Pharmaceutics II (Phar 312)

1. Dermatologicals
1.1. Introduction
Dermatology is the branch of medicine dealing with the skin and its diseases, a unique specialty
with both medical and surgical aspects.

Dermatologicals include Anti-infectives: Gentamycin Cream 0.1%, Anti-infectives with

Corticosteroids: Hydrocortisone 1%, Neomycin 0.5% cream, Topical Corticosteroids:
Hydrocortisone Ointment, Acne and Dandruff Preparations: Isotretinoin 10mg Capsule,
Antiseptics and Disinfectants: Chlorhexidine Gluconate 1% cream, Fungicides and
Antiparasitics: Benzoic Acid 6%, Salicylic Acid 3%(Whitfield's Ointment), Psoriasis,
Seborrhea and Ichthyosis Preparations: Ketoconazole 2% shampoo, Keratolytics: Salicylic
Acid 3%, Analgesics and Anti-inflammatories: Diclofenac Sodium gel, Anaethetics:
Lignocaine HCl 2% gell.

Anatomy, physiology and functions of skin

The human skin comprises three tissue layers: the stratified, avascular, cellular epidermis, the
underlying dermis of connective tissue, and the subcutaneous fat. Hairy skin contains hair
follicles and sebaceous glands; the glabrous skin of the soles and palms produces a thick
epidermis with a compact stratum corneum, but there are no hair follicles or sebaceous glands.

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Figure 1. Simplified model of the stratum corneum, illustrating possible pathways of drug
permeation

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The epidermis
The multilayered epidermis varies in thickness, ranging from about 0.8 mm on the palms and
soles to 0.006 mm on the eyelids. The cells of the basal layer (stratum germinativum) divide and
migrate upwards to produce the stratum corneum or horny layer. Humans survive in a non-
aqueous environment because of the almost impermeable nature of this dead, dense layer, which
is crucially important in controlling the percutaneous absorption of drugs and other chemicals.
The stratum corneum may be only 10 µm thick when dry but swells several-fold in water. There
are two main types of horny layer: the pads of the palms and soles, which are adapted for weight
bearing and friction, and the remaining flexible, rather impermeable membranous layer. The
basal cell layer also includes melanocytes, which produce and distribute melanin granules to the
keratinocytes. Langerhans' cells (important in defence mechanisms operated by the immune
system) are prominent in the epidermis.

The dermis
The dermis (or corium), at 3-5 mm thick, consists of a matrix of connective tissue woven from
fibrous proteins (collagen, elastin and reticulin) that are embedded in an amorphous ground
substance of mucopolysaccharide. Nerves, blood vessels and lymphatics traverse the matrix and
skin appendages (eccrine sweat glands, apocrine glands, and pilosebaceous units) pierce it. The
dermis needs an efficient blood supply to convey nutrients, remove waste products, regulate
pressure and temperature, mobilize defence forces and contribute to skin colour. Branches from
the arterial plexus deliver blood to sweat glands, hair follicles, subcutaneous fat and the dermis
itself. This supply reaches to within 0.2 mm of the skin surface, so that it quickly absorbs and
systematically dilutes most compounds passing the epidermis. The generous blood volume in the
skin usually acts as a 'sink' for diffusing molecules reaching the capillaries, keeping penetrant
concentrations in the dermis very low, maximizing epidermal concentration gradients, and thus
promoting percutaneous absorption.

The subcutaneous tissue

The subcutaneous fat (subcutis, hypoderm) provides a mechanical cushion and a thermal barrier;
it synthesizes and stores readily available high-energy chemicals.

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The skin appendages
The eccrine sweat glands (2-5 million) produce sweat (pH 4.0-6.8) and may also secrete drugs,
proteins, antibodies and antigens. Their principal function is to aid heat control, but emotional
stress can also provoke sweating (the clammy palm syndrome).

The apocrine sweat glands develop at the pilosebaceous follicle to provide the characteristic
adult distribution in the armpit (axilla), the breast areola and the perianal region. The milky or
oily secretion may be coloured and contains proteins, lipids, lipoproteins and saccharides.
Surface bacteria metabolize this odourless liquid to produce the characteristic body smell.

Hair follicles develop over all skin except the red part of the lips, the palms and soles, and parts
of the sex organs. One or more sebaceous glands, and in some body regions an apocrine gland,
open into the follicle above the muscle that attaches the follicle to the dermoepidermal junction.
Sebaceous glands are most numerous and largest on the face, the forehead, in the ear, on the
midline of the back and on anogenital surfaces; the palms and soles usually lack them. These
holocrine glands produce sebum from cell disintegration; its principal components are
glycerides, free fatty acids, cholesterol, cholesterol esters, wax esters and squalene. Abnormal
sebaceous activity may lead to seborrhea (excess sebum), gland hyperplasia without clinical
seborrhoea, obstruction of the pilosebaceous canal (acne and comedones - whiteheads or
blackheads), and other types of dysfunction - the dyssebacias. The nails, like hair, consist of
'hard' keratin with a relatively high sulphur content, mainly as cysteine. Unlike the stratum
corneum, the nail behaves as a hydrophilic matrix with respect to its permeability.

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PERCUTANEOUS DRUG ABSORPTION
The absorption of substances from outside the skin to position beneath the skin, including
entrance in to the blood stream, is referred to as percutaneous absorption.

Of the many theories for drug penetration that have been advanced, the two most widely
accepted are:

1. Transappendageal penetration
The penetration via eccrine sweat gland and hair follicles

2. Transepidermal penetration
The unbroken epidermis constitutes the larger surface for absorption and is widely
regarded as the major, but not absorption of many compound.

Passive diffusion is recognized as the transport mechanism through the epidermis and
there is little evidence of active transport within the enviable cells of the stratum
corneum.

There are two possible routes for the trasepidermal absorption of drugs.
a) Intercellular diffusion (Between the cells)
b) Intracellular diffusion ( Transcellular, across the cells)

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 Fig. The macroroutes by which drugs penetrate the skin and examples of treatments
appropriate to disorders of the various strata

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Functions of the skin
The skin performs many varied functions but here only some aspects of its containment and
protective roles considered.

Mechanical function
The dermis provides the mechanical properties of skin, with the epidermis playing a minor part.
Skin is elastic, but once it has taken up its initial slack it extends further only with difficulty.
With age, the skin wrinkles and becomes more rigid. The thin horny layer is quite strong and
depends for its pliability on a correct balance of lipids, water-soluble hygroscopic substances (the
natural moisturizing factor - NMF) and particularly water. The tissue requires some 10-20% of
moisture to act as a plasticizer and so maintain its suppleness.

Protective function
Microbiological barrier The stratum corneum provides a microbiological barrier and the
sloughing of groups of corneocytes (squames), with their adhering microorganisms, aids the
protective mechanism. However, microbes penetrate superficial cracks and damaged stratum
corneum may allow access to the lower tissues, where infection may develop. The so called acid
mantle (produced by sebaceous and eccrine secretions, at pH 4.2-5.6) probably does not defend
the skin against bacteria via its acidity, as was once thought. However, skin glands also secrete
short-chain fatty acids that inhibit bacterial and fungal growth. Nitric oxide, produced from
nitrates in sweat, may help to prevent infections from skin pathogens, just as acidified nitrite has
an antimicrobial action in the oral and gastrointestinal tracts. Bacteria are unlikely to enter the
tiny opening of the inner duct of the eccrine gland; the entrances to the apocrine gland and the
hair follicle are much wider, and these appendages may become infected.

Chemical barrier An important function of human skin is to bar the entry of unwanted molecules
from outside while controlling the loss of water, electrolytes and other endogenous constituents.
The horny layer is very impermeable to most chemicals and usually contributes the rate-limiting
step in transdermal absorption. The intact skin is a very effective barricade because the
diffusional resistance of the horny layer is large and the permeable appendageal shunt route
provides only a small fractional area (about 0.1%).

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Radiation barrier For skin exposed to sunlight, ultraviolet light of 290-400 nm is the most
damaging. Three main acute reactions follow irradiation: erythema, pigmentation and epidermal
thickening. Ultraviolet light stimulates melanocytes to produce melanin, which partially protects
the skin. In a severe photosensitive disease such as xeroderma pigmentosum, sunlight may
induce changes even in patients whose intense racial pigmentation makes them less susceptible
to sunburn. Chronic reactions to sunlight include skin 'ageing', premalignancy and malignancy.
Sun-damaged skin may produce solar keratoses, progressing to a squamous cell carcinoma.
Bowen's disease, malignant melanoma and basal cell carcinoma may evolve.

Heat barrier and temperature regulation The stratum corneum is so thin over most body areas
that it does not effectively protect the underlying living tissues from extremes of cold and heat; it
is not an efficient heat insulator. The skin, however, is the organ primarily responsible for
maintaining the body at 37°[Link] conserve heat, the peripheral circulation shuts down to
minimize surface heat loss; shivering generates energy when chilling is severe. To lose heat,
blood vessels dilate, eccrine sweat glands pour out their dilute saline secretion, water evaporates,
and removal of the heat of vaporization cools the body.

Electrical barrier In dry skin, resistance and impedance are much higher than in other biological
tissues.

Mechanical shock An acute violent blow bruises and blisters the skin; friction may blister or
thicken the epidermis, producing callosities and corns. Accidental minor trauma to patients on
corticosteroids may severely damage their skin, when the collagen is thinned by drug overuse.

Facial expression results from one or more motions or positions of the muscles of the face.
These movements convey the emotional state of the individual to observers. Facial expressions
are a form of nonverbal communication. They are a primary means of conveying social
information among humans, but also occur in most other mammals and some other animal
species.

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 Table . Summary of functions of skin

1.2. Dermatological preparations

ATC code D Dermatologicals is a section of the Anatomical Therapeutic Chemical
Classification System, a system of alphanumeric codes developed by the WHO for the
classification of drugs and other medical products.
D Dermatologicals
D01 Antifungals for dermatological use
D02 Emollients and protectives
D03 Preparations for treatment of wounds and ulcers
D04 Antipruritics, including antihistamines, anesthetics, etc.
D05 Antipsoriatics
D06 Antibiotics and chemotherapeutics for dermatological use
D07 Corticosteroids, dermatological preparations
D08 Antiseptics and disinfectants
D09 Medicated dressings
D10 Anti-acne preparations
D11 Other dermatological preparations

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Semisolids constitute a significant proportion of pharmaceutical dosage forms. They serve as
carriers for drugs that are topically delivered by way of the skin, cornea, rectal tissue, nasal
mucosa, vagina, buccal tissue, urethral membrane, and external ear lining. Because of their
peculiar rheological behavior, semisolids can adhere to the application surface for sufficiently
long periods before they are washed off. This property helps prolong drug delivery at the
application site. A semisolid dosage form is advantageous in terms of its easy application, rapid
formulation, and ability to topically deliver a wide variety of drug molecules.

Semisolids are available as a wide range of dosage forms, each having unique characteristics:
ointments, creams, gels, pastes,…
Ideal Properties:
Smooth Texture
Elegant In Appearance
Non Dehydrating
Non Gritty
Non Greasy And Non Staining
Non Hygroscopic
Non Irritating
Do Not Interfere With Skin Functioning
Miscible With Skin Secretion
Have Low Sensitization Index
Easily Applicable, & Easily washability
Stable Under Various Conditions

Ointments
Ointments are greasy, semisolid preparations, often anhydrous and containing dissolved or
dispersed medicaments intended for topical application.
Ointments can be classified as:
■ Medicated ointment : contain one or more medicaments which are dissolved, dispersed or
emulsified in the base.

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They are classified according to their use:
 Acne treatment : Resorcinol, sulphur
 Antibiotics: Batracin,chlorotetracycline and neomycin
 Antifungal agents: Benzoic acid, salicylic acid
 Anti-inflammatory agents: Bethamethasone, Hydrocoritisone
 Antipruritis : Benzocain,coal tar
 Keratolytics : Resorcinol,salicylic acid and sulphur

■ Non-medicated ointment : Being commonly referred to as ointment bases and used as:

• Emollient or lubricating effect

• Used as a vehicles in the preparation of medicated ointments.

Ointment bases
Substance/part of ointment which serve as a carrier/vehicle for the medicament

Charactersticss of of Ideal base

Ointment base should be :
 Inert
 Stable
 Smooth
 Compatible with skin
 Non- irritant
 Release the medicament uniformly.

N.B But, there is no base which is ideal

Factors governing the selection of an ideal ointment base

1. Dermatological factors
Absorption and penetration
Effect on the skin

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 Miscibility with skin secretion
Compatibility with skin secretion
Non-irritant
Easily removal
Emollient property
Patient skin condition ( old, baby and young

2. Pharmaceutical factors
Stability
Solvent property
Consistency ( It should not be too hard or soft )
Types of ointment base
 Hydrocarbon bases
 Absorption bases
 Water- miscible bases
 Water- soluble bases

Hydrocarbon bases (Oleaginous)

These bases are immiscible with water and are not absorbed by the skin. They are almost inert
and absorb very little water a formulation of from skin exudates. However, they inhibit water
loss from the skin by forming a waterproof film and by improving hydration, may encourage
absorption of the medicaments through the skin.

The constituents of hydrocarbon bases

 Soft paraffin ( Petrolatum )
This is a purified mixture of semi-solid hydrocarbons from petroleum or heavy
lubricating oil.
Two types of soft paraffin
1. Yellow
2. White

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Both have a melting point range of 38-560C although there may be some batch variation in
properties. Pharmaceutically, the white form is used for products with colorless; white or pale
ingredients and yellow form for products with dark-colored ingredients.

Hard paraffin
This is a mixture of solid hydrocarbon obtained from petroleum or shale oil. It is a
colourless or white, odourless, translucent, wax-like substance that feels slightly greasy
and often appears to have a ‘crystalline’ structure.
It solidifies between 500C and 570C and used to stiffen ointment bases.

Liquid paraffin
This is a mixture of liquid hydrocarbons obtained from petroleum.
It is a transparent,colourless, almost odourless oily liquid. On long storage it is liable to
oxidation with production of peroxides and therefore it may require an antioxidant. E.g.
Tocopherol
Liquid paraffin is used to soften ointment bases and to reduce the viscosity of creams.

Paraffin substitute
A soft ointment base is produced by dissolving polythene ( [Link] 21000 ) in liquid
paraffin with the aid of heat and cooling the resulting solution rapidly to form a gel.

Polythene ([Link] 21000) + Liquid paraffin Heat Paraffin substitute

Absorption bases
Absorption bases, unlike the hydrocarbone types, are hydrophilic and, therefore, can absorb
considerable amounts of water or aqueous solutions.
They fall in to :
A) Non- emulsified : These bases absorb water and aqueous solutions
to produce water-in- oil ( W/O ) emulsions.
Compared with the hydrocarbone bases:-
 They are less occlusive but, nevertheless, are good emollients

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 They assist oil-soluble medicaments to penetrate the skin
 They are easier to spread.

The constituents include

i) Wool fat (anhydrous lanolin)
This is a type of wax 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 in to a
hydrocarbon base.

It is too sticky to use alone, but it is the most important constituent of most official ointment.

Wool fat is a major constituent of Simple Ointment B.P and Eye Ointment B.P

Simple ointment B.P

Hard paraffin ……50g
Cetosteryl alcohol..50g
Wool fat………….50g
Soft paraffin……..850g

Eye Ointment B.P

Liquid paraffin…..100g
Wool fat…………100g
Yellow soft paraffin……850 g

ii) Wool alcohols: This is the emulsifying fraction of wool fat used in wool alcohol
ointment B.P

iii) Beeswax and cholesterol: Bees wax and cholesterol are included in some
ointment base to increase water-absorbing power

B) Water- in-oil Emulsions

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 These are similar in properties to the previous group and are capable of absorbing water.
Absorption bases are less occlusive than the hydrocarbon bases and easier to spread.
They are good emollients.
The example of water in oil emulsion
Hydrous wool fat ( lanolin )
Lanolin is prepared from wool fat (70%) and water (30%)
It is used alone as an emollient and is an ingredient of several B.P.C ointment bases, i,e –
Hydrous wool fat ointment
- Calamine and coal tar ointment
- Methylsalicylate ointment

Water-miscible bases ( Water-removable bases)

In spite of their hydrophilic nature, absorption bases are rather difficult to wash from the skin
b/s although, under suitable conditions, they can emulsify a large quantity of water ,they are
miscible bases are easily removed after use.

They can be applied to scalp and other hairy regions.

There are 3 official anhydrous water-miscible bases.
1. Emulsifying ointment B.P – anionic
2. Cetrimide emulsifying ointment B.P – Cationic
3. Cetomacrogol emulsifying B.P- Non-ionic
Advantages of water-miscible bases
 Miscibility with exudates from lesions
 Reduced interference with skin function
 Good contact with skin, b/s of their surfactant content
 High cosmetic acceptability; hence there is less likelihood of the patient
discontinuing treatment
 Easy removal from the hair, skin and cloth.

N.B. Ointments with hydrocarbon or absorption bases are not very suitable for scalp conditions
because their removal is unpleasant and difficult.

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Water- soluble bases
Completely water-soluble bases have been developed from the Macrogols (Polyethylene
glycols), a range of compounds with the general formula:-

CH2OH.(CH2OCH2)n.CH2OH

Polyethylene glycols are polymers of ethylene oxide and water

polycondensation
C2H4O + H2O Poyethylene glycol ( Macrogol )
The chain length may be varied to achieve polymers having desired viscosity and physical form.
 Macrogols 200,300 ,400 Viscous liquids
 Macrogol 1500 Semi-solid
 Macrogols 6000 waxy solids
Advantages of water- soluble bases
Water solubility
 Easily removal from the skin
 Readily miscible with tissue exudates
Good absorption by the skin
 This is valuable when drugs are required to penetrate the skin
Good solvent properties
 For some water soluble dermatological e.g. Hydrocortisone
Freedom from greasiness
Satisfactory ageing properties
 They don’t hydrolyze, rancidity or support microbial growth but,
because of the hygroscopic nature of the lower molecular weight
compound.
Compatibility with many dermatological medicaments
e.g. Ammoniated mercury
Yellow mercuric oxide

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Disadvantages of water-soluble bases
Limited uptake of water
Less bland than paraffins, possibly due to their hygroscopic nature.
Reduction in activity of certain antimicrobial agents, due to hydrolysis
Solvent action on polythene and bakelite; these plastics should not be used in containers
or closures for macrogol ointments
Other ingredients of ointment base
1. Vegetable oils
e.g. Arachis ,castor, coconut and olive oils
These oils are used as emollients and softening agents
Disadvantages: Prone to oxidation requiring the inclusion of antioxidants, stabilizers
which may cause sensitization in some patients.

[Link] esters of fatty acids

Ester such as isopropyl myriatate, linoleate, palmitate and palmitate-
stearate are more consistent in composition than the vegetable oils
and are more resistant to oxidation.
 Used as substitutes for the vegetable oils in ointment base

3. Higher fatty alcohols

Examples: Cetyl,stearyl and cetostearyl alcohols
Higher fatty alcohols are used in ointment bases b/s:
 They have good emollient properties but are not greasy;they are used to improve the
emolliency of hydrocarbon baes.
 They facilitate incorporation of [Link] soft paraffin containing 5% of Cetyl alcohol
absorbs 40-50% of its weight of water and even more if 10% of wool fat is also
incorporated. they assist absorption of water by macrogol bases.
 They are readily absorbed by the skin and donot rancidify.

[Link]
Dimethicones or dimethyl polysiloxanes are used in barrier ointments to protect the

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 skin against water-soluble irritants.

5. Polar organic solvents

They are used to disperse small quantities of active medicament though a relatively
large quantity of ointment base.
Other additives for ointments and pastes
Antioxidants
The antioxidants that are used in ointment bases are similar to those listed for emulsion
( Butylated hydroxyanisole (BHA)),Butylated hydroxytolnene (BHT), and ethyl,propyl or
dodecyl gallates.

Chelating agents such as ethylendiaminetetra-acetic acid (EDTA) may also be used.

The antioxidants chosen must be compatible with medicaments incorporated in to the
base.

Preservatives
 Preservative may not be required in anhydrous ointments because the substrate is
generally unfavorable to the multiplication of any contaminating micro-organisms.
 Ointment with an aqueous component requires effective antimicrobial agents to prevent
the growth of organisms that may cause spoilage and pathogenecity.
 The preservative for emulsions are also suitable for hydrous ointment bases. Those used
most commonly are mixtures of hydroxybenzoate esters, sorbic acid, phenethyl alcohol,
organic mercurials and quaternary ammonium compounds.
 The effectiveness of the preservative system should be established by challenge tests with
appropriate organisms.

Preparation of ointments
A well-made ointment is:-
a). Uniform throughout, i.e. it contains no lumps of separated high melting pt
ingredient of the base.

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 b). Free from grittiness, insoluble powders are finely subdivided and large clumps of
particles are absent.
Methods of preparation must try to satisfy these criteria.

Both an a large and a small scale, ointments are prepared by two general methods.
1) Incorporation
2) Fusion
The method for particular preparation depends primarily up on the nature of ingredients.
1) Incorporation
In the incorporation method the component of the ointment are mixed together by various means
until a uniform preparation has been attained.

* Before incorporation the ingredient should be have to the finest stat.

On a small scale, as in the extemporaneous cpding of Rx,

 Mortal and pestle
 Ointment tile (Slab) and spatula ( are a large glass or porcelain plate may
be used to sub the ingredients together)

Mortar and Pestle

Used:- when large quantities of liquids are to be incorporated.
- when large quantity of ointment is to be prepared Otherwise, tile and spatula is
satisfactory due to its large surface area. On a large scale manufactured in stainless
steel tank.
Incorporation of solids:-

When preparing an ointment by spatulation, the pharmacist generally works the ointment with a
stainless steel spatula with a long, broad and periodically removes the accumulation of ointment
on the larger spatula with a smaller spatula.

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If the component of an ointment are reactive with the metal of the spatula (as for ex,phenol),
hard rubber spatula may be used.

The ointment is prepared by thoroughly rubbing and working the component together on the hard
surface with the spatula until the product is smooth and uniform.

Generally the ointment base is placed on one side of the working surface, and the powdered
components, previously reduced to fine powders and thoroughly blended in the mortal, area
placed on the other.

Then a portion of powder is mixed with a portion of the base until uniform, and the process is
repeated until all portions of the powder and base are combined.

The portions of prepared ointment are then combined and thoroughly blended by continuous &
movement of the spatula and through the combined portions of ointment.

When only a small portion of powder is to be added, it may be added in its entirely to a small
portion of ointment base.

If the quantity of active ingredient is very small you have to use levigating agent (mineral oil,
and glycerin)

After levigation, the dispersion is incorporated with the remainder of the base by spatulation or
by using the mortar and pestle.

Incorporation of liquids:-
Any liquids ingredients should be incorporated at the end of levigation.

Generally, mortal and pestle is preferred when large volumes of liquid are added is preferred
when large volumes of liquid are added than an ointment slab.

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2) Fusion
By the fusion method, all or some of the components of an ointment are combined by being
melted together and cooled with constant stirring until congested.

When ointment based contains several ingredients of different melting point; first add constituent
of high melting point and then adding in descending order of meting point.

Advantages:- Of melting in descending order of melting point

 Quicker
 Require less heat
 Avoid under heating or easily melted constituent.
Those components not melted are generally added to the congealing mixture as its is being
cooled and stirred.

Naturally, heat-labile substances and any volatile components are added last when the
temperature of the mixture is low enough not to cause decomposition and volatilization of the
component.

Many substances are added to the congealing mixture in solution, others are added as insoluble
powders generally levigated with a portion of the base.
 On a small scale; the fusion process may be conducted in a porcelain dish or glass beaker.
 On a large scale; it is generally carried out in large steam-jacketed kittles.
 Once congealed, the ointment may be passed through an ointment mill (in large-scale
manufacture) or rubbed with a spatula or in a mortar (in small scale ppn) to ensure a
uniform texture.
 Many medicated ointments and ointment bases containing such components as beeswax,
paraffin, stearyl alcohol, and high molecular weight polyethylene glycols, which do not
lend themselves well to mixture by incorporation, are prepared by fusion.
 After melting the melted ointment base should be stirred taking care, not to cause
localized cooling of high melting point constituent.
 Localized cooling can be occurred due to:-

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  Cold spatula or stirrer
 Putting the dish on cold surface
 Transferring melted base to cold dish
 If the product is granular after cooling, it has to be remelted with minimum amount of
heat and stirred gently until it sets fully.
We use fusion method when:-
 Constants are with hard consistency (high melting point components).
 The medicaments is soluble in melted base.

Difficulties encountered in preparation of ointment.

1). Danger of chemical rxn between steel spatula and some reactive ingredients.
Ex. I2 , salicylic acid, Benzoic acid………
Solution :- to minimize this problem, use bone spatula, wooden spatula or hard rubber
spatula.
2). Incorporation of aqueous solution in to hydrocarbon base.
Solution: add N of wool fat.
3). Incorporation of antibiotics sensitive to hydrolysis
Solution:- use hydrocarbon base.
Packaging and storage of ointment.
Ointments are usually packaged either:-
- Jars
- Tubes
Jars : - May be made of glass, uncolored, colored green, amber, or blue or opaque
- Made of plastic or porcelain.
Tubes:- are made of tine or pf plastic (collapsible tube)

* Ointment jars may be filled on a small scale by packaging the weighed amount of ointment in
to the jar by means of a flexible spatula and forcing the ointment down and along the sides
of the far to avoid the entrapment of air.

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 Ointments prepared by fusion may be poured directly in to the ointment jars for
congealing with in the jar. These oints. normally assume a finished look.

 In the large-scale manufacture of ointments, pressure fillers force a specified

amount of an oint in to a jar.

 Tubes are generally filled by pressure fillers from the open back and (opposite
and from the cap end) of the tube which is then closed and sealed.

 Oints prepared by fusion may be poured directly in to the tubes. On a small

scale, as in the extemporaneous filling of an oint tube mannually or with a
small scale filling machine.

 Tube-filled ointment predominate our jar-filled ointments primarily b/s they

are move convenient for the patient, with less handing and mess resulting.
Also, oints in tubes are less exposed to air and to potential contaminants and are therefore
likely to be more stable and to remain efficacious for longer periods of time than oints
packaged in jars.

 Most oints must be stored at temperature below 300c to prevent the softening
and even the liquefying of the base.
CREAMS
The term ‘cream’ in pharmacy and medicine is applied to viscous emulsion or semi-solid
emulsion preparation consisting of solutions or dispersions of one or more medicaments in
suitable base and intended for application to the skin or mucous membrane.

The term cream is widely used in pharmaceutical and cosmetic industry.

Many pts and physicians prefer creams to ointments. For one thing, they are generally easier to
spread, and, in the case of cream of the oil-in-water emulsion- , easier to remove than many
ointments.

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They are applied to the skin for:-
- Protective
- Beatifying
- Therapeutic or prophylactic purposes.
Creams may contain suitable antimicrobial or preservatives unless the medicaments or basis than
sufficient intrinsic bactericidal and fungicidal activity.

Creams are mainly two types:-

1). Water- in –oil (W/O) - oily cream
2). Oil –in-water (O/W) - aqueous cream

O/W emulsions are most useful as water-washable bases, whereas w/o emulsions are emollient
and cleansing.

Patients often prefer a w/o b/s

- Cream spreads move readily.
- Is less greasy
- Evaporating water soothes the inflamed tissue.

O/W (varnishing cream) After application of the cream the water evaporates leaving behind a
thin residue film of the stearic acid.

 for oozing or weeping surface (wound that release exudates from skin) = b/s O/W mix
oozing surface.

Vanishing cream is prepared by incorporation of significant amount of stearic acid in an oil-in-

water emulsion.

Sodium or potassium hydroxide reacts with the stearic acid to form a soap emulsifier.

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Humectants (glycerin, PEG, 7% sorbitol) are frequently added to vanishing creams and O/W
emulsions to decrease evaporation of water from the surface of the base.

Dilution of Creams

Sometimes dilutions of creams are required, care should be taken in diluting creams particularly
to prevent microbial contamination.

For duration of creams, appropriate diluent should be used and heating should be avoided during
mixing of diluents in the creams. Sometimes use of diluents may affect the stabilities of creams.

Diluted creams should be used with in two weeks of their preparation.

The stability and activity of cream may be impaired by the dilution such as:-
1) Diluent without antimicrobial agents reduces the overall concentration of the
preservatives in the preparation.
2) Sometimes creams changes O/W to W/O by the diluents property.
3) Change of pH and dilution, may cause precipitation or degradation of medicaments.
4) Choice of wrong diluents may cause poor solubility of medicaments.
5) The activity of medicaments may be reduced due to complex formation with diluents .
6) It may invert the activity of emulsifying agents.

General compounding procedure for creams

Emulsified creams are prepared by heating the components of the oily phase (usually including
the emergent) until molten and then cooling to 600c .

The component of the aqueous phase are mixed in a separate vessel and also heated to 60 0c. The
aqueous phase is then added to the oily phase at the some temperature.

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This is important and a thermometer should be used. The resulting emulsion should be stirred
until cool. Rapid cooling may result in separation of high melting points components. Excessive
aeration caused by vigorous stirring may also lead to a granular product. If necessary the
product may be homogenized after cooling.

Creams may contain one or more medicaments in solution in one or other of the phases. Finally
powdered insoluble medicaments may be dispensed in a cream base

Shelf-life of creams

Extemporaneously prepared creams should generally be given a short shelf- life unless freedom
from microorganisms can be assured. Proprietary products in original packs carry an expiry date
suggested by the manufacture, assuming a appropriate storage.
Diluted creams should be freshly prepared and should not be used for more than two weeks after
issue.

Container of Creams

- Wide-mounthed squat jars may be used for creams where the risk of contamination in
use is considered to be minimal, e.g. Oils creams. The container must be well closed
and prevent water evaporation.
- The mouth of the jar should be covered with a disc of greasproof paper.
- Collapsible metal or flexible plastic tubes are to be preferred since these reduce the
risk of contamination in use and most proprietary products are packed in tubes.

PASTES
Pastes, like ointments, are intended for external application to the skin.

They differ from ointments primarily in that they material and as a consequence are thicker and
stiffer than ointment.

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Pastes are used principally as absorbents, antiseptics protective, or to soothe broken skin
surfaces, this are often applied thickly on dressings rather than spread on the skin.

They are emollient but, because of this powder content, porous, hence, perspiration can escape.
Since, in addition, the powder absorb exudates, parts with a hydrochloride base less macerating
than ointments with similar base.

Most are unsuitable for treating scalp conditions because they are using difficult to remove from
the hair.

Pastes are prepared similarly to ointments. However, when a levigating agents is to be used to
render the powdered component smooth, a portion of the base is often used rather than a liquid
like mineral oil would soften the paste.

Because of the stiffness and absorptive qualities of pastes, they remain in place often application
with little tendency to softer and flow and therefore effectively employed to absorb secretion
from the site of application. Pastes are therefore preferred over ointment for acute lesions that
have a tendency toward crusting, vesiculation, or oozing.

GELS (JELLIES)

Gels are transparent or translucent semi-solid or solid preparations, consisting of solutions or

dispersions of one or more active ingredients in suitable hydrophilic or hydrophobic bases.

They are used for medication, lubrication and some miscellaneous application.

Medicated Jellies
Jellies contain a considerable amount of water and are particularly suitable as vehicle for water–
soluble medicaments such as local anesthetics, spermicides, and antiseptics.

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Lubricants Jellies
Lubricants for - glove
- Electrocardiograph lead ,cytoscopes
- Catheters or devices inserted in to internal organ.

Miscellaneous jellies
- Patch testing
As a vehicle for allergens applied to the skin to detect sensitivity.
- Electrocardiograph.
To reduce the electrical resistance b/n the patients slain and the
electrodes of the cardiograph, an electrode jelly may be applied.

Formulation of gels
 Gelling agent
Gelling agents are either organic hydrocolloids or hydrophilic inorganic
substance.
- Tragacanth
- Sodium alginate
- Pectin
- Starch
- Clay ( Bentonite)
 Preservatives
- Methylhydroxybenzoate
- Propylhydroxybenzoate

 Hygroscopic agents ( Humectant)

- To the want content of jellies and them prevent skin formation.
Ex. Glycerol, propylene glycol or sorbitol solution.

 Chelating agents

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 For ingredients which are sensitive to heavy metals. ex. EDTA.

Containers
Containers should be well-filled, to minimize evaporation of water into the air
space, well closed and stored in a cool place, to prevent drying out.

Liquid preparations

Liquid preparations for external application include simple soaks or baths, applications,
liniments, lotions, paints, varnishes, tinctures, and ear drops. A simple soak provides an active
ingredient in aqueous solution or suspension, sometimes with water-miscible solvents. Gums and
gelling agents may vary the consistency, from mobile liquids to stiff ringing gels. Bath additives
such as Oilatum Emollient deposit a layer of liquid paraffin on the stratum corneum in an attempt
to maintain its moisture content by occlusion. Applications may be liquid or viscous and often
incorporate parasiticides, e.g. dicophane, benzyl benzoate, gamma benzene hexachloride and
malathion. Liniments may be alcoholic or oily solutions or emulsions, which should not be
applied to broken skin. Lotions are aqueous solutions or suspensions from which water
evaporates to leave a thin uniform coating of powder. Evaporation cools and soothes the skin,
making lotions valuable for treating acutely inflamed areas. Alcohol enhances the cooling effect
and glycerol sticks the powder to the skin. Lotions may also be dilute emulsions, usually of the
oil-in-water type. Paints, varnishes and tinctures present solutions of active ingredients in volatile
solvents such as water, industrial methylated spirits, acetone or ether. Ear drops are often
aqueous solutions, although glycerol and alcohol may also be used.

LINIMENTS
Liniments are alcoholic or oleaginous solutions or emulsions of various medicinal substances
interned for external application to the skin generally with rubbing

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Alcoholic or hydroalcholic vehicle
Are useful in instances in which rubificient, counterirritants or penetrating action is desired.

Oleaginous liniments
- are employed primarily when massage is desired
- By nature oleaginous liniment are less irritating to the skin than alcoholic liniments.
- Liniments are not generally applied to skin areas that are broken or brused b/s
excessive irritation might [Link] vehicle for a liniment should therefore be selected
on the basis of the type of action desired (rubefacient, counterirritant, or just massage)
and also on the solubility of the desired components in the various solvent.
For oleaginous liniments, the solvent may be fixed oils such as almond oil, peanut oil, sesame
oil, , or cottonseed oil or a volatile substance.
[Link] are presently no official liniment.

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