also used

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Now plastic tubes are available. [Mehta, R.M., (1997)]


2.4) EVALUTION OF BASES:-
There are two methods for evaluation of ointment base
i) Physical Methods
ii) Microbiological methods
i) Physical Methods
a) Test for Rate of Absorption: Diadermic ointments are those from which the drug moves into
deeper skin tissues and finally into the systemic circulation. Such ointments should be evaluated for the
rate of absorption of drugs. 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.
The rate of absorption i.e., the amount of drug absorbed per unit time should be more.
b) Test for Rate of Penetration
The rate of penetration of a semisolid dosage form is crucial in the onset and duration of action of the
drug. Weighed quantity of the preparation should be applied over selected area of the skin for a definite
period of time. Then the preparation left over is collected and weighed. The difference between the initial
and the final weights of the preparation gives the amount of preparation penetrated through the skin and
this when divided by the area and time period of application gives the rate of penetration of the
preparation. The test should be repeated twice or thrice. This procedure is tedious and not followed
anymore.
Using flowthrough diffusion cell or microdialysis method, the rate of penetration of the preparation can
be estimated. 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.
c) Test For Rate Release Of Drugs
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.
d) Test for 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.
e) Test for Content Uniformity
The net weight of contents of ten filled ointment containers is determined. The results should match each
other and with the labeled quantity. This test is also called minimum fill test.
[http://www.pharmainfo.net/evaluation-ointments]
f) Uniformity of weight
Ten tubes were filled randomly and weighed. Ointment was removed from each tube and each empty
tube was washed with methanol. The empty tubes were dried and their weight was taken. The difference
between two weights was calculated as net weight of the ointment of tube. The average of net weight of
ointment of ten tubes was noted.
g) pH: The pH of ointment solution was measured with the help pH meter.
h) Hardness of Ointment: It was measured by Penetrometer. Three containers were filled carefully and
completely, without forming air bubbles and stored at 25+ 0.50C for 24 hrs. Three samples were stored at
25 0.50C and with shear for 5min. Three samples were melted and carefully and completely filled three
containers, without forming air bubbles stored at 25 0.5 0C for 24 hrs. Test samples were placed on
Penetrometer. Temperature of penetrating object was adjusted at 250.50C and position was also
adjusted such that its tip just touches the surface of sample. Penetrating object was released for 5sec.
Depth of penetration was measured. Same was repeated with remaining containers10.
[http://www.ijpbs.net/issue-4/Ph-2.pdf]
ii) Microbiological Methods
a) Test of microbial content
Microorganisms like pseudomonas aeruginosa and staphylococcus aureus may contaminate the
preparation and finally infect the skin. So ointments should be tested for the absence of
Such microorganisms. 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 degrees C for 14 hours. No formation of the clot in the incubated mass indicates the absence of the
microorganisms.

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b) Test of Preservative Efficacy


Using pour plate technique the numbers of microorganisms 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 microorganisms are added into each mixture, under
aseptic conditions. All mixtures are incubated. The number of microorganisms in each sample is counted
on 7th, 14th, 21st and 28th days of inoculation.[http://www.pharmainfo.net/evaluationointments]
3) CREAMS
Creams are semisolid emulsion system with opaque appearance as contrasted with translucent ointments
and contain one or more medicinal agents dissolved or dispersed in either O/W and W/O emulsion or in
other type of water washable base. Creams are intended for application to the skin and mucous
membrane. Their consistence depends on whether the (1) emulsion is water in oil or oil in water and on
the (2) nature of solids in internal phase.
1) Their affectivity should be high.
2) They should give rapid onset of action
3) They should be biocompatible and biomiscible
4) Free from grittiness.
5) They should be smooth
6) They should be readily washable
7) They should be nonirritant
8) They should be nonallergic
9) They should be nontoxic
10) They should be physically and chemically stable
[http://semisolidpreparationcream.blogspot.in/2011/07/semisolid-preparation-cream.html]

Figure 2: Creams
[http://www.google.co.in/imgres?imgurl=http://botox.co/wpcontent/uploads/2011/02/skin
creams.jpg&imgrefurl=http://www.botox.co/botoxcreamsdothey]
3.1) CLASSIFICATION OF CREAMS:
All the skin creams are classified on different bases
1) According to function e.g. cleansing, foundation, massage cream, etc.
2) According to characteristic properties e.g. cold creams, vanishing creams
3) According to the nature and type of emulsion
The most widely accepted classification is based on function. According to functions the creams can be
classified as follows
1) Cleansing and cold cream
2) Foundation and vanishing creams
3) Night and massage creams
4) Hand and body creams
5) All purpose and general creams [Mithal, B.M. (2000)]
3.1.1) CLEANSING AND COLD CREAMS
Cleansing cream or lotion is required for removal of facial make up, surface grime, oil, and water and oil
soluble soil efficiently, mainly from the face and throat. It also removes applied cosmetics such as face
powder, rouge, foundation bases, cake makeup and lipstick.
Ease of application is an important feature of the cleansing cream and so most of the creams are liquids so
that excess creams and soil are then easily removal with tissue. The resultant layer left on the skin must
not be occlusive but should be sufficient emollient to prevent drying.
A good cleansing cream should have the following characteristics:

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It should effectively be able to remove oil soluble and watersoluble soil and surface oil from the skin,
specifically face and throat.
As a cosmetic it should be stable and have a good appearance.
It should melt or soften on application to the skin
It should spread easily without too much drag. During application, it should not feel greasy or oily.
After evaporation of any water, the cream should not become viscous.
A light emollient film should remain on the skin after use of the cream.
Types of cleansing creams
i) Beeswax borax type
ii) Liquefying Cleansing creams
i) Beeswax borax type: They liquefy on application to the skin and spread with ease. They are O/W
type of emulsion. After the creams are rubbed on the skin, a sufficient quantity of water evaporates to
impart a phase inversion to the W/O type. The solvent action of the oil, as external phase, imparts the
cleansing properly.
Formula of beeswax borax cream
Mineral oil 28.0 gm
Isopropyl myristate 14.0 gm
Acetoglyceride 2.5 gm
Petroleum jelly 7.5 gm
Beeswax 15.0 gm
Borax 1.0 gm
Water 32.0 gm
Preservative q.s.
Perfume q.s
ii) Liquefying Cleansing cream: - They are translucent liquefying anhydrous cream of thixotropic
character.
Formula of Liquefying Cleansing creams:
Mineral oil 80.0 gm
Petroleum jelly 15.0 gm
Ozokerite wax 5.0 gm
Preservative q.s.
Perfume q.s.
3.1.2) VANISHING CREAMS
They are called vanishing creams because they seem to disappear when rubbed into the skin. These are
stearic acid based and part of stearic acid saponified with the alkali and rest of the stearic acid is
emulsified with the soap in a large quantity of water.
Formula of Vanishing cream
Stearic acid 20.0 gm
Cetyl alcohol 0.50 gm
Triethanolamine 1.20 gm
Sodium hydroxide 0.36 gm
Glycerin 8.00 gm
Water 69.94 gm
Perfume q.s.
Preservative q.s
3.1.3) FOUNDATION CREAMS
Foundation creams are applied to provide a smooth emollient base or foundation before the application
of the power and other make up preparations. They help the powder to adhere to the skin due to
possession of good holding power.
Foundation creams are of two types
Pigmented creams
Unpigmented creams
Formula of foundation creams
1. Lanolin 2.00 gm
Cetyl alcohol 0.50 gm
Stearic acid 10.00 gm
Potassium hydroxide 0.40 gm
2. Propylene glycol 8.00 gm
Water 79.10 gm

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Perfume q.s.
Preservative q.s

3.1.4) NIGHT AND MASSAGE CREAMS:


Skin nourishment is important and required to provide the normal characters of the skin or as a
treatment for dry skin. To supplement foods for the skin and to treat the dry skin various creams
containing different ingredients are used. Common features are that they are generally applied on the
skin and left for several hours, say overnight. They are easy to apply but not easy to rub in because of
presence of oil/wax it is sticky and greasy.
As normally these creams are applied at night time, the time normally assigned to skin preservation and
feeding, they are called night creams. These preparations are used to supplement hormones or vitamins
to the skin and they may be termed as hormone creams or vitamin creams respectively.
Formula of night and massage creams
Mineral oil 38.0 gm
Petroleum Jelly 8.0 gm
White beeswax 15.0 gm
Paraffin wax 1.0 gm
Lanolin 2.0 gm
Borax 1.0 gm
Water 35.0 gm
Perfume q.s.
Preservative q.s.
Antioxidant q.s.
Formula of Vitamin Cream:
1. Mineral Oil 40.0 gm
Beeswax yellow 15.0 gm
Lanolin 0.5 gm
Isopropyl myristate 5.0 gm
Acetylated lanolin 0.5 gm
Concentrated solution of
Vitamin A & D 1.0 gm
2. Borax 1.0 gm
Water 37.0 gm
Perfume q.s.
Preservative q.s.
Antioxidant q.s.
Hormone Cream:
1. Acetylated lanolin 15.0 gm
Isopropyl myristate 3.0 gm
Mineral oil (heavy) 4.0 gm
Hormone (in vehicle) 1.0 gm
Beeswax 7.0 gm
Cetyl alcohol 3.0 gm
Stearyl alcohol 3.0 gm
Emulsifying agent (o/w type) 15.0 gm

2. Water 49.0 gm
Perfume q.s.
Preservative q.s.
Antioxidant q.s.
3.1.5) HAND AND BODY CREAMS:
Softness of the skin is very important and also wanted. Sebum, a substance which is secreted from the
skin, acts as a natural lubricant and keeps the skin soft and conditioned. The film produced by secreted
sebum also helps to keep the skin wet by preventing the evaporation of moisture. The repeated or
constant contact with soap and detergent does the damage or causes removal of the film sebum.
Frequent removal of this sebum makes the skin dry, scaly and less protective against infection and lead to
dermatitis. A protection required to maintain the skin in normal condition. So, hand and body creams are
used. These preparations can be liquid creams, solid creams, lotions, jellies or non aqueous types.
The main function of hand and body creams are expected to be

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Replace water loss or reduce the water loss from the surface of the skin.
Provide an oily film to protect the skin
Keep the skin soft, smooth but not greasy
Easy to apply
Formula of hand and body creams
1. Stearic acid 15.0gm
Isopropyl myristate 2.0gm
KOH 1.0gm
2. Sorbitol solution 18.3gm
Water 63.7gm
Perfume q.s.
Preservative q.s.
3.1.6) ALL PURPOSE CREAMS:-
They are also known as sports creams as they were used by sport men. They are oily and non greasy type
and can easily spread on the skin to give protective film. They are nourishing cream, or protective cream
for prevention or alleviation of sunburn, for the treatment of roughened skin areas.
Manufacturing of creams:
The total ingredients can be classified in to oil phase and aqueous phase.
Ingredients of oil phase should be mixed gradually in increasing melting order, starting with lowest
melting point substances.
Components of aqueous phase should be mixed together and warmed to about same temperature of
oil phase and mix with oil phase with continuous stirring until a smooth cream is formed.
Add perfume after cooling and mill further through roller mill
Formula of all purpose creams
Wool alcohol 2.5 gm
Microcrystalline wax 6.0 gm
Mineral oil 21.0 gm
Petroleum jelly 5.0 gm
Glycerin 5.0 gm
Magnesium sulphate 0.7 gm
Water 59.8 gm
Perfume q.s.
Methyl parahydroxybenzoate q.s.
Propyl parahydroxybenzoate q.s. [Mithal, B.M. (2000)]
3.2) FORMULATION OF CREAMS:
Solvents: various fat solvents are used in preparation of cream such as acetone, chloroform, glycerol,
kerosene, white gasoline, dioxane, 95% ethanol.
Humectants: Humectants are agents which control the moisture exchange between the product and
air, both in the jar and on the skin.
Glycerol, polyhydric alcohol, like ethylene glycol, propylene glucol solution of sodium lactate, glucose,
fructose. Various synthetic humectants are furyl glycerine, allantoin, fruit and vegetable extract etc
Spreading agents: fatty acid esters, acetylated glycerides
Emollient agents: Emollients are the most important ingredients of skin softening. Agent which are used
as emollient are lanoline, cetyl alcohol, spermaceti and cocoa butter
Opacifyin agents (2%):zinc oxide, titanium di oxide. Magnesium stearete, zinc stearate, hydrous
lanoline
Thixotropic agents: wax (paraffin)
Wax and oils: vegetable oils, fatty acid esters, mineral oil, petrolatum. The proportion of mineral oil and
wax is very important to avoid separation, sweating, and granular appearance.
Neutralizing agents: These agents mainly neutralize free fatty acid by the use of alkali. Example:
potassium hydroxide, tryethanolamine.
Pearlescent agents: They provide conditioning to the skin like liquid paraffin, spermaceti, cocoa butter,
starch, almond oil.
Hydrating agents: vegetable and fruit extract bamboo extract
Nourishing agent: vitamins , vitamin A, D ,E, F are used and various hormones are also used. Examples
are estrogen, progestin, pregnenolone and androgen. They show limited restorative effects on aged skin.
The hormones may be absorbed and produce side effects. To prevent this, the concentration of hormones
used should be very less and a suitable vehicle is required to dissolve hormone.

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Gelling agents (Thickening agents):- These are hydrophilic substances used to increase the viscisity.
Examples are tragacanth, starch, pectin, gelatin, etc
Emulsifiers:- They reduce the surface tension for proper emulsification and prevent coalescence. They
are effective at low concentration. Eg. Cetyl pyridinium chloride, Alkyl dimethyl benzyl ammonium
chloride.
Film formers:- These prevent the evaporation of water from the surface of skin. Examples are carboxy
cellulose poly vinyl alcohol.
Healing agents: The inclusion of healing agents in creams is justified because of the severe chapping
accompanied by cracking of the epidermis. These cracks are often painful. Agents that act as skin healers
urea, uric acid.
Antioxidents: They prevent oxidation are butylated hydroxyl arisol
Preservatives:- They protect the cream from microbial contamination. Examples are methyl
parahydroxy benzoate, propyl parahydroxy benzoate.
Perfumes: All creams have a pleasant smell imparted by incorporation of selected perfumes like
geranium, bois the rose, ylang yalng, lavendrol oils, linalool.
Coloring agents: These are added ao impert a colour effect according to the need.
Red (Pink) : FD&C Red No. 1, D&C Red No. 19, D&C Red No. 33. Blue : FD&C Blue No. 1, D&C Blue No. 4.
Yellow: FD&C Yellow No. 5, D&C Yellow No. 6. Green : D&C Green No. 5. . [Mithal, B.M. (2000)]
3.3) EVALUATION OF CREAMS
Generally tests like quantitative and qualitative determination of ingredients. Some others tests are
important.
Methods of Evaluation:-
a) Rheology test
b) Determination of PH
c) Sensitivity test (Patch Test)
d) Photo Patch test.
e) Peroxide Stability test
f) Test for thermal stability
g) Irritancy test
h) Drug Content Uniformity
a) Rheology Test :
Rhealogy is very2 important as these creams are marketed in tube or containers. The rheology or
viscosity should remain constant. As these products are normally nonNewtonian in nature, the viscosity
can be measured using viscometers used for such liquids.
Procedure:- The formulated cream was found to be non Newtonian. Take a fixed quantity 10gms of
cream in a 10ml beaker. Keep it impact for 1 hr. The beaker was inclined to one side see whether the
cream is liquefied or not. beaker is shaken to and fro for continuous 5mins and checked whether
consistency has changed or not. The beaker was again tilted and checked for pourability of the cream. The
formulation showed no thixotropic (shear thinning) characteristics. [http://www.ijppsjournal.com/
Vol3Suppl2/396.pdf]
b) Determination Of PH
Weigh accurately 5 0.01gm of the cream in 100ml beaker. Add 45 ml of water and disperse the cream in
it. Determine the pH of suspension at 270C using the pH meter.
[www.ijbs.net/issue-3/86.pdf]
c) Sensitivity Test (Patch Test) :-
As various types of ingredients are used with occasional use of Antiseptic hormones etc. there is a
possibility of sensitization or photosensitization of the skin.
Sensitivity testing of cosmetics may perform as diagnostic patch test. It is intended to discover. Whether
the cosmetic used has caused dermatitis.
Procedure of Patch Test:-
Place about 0.1 0.3 g of cosmetic to be tested on a piece of cotton fabric or flannel (23 Sq. cm. in size)
and apply this to the Skin of arms, thighs or back. This patch is covered with a patch of cellophane (about
5 sq. cm) and sealed with adhesive plaster (about 40 Sq. cm). Apply more then one patches at a time
control patches should also applied which is of similar cream of other brand available in market and
known not to cause any harm to the Skin. These patches are allowed to remain on the Skin for 2472
hours. If there are no reaction.
The Same patch may be reapplied fill
(a) Either a reaction is produced.
(b) On the investigator is confirmed that no reaction will occur.

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i) Photopatch test:-
Some substances are not harmful by themselves but they become harmful when exposed to sunlight so
photo patch test is necessary. For this test two patches of testing cream are prepared as in patch test and
one is exposed to sunlight for 30 minutes. This sits acts as control after further 24 hours the patch are
removed and examined. It the patch not expose to light and the Skin are exposed to light does not show
reaction nut the patch site. This has been exposed to light shows reaction. The Substance may be taken as
nonphototoxic.
j) Peroxide Stability Test:-
The test for peroxide stability can be carried out by placing about 1 gram cream in a test tube and heating
it in a constant temperature bath. Upper surface of the cream should be in level with the fluid of the bath.
The tube is kept in the constant temperature bath for 24 hours at 95oC. The contents of tube are
transferred to a 250 ml flask and peroxide contents determined.
Stability of peroxide in cream can be found out be initial concentration of hydrogen peroxide in cream
can be found out by initial concentration of hydrogen peroxide in cream and by final concentration of
hydrogen peroxide in cream after above
Mentioned treatment from the following formula.
Final H2 O2 Concentration
% Stability X 100
Initial H2 O2 Concentration
Stability of peroxide cream should be better than 95 %
Procedure of Peroxide Stability Test:-
Place about 1 gm accurately weighed sample in a 250 ml flask and add 10 ml. Chloroform to dissolve fats.
Add 50 ml of water, 15 ml dilute hydrochloride acid and about 1 gram of potassium iodide. Add three
drops of ammonia molybate solution. The Solution will turn dark due to liberation of iodine. Titrate with
0.1 sodium thiosulphate using starch as indicator. (End Point: Blue to colourless solution)
k) Test For Thermal Stability :-
Apparatus:
1) A humidity chamber/incubator controlled at 60 to 70 percent relative humidity and41oC
1) Clear glass bottles of around 30 ml capacities with plug and screw on cap for proper closure.
Procedure:-
The help of spatula insert the cream into bottle and tap it to settle to the bottom.
Fill up to two third capacity of bottle and insert plug and tighten the cap
Keep the filled bottle erect in side the incubator at 45 + 1oC for 48 hr.
The sample shall be taken to have passed the test, If an removal from the incubator shows no oil
separation or any other phase separation.
l) Irritancy Test
Mark an area (1sq.cm) on the left hand dorsal surface. The cream was applied to the specified area and
time was noted. Irritancy, erythma, edema, was checked if any for regular intervals up to 24 hrs and
reported. [http://www.ijppsjournal.com/Vol3Suppl2/396.pdf]
m) Drug Content Uniformity
The formulation equivalent to 50 mg of drug was taken and dissolved in small quantity of methanol. Then
the formulation is warmed on the water bath so that the drug present in the formulation was completely
dissolved. Then the solution is filtered through Whattman filter paper in to 50ml vol. flask. The volume is
made up to the mark which gives concentration of 1000mcg/ml. From this different concentration of
solution was taken in 10ml volumetric flask and volume was made up to 10ml with methanol and
Absorbance was measured by UV spectrophotometer at 231.6nm against blank. [www.ijbs.net/issue
3/86.pdf]
4) MATHEMATICAL TREATMENT OF ABSORPTION OF OINTMENT AND CREAM THROUGH SKIN
The extent and rate of drug absorption is influenced by various factors including skin physiology,
physicochemical properties of drugs and excipients, as well as fabrication and design of the delivery
systems.
Both topical and transdermal drug products are intended for external use. However, topical dermatologic
products are intended for localized action on one or more layers of the skin.[http://inetce.com/articles
/pdf/22114604054H01.pdf]
Skin structure: The skin can be considered to have four distinct layers of tissue.
i) Nonviable epidermis (stratum corneum)
ii) Viable epidermis
iii) dermis
iv) Subcutaneous connective tissue (hypodermis)

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i) Non-viable epidermis (stratum corneum)


The stratum corneum is the outermost desquamating horny layer of skin, comprising about 1020 cells
of flat, partially desiccated, dead, keratinized epidermal cells. Depending upon the region of the body, the
thickness of this layer ranges from 1020 m, with the thickest layer on the palms of the hands and soles
of the feet. Of the various skin layers, it is the stratum corneum that is the ratelimiting barrier to
percutaneous drug transport. In fact, the stratum corneum is a remarkably more formidable barrier to
drug transport than the epithelial barriers of gastrointestinal, nasal, buccal, vaginal, or rectal delivery
routes.
ii) Viable epidermis
This layer of the skin resides between the stratum corneum and the dermis and has a thickness ranging
from 50 100 m. The structure of the cells in the viable epidermis is physiochemically similar to other
living tissues. Cells are held together by tonofibrils.The density of this region is not much different than
water. The water content is about 90%.
iii) Dermis
Just beneath the viable epidermis is the dermis. It is a structural fibrin and very few cells are like it can be
found histologically in normal tissue. Dermis thickness range from 2000 to 3000 m and consists of a
matrix of loose connective tissue composed of fibrous protein embedded in an amorphous ground
substance.
iv) Subcutaneous connective tissue
The subcutaneous tissue or hypodermis is not actually considered a true part of the structured connective
tissue is composed of loose textured, white, fibrous connective tissue containing blood and lymph vessels,
secretory pores of the sweat gland and cutaneous nerves. Most investigators consider drug permeating
through the skin enter the circulatory system before reaching the hypodermis, although the fatty tissue
could serve as a depot of the drug (Shembale, 2010).

Figure 3:- Structure of human skin [http://www.wikimedia.org/wikipedia/commons/3/34/skin.jpg,


(February2011)]
4.1) ABSORPTION OF DRUG:-
Dermal (percutaneous, skin) absorption is describes that the transport of chemicals from the outer
surface of the skin to the systemic circulation. This is often divided into:
Penetration, which is the entry of a substance into a particular layer or structure, such as the entrance
of a compound into the stratum corneum;
Permeation, which is the penetration through one layer into a second layer that is both functionally
and structurally different from the first layer; and
Resorption, which is the uptake of a substance into the skin lymph and local vascular system and in
most cases will lead to entry into the systemic circulation (systemic absorption).
Transport of hydrophilic or charged molecules is especially difficult attributable to the lipidrich nature of
the stratum corneum and its low water content; this layer is composed of about 40% lipids, 40% protein,
and only 20% water. Transport of lipophilic drug molecules is facilitated by their dissolution into
intercellular lipids around the cells of the stratum corneum.. [http://inetce.com/articles/pdf/221146
04054H01.pdf]

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Factors influencing Absorption of Drugs


1. Drug release from dosage form
2. Drug concentration in the formulation
3. Drug oil/water partition coefficient
4. Drug affinity to the skin tissue
5. Surface area
6. Site of application
7. Hydration of the skin
8. Nature of the vehicle used
9. Rubbing or inuction
10. Contact period
11. Other factors [Venktasewarlu, (2000)]
Absorption can occur by diffusion via:
i) Transepidermal absorption
Transdermal absortion, through the stratum corneum.
ii) Transfollicular absoption (shunt pathway), via the hair follicle, sebaceous and sweat glands.

Figure 4:- Pathways of Transdermal Permeation (Stratum corneum, Transfollicular, Sweat gland)
[Singh V. July(2009)]
i) Transepidermal absorption:
It is now generally believed the Transepidermal pathway is principally responsible for diffusion across
the skin. The main resistance encountered along this pathway in the stratum corneum. Permeation by the
Transepidermal route first involves the partitioning into the stratum corneum. Diffusion then takes place
across this tissue. The current popular belief is that most substances diffuse across the stratum corneum
via the intercellular lipoidal route. In the other extreme of polarity, lipophilic molecules concentrate in
and diffuse with relative ease through the horny layers intercellular region. When a permeating drug
exits at the stratum corneum, it enters the wet cell mass of the epidermis and since the epidermis has no
direct blood supply, the drug is forced to diffuse across it to reach the vasculature immediately beneath.
(Jain, 1997).

Figure 5:- Routes of Penetration [Edith, (1999)]

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ii) Transfolicular (shunt pathway) absorption:


The skins appendages offer only secondary revenues for permeation. Sebaceous and eccrine glands are
the only appendages which are seriously considered as shunts bypassing the stratum corneum since
these are distributed over the entire body. Drug molecules in contact with the skin surface can penetrate
by three potential pathways: through the sweat ducts, via the hair follicles and sebaceous glands
(collectively called the shunt or appendageal route) or directly across the stratum corneum. It is proposed
that a follicular shunt route was responsible for the presteady state permeation of polar molecules and
flux of large polar molecules or ions that have difficulty diffusing across the intact stratum corneum.
However it is generally accepted that as the appendages comprise a fractional area for permeation of
approximately 0.1% their contribution to steady state flux of most drugs is minimal. This assumption has
resulted in the majority of skin penetration enhancement techniques being focused on increasing
transport across the stratum corneum rather than via the appendages. [Jain,N.K. (1997)]
Methods of Evaluation:-
i) Rheology test
j) Determination of PH
k) Sensitivity test (Patch Test)
l) Photo Patch test.
m) Peroxide Stability test
n) Test for thermal stability
o) Irritancy test
p) Drug Content Uniformity
4.2) MATHMETICAL TREATMENT OF ABSORPTION
The rate of drug transport across the stratum corneum follows Ficks Law of Diffusion. In other words, the
rate of drug absorption depends not only on its aqueous solubility, but is also directly proportional to its
oil/water partition coefficient, its concentration in the formulation vehicle, and the surface area of the
skin to which it is exposed; it is inversely proportional to the thickness of the stratum corneum.
[http://inetce.com/articles/pdf/221-146-04054H01.pdf]
Ficks first law:

J Which states that the flux (rate of transfer per unit area) of a compound (J, mass/cm2 per second) at a
given time and position is proportional to the differential concentration change C over a differential
distance x (i.e. the concentration gradient C/x).
The negative sign indicates that the net flux is in the direction of decreasing thermodynamic activity,
which can often be represented by the concentration. Ficks second law describing concentration
Within a membrane

is derived by combining a differential mass balance in a membrane with Ficks first law and, when
considering the skin, assuming that the compound does not bind, the compound is not metabolized, and
its diffusion coefficient does not vary with position or composition.
Ficks first law can be applied to describe the diffusion processes in the individual layers of the skin,
which are treated as pseudohomogeneous membranes.
For a membrane of thickness h, the flux at steady state (Jss) is
given by:
Jss = D (C1 C2) / h [Equation 1]
Where C1 and C2 are the concentrations of the chemical in the membrane at the two faces (i.e.at x = 0 and
x = h). When used to describe heterogeneous membranes like the stratum corneum, D is an effective
diffusion coefficient.
Commonly, the stratum corneum controls dermal absorption, h is the thickness of the stratum corneum,
and the concentration at x =h is zero or very small (i.e. C2 = 0, which is sometimes called sink conditions).
Also, the concentration of chemical at x = 0 is in local equilibrium with the vehicle (i.e. C1 = Km Cv, in
which Km is the pseudohomogeneous partition, or distribution, coefficient between the stratum corneum
and the vehicle and Cv is the vehicle concentration).
Under these conditions, Equation 1 becomes:
Jss = D Km Cv / h [Equation 2]

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The steadystate flux across the skin is sometimes written in terms of the permeability coefficient (Kp) as
follows:
Jss = Kp Cv [Equation 3]
Comparing Equations 2 and 3,
Kp = Km D / h [Equation 4]
Note that, although the partition coefficient Km is unitless, to be consistent with its use in Ficks law, it is
the ratio of concentrations in the stratum corneum and vehicle in units of mass/volume.
Typically, the steadystate flux Jss and the permeability coefficient Kp are assessed from an in vitro
experiment in which the donor concentration of the penetrant is maintained (more or less) constant (i.e.
infinite dose conditions), while the receiver phase provides sink conditions. Over time, the flux
approaches a steadystate value (Jss), and the cumulative amount penetrating the skin increases linearly
in time.
The slope of the linear portion of the graph of the cumulative amount penetrated as a function of time
represents the steadystate flux Jss. As indicated by Equation 3, Kp is the ratio of Jss and the vehicle
concentration Cv. The lag time (tlag) is the time intercept of the linear portion of the graph. The time
required for the permeation rate across a membrane to reach 95% of the steadystate value is
approximately 2.3 times the lag time (96% 2.4, 97% 2.5, 98% 2.8, 99% 3.2)
Thus, estimates of steadystate flux and permeability coefficients should include data only from times
greater than the time to reach steady state. Including data for times before the steady state is established
will lead to a false estimate, usually underestimate, of the permeability
Coefficient and lag time. In reality, depletion of the donor phase, the use of nonsink receptor conditions,
and a deterioration of the skin over time can occur and result in inaccuracies in steadystate flux and lag
time estimations.

Figure 6:- Illustration of the relationship between the cumulative mass penetrating
a membrane area (Mout/A) and the steadystate flux, permeability coefficient, and lag time (tlag).
The maximum flux (Jmax,ss) of a solute through a membrane occurs for a pure solid or a saturated
solution of a chemical in a vehicle when C2 = 0. At equilibrium, a saturated solution of chemical in a
vehicle will be in equilibrium with the saturated concentration of solute in the stratum corneum (Ssc).
The maximum flux Jmax,ss is therefore given by Equation 5, which is derived from Equation 1. It is to be
noted that Jmax,ss is also related to the permeability coefficient of a solute in a given vehicle Kp,v and the
solubility of the solute in that vehicle Sv.
Jmax,ss = Ssc D / h = Kp,v Sv [Equation 5]
In principle, higher than maximum fluxes can be observed in intrinsically unstable systems, such as
supersaturated solutions.

REFERENCES
1. Ansel Howard C., Et al. 2000. Pharmaceutical Dosage Forms and Drug Delivery Systems. Lippincott Williams &
Wilkins, India p.p. 244, 246
2. Carter S.J., .2000. Cooper And Gunns, Dispensing For Pharmaceutical Students. 12th Ed. CBS Publisher and
Distributors, Delhi, p.p. 192195
3. Jain, N.K. 1997. Controlled and Novel Drug Delivery. 1st ed. CBS Publishers & Distributors, pp.103110

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Yadav et al

4. K. Raopurushattam, Et al.2010. International Journal of Pharma and Biosciences, Preparation and Evaluation of
O/W Cream For Skin Psoriasis, p.p. 3 Available at < http://www.ijpbs.net/issue3/86.pdf> Accessed [2822015]
5. K.R., Vinod, Et al. (2011) International Journal of Pharmacy and Pharmaceutical Sciences, Formulation and
Evaluation of Piperine Cream A New Herbal Dimensional Approach For Vitiligo Patients, p.p.31, Available at
<http://www.ijppsjournal.com/Vol3Suppl2/396.pdf> Accessed [2822015]
6. Mehta R.M., (2003) Pharmaceutics II 2nd Ed. Vallabh Prakashan, Delhi, p.p. 152165
7. Metha Ratha, Topical and Transdermal Drug Delivery: What a Pharmacist needs to know Available at <
http://inetce.com/articles/pdf/22114604054H01.pdf> Accessed [26215]
8. Mithal B.M., Saha R.N., (2000) A Handbook of Cosmetics, Vallabh Prakashan, Delhi, p.p. 6189
9. Rajalakashmi, Et al. (2010) International Journal of Pharma and Biosciences, Formulation and Evaluation of
Clotrimazole and Ichthammol Ontment, Available at http://www.ijpbs.net/issue4/Ph2.pdf Accessed [262
2015]
10. Shembale, A.I. (2010) Useful Permeation Enhancers for Transdermal Drug Delivery: A Review. International
Journal of Pharma. Research & Development 2(5) 16.
11. Vankateswarlu, V. (2000) Fundamental of Biopharmaceutics and Pharmacokinetics. Paras Publishing
pp.5759

CONFLICT OF INTEREST : Nil


Received : 02.04.2015
Accepted : 30.04.2015

CITATION OF THIS ARTICLE


Sunil Y, Paras P, Sanjay B, Mohit S .Formulation and Evaluation of Ointment and Cream with Their Mathematical
Treatment of Absorption Through Skin: A Review. World J. Clin. Pharmacol. Microbiol.Toxicol. Vol 1 [1] 2015. 0926

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