Definition: Ointments are semisolid preparations for application to the skin or mucosae.
- The ointment bases are almost always anhydrous and generally contains one or more medicaments in suspension or solution.
Characteristics
of an ideal ointment:
1.
It should be chemically and physically stable.
2.
It should be smooth and free from grittiness.
3.
It should melt or soften at body temperature and be easily applied.
4.
The base should be non-irritant and should have no therapeutic action.
5.
The medicament should be finely divided and uniformly distributed
throughout the base.
Classification
of ointments
According to their therapeutic properties based on
penetration of skin.
(a)
Epidermic, (b) Endodermic, (c) Diadermic
(a) Epidermic
ointments
These ointments are intended to produce their action
on the surface of the skin and produce local effect.
They are not absorbed.
They acts as protectives, antiseptics and
parasiticides.
(b) Endodermic
ointments
These ointments are intended to release the
medicaments that penetrate into the skin. They are partially absorbed and acts
as emollients, stimulants and local irritants.
(c) Diadermic
ointments
These ointments are intended to release the
medicaments that pass through the skin and produce systemic effects.
OINTMENT BASES
The ointment base is that substance or part of an
ointment preparation which serves as carrier or vehicle for the medicament.
An ideal ointment base should be inert, stable,
smooth, compatible with the skin, non-irritating and should release the
incorporated medicaments readily.
Classification
of ointment bases:
1.
Oleaginous bases
2.
Absorption bases
3.
Water-miscible bases
4.
Water soluble bases
OLEAGINOUS BASES
These bases consists of oils and fats. The most
important are the
Hydrocarbons i.e. petrolatum, paraffins
and mineral oils.
The animal fat
includes lard.
The combination of these materials can produce a
product of desired melting point and viscosity.
(a) Petrolatum
(Soft paraffin)
This is a purified mixture of semi-solid
hydrocarbons obtained from petroleum or heavy lubricating oil.
Yellow soft
paraffin (Petrolatum; Petroleum jelly)
This a purified mixture of semisolid hydrocarbons
obtained from petroleum. It may contain suitable stabilizers like, antioxidants
e.g. a-tocopherol (Vitamin E), butylated hydroxy
toluene (BHT) etc.
Melting range : 38 to 560C.
White soft
paraffin (White petroleum jelly, White petrolatum)
This a purified mixture of semisolid hydrocarbons
obtained from petroleum, and wholly or partially decolorized by percolating the
yellow soft paraffin through freshly burned bone black or adsorptive clays.
Melting range : 38 to 560C.
Use: The white form is used when
the medicament is colourless, white or a pastel shade. This base is used in
Dithranol ointment B.P.
Ammoniated Mercury and Coal tar ointment B.P.C.
Zinc ointment B.P.C.
(b) Hard
paraffin (Paraffin)
This is a mixture of solid hydrocarbons obtained
from petroleum.
It is colourless or white, odorless, translucent,
wax-like substance. It solidifies between 50 and 570C and is used to
stiffen ointment bases.
(c) Liquid
paraffin (Liquid
petrolatum,; White mineral oil)
It is a mixture of liquid , hydrocarbons obtained
from petroleum. It is transparent, colourless, odourless, viscous liquid.
On long storage it may oxidize to produce peroxides
and therefore, it may contain tocopherol or BHT as antioxidants.
It is used along with hard paraffin and soft
paraffin to get a desired consistency of the ointment. Tubes for eye, rectal and
nasal ointments have nozzles with narrow orifices through which it is difficult
to expel very viscous ointments without the risk of bursting the tube. To
facilitate the extrusion upto 25% of the base may be replaced by liquid
paraffins.
Advantages of
hydrocarbons bases:
(i)
They are not absorbed by the skin. They remain on the surface as an
occlusive layer that restricts the loss of moisture hence, keeps the skin soft.
(ii)
They are sticky hence ensures prolonged contact between skin and
medicament.
(iii) They are almost inert. They
consist largely of saturated hydrocarbons, therefore, very few
incompatibilities and little tendency of rancidity are there.
(iv)
They can withstand heat sterilization, hence, sterile ophthalmic
ointments can be prepared with it.
(v)
They are readily available and cheap.
Disadvantages
of hydrocarbon bases;
(i)
It may lead to water logging followed by maceration of the skin if
applied for a prolonged period.
(ii)
It retains body heat, which may produce an uncomfortable feeling of
warmth.
(iii) They are immiscible with
water; as a result rubbing onto the surface and removal after treatment both
are difficult.
(iv)
they are sticky, hence makes application unpleasant and leads to
contamination of clothes.
(v)
Water absorption capacity is very low, hence, these bases are poor in absorbing
exudate from moist lesions.
ABSORPTION BASE
The term absorption base is used to denote the water
absorbing or emulsifying property of these bases and not to describe their
action on the skin.
These bases (some times called emulsifiable ointment bases) are generally anhydrous substances
which have the property of absorbing (emulsifying) considerable quantity of
water yet retaining its ointment-like consistency.
Preparations
of this type do not contain water as a component of their basic formula but if
water is incorporated a W/O emulsion results.
Wool Fat
(anhydrous lanolin)
It is the purified anhydrous fat like substance
obtained from the wool of sheep.
·
It is practically insoluble in water but can absorb water upto 50% of
its own weight. Therefore it is used in ointments the proportion of water or
aqueous liquids to be incorporated in hydrocarbon base is too large.
·
Due to its sticky nature it is not used alone but is used along with
other bases in the preparation of a number of ointments.
e.g. Simple ointment B.P. contains 5% and the B.P.
eye ointment base contains 10% woolfat.
Hydrous Wool
Fat (Lanolin)
·
It is a mixture of 70 % w/w wool fat and 30 % w/w purified water. It is
a w/o emulsion. Aqueous liquids can be emulsified with it.
·
It is used alone as an emollient.
·
Example:- Hydrous Wool Fat Ointment B.P.C., Calamine Coal Tar Ointment.
Wool Alcohol
It is the emulsifying fraction of wool fat. Wool alcohol is obtained from wool
fat by treating it with alkali and separating the fraction containing cholesterol
and other alcohols. It contains not less than 30% of cholesterol.
Use:-
·
It is used as an emulsifying agent for the preparation of w/o emulsions
and is used to absorb water in ointment bases.
·
It is also used to improve the texture, stability and emollient
properties of o/w emulsions.
Examples :- Wool alcohol ointment B.P. contains 6% wool
alcohol and hard, liquid and soft paraffin.
Beeswax
It is purified wax, obtained from honey comb of
bees.
It contains small amount of cholesterol. It is of two
types: (a) yellow beeswax and (b) white beeswax.
Use:-
Beeswax is used as a stiffening agent in ointment
preparations.
Examples:-Paraffin ointment B.P.C. contains beeswax.
Cholesterol
It is widely distributed in animal organisms. Wool
fat is also used as a source of cholesterol.
Use:- It is used to increase the water absorbing power
of an ointment base.
Example:- Hydrophilic petroleum U.S.P. contains:
Cholesterol
3%
Stearyl
alcohol 3%
White
beeswax 8%
White
soft paraffin 86%
Advantages of
absorption bases:
(i)
They are less occlusive
nevertheless, are good emollient.
(ii)
They assist oil soluble medicaments to penetrate the skin.
(iii) They are easier to spread.
(iv)
They are compatible with majority of the medicaments.
(v)
They are relatively heat stable.
(vi)
The base may be used in their anhydrous form or in emulsified form.
(vii) They can absorb a large
quantity of water or aqueous substances.
Disadvantages: Inspite of their
hydrophilic nature, absorption bases are difficult to wash.
WATER MISCIBLE BASES
They are miscible with an excess of water. Ointments
made from water-miscible bases are easily removed after use.
There are three official anhydrous water-miscible
ointment bases:-
Example:-
EmulsifyingointmentB.P. - contains anionic emulsifier.
Cetrimide emulsifying ointment B.P. - contains cationic emulsifier
Cetomacrogol emulsifying ointment B.P. - contains non-ionic emulsifier
Uses: they are used to prepare o/w creams and are easily
removable ointment bases
e.g. Compound Benzoic Acid Ointment (Whitfield’s Ointment) - used as antifungal ointment.
Advantages of
water miscible bases:
(i)
Readily miscible with the exudates from lesions.
(ii)
Reduced interference with normal skin function.
(iii) Good contact with the skin,
because of their surfactant content.
(iv)
High cosmetic acceptability, hence there is less likelihood of the
patients discontinuing treatment.
(v)
Easy removal from the hair.
WATER SOLUBLE BASES
Water soluble bases contain only the water soluble
ingredients and not the fats or other greasy substances, hence, they are known
as grease-less bases.
Water soluble bases consists of water soluble ingredients such as polyethylene
glycol polymers (PEG) which are popularly known as “carbowaxes” and
commercially known as “macrogols”.
They are a range of compounds with the general formula:
CH2OH
. (CH2OCH2) n CH2OH
The PEGs are mixtures of polycondensation products
of ethylene and water and they are described by numbers representing their
average molecular weights. Like the paraffin hydrocarbons they vary in
consistency from viscous liquids to waxy solids.
Example:-
Macrogols
200, 300, 400 - viscous liquids
Macrogols
1500 - greasy semi-solids
Macrogols
1540, 3000, 4000, 6000 - waxy solids.
Different PEGs are mixed to get an ointment of
desired consistency.
Advantages of PEGs as ointment base:
(a)
They are water soluble; hence, very easily can be removed from the skin
and readily miscible with tissue exudates.
(b)
Helps in good absorption by the skin.
(c)
Good solvent properties. Some water-soluble dermatological drugs, such
as salicylic acid, sulfonamides, sulfur etc. are soluble in this bases.
(d)
Non-greasy.
(e)
They do not hydrolyze, rancidify or support microbial growth.
(f)
Compatibility with many dermatological medicaments.
Disadvantages:
(a)
Limited uptake of water. Macrogols dissolve when the proportion of
water reaches about 5%.
(b)
Reduction in activity of certain antibacterial agents, e.g. phenols,
hydroxybenzoates and quaternary compounds.
(c)
Solvent action on polyethylene and bakelite containers and closures.
Certain other substances which are used as water
soluble ointment bases include tragacanth, gelatin, pectin, silica gel, sodium
alginate, cellulose derivatives, etc.
FACTORS GOVERNING SELECTION OF AN IDEAL OINTMENT
BASE
1. Dermatological factors
2. Pharmaceutical factors
1.
Dermatological factors
(a) Absorption and Penetration:
‘Penetration’ means passage of the drug across the
skin i.e. cutaneous penetration, and ‘absorption’ means passage of the drug
into blood stream.
·
Medicaments which are both soluble in oil and water are most readily absorbed
though the skin.
·
Whereas animal and vegetable fats and oils normally penetrate the skin.
·
Animals fats, e.g. lard and wool fat when combined with water,
penetrates the skin.
·
o/w emulsion bases release the medicament more readily than greasy
bases or w/o emulsion bases.
(b) Effect on the skin
·
Greasy bases interfere with normal skin functions i.e. heat radiation
and sweating. They are irritant to the skin.
·
o/w emulsion bases and other water miscible bases produce a cooling
effect due to the evaporation of water.
(c) Miscibility with skin secretion and sebum
Skin secretions are more readily miscible with
emulsion bases than with greasy bases. Due to this the drug is more rapidly and
completely released to the skin.
(d) Compatibility with skin secretions:
The bases used should be compatible with skin
secretions and should have pH about 5.5 because the average skin pH is around
5.5. Generally neutral ointment bases are preferred.
(e) Non-irritant
All bases should be highly pure and bases specially
for eye ointments should be non-irritant and free from foreign particle.
(f) Emollient properties
Dryness and brittleness of the skin causes
discomfort to the skin therefore, the bases should keep the skin moist. For
this purpose water and humectants such as glycerin, propylene glycol are used.
Ointments should prevent rapid loss of moisture from the skin.
(g) Ease of application and removal
The ointment bases should be easily applicable as
well as easily removable from the skin by simple washing with water. Stiff and
sticky ointment bases require much force to spread on the skin and during
rubbing newly formed tissues on the skin may be damaged.
2.
Pharmaceutical factors
(a) Stability
Fats and oils obtained from
animal and plant sources are prone to oxidation unless they are suitably
preserved. Due to oxidation odour comes out. This type of reactions are called rancidification. Lard, from animal
origin, rancidify rapidly. Soft paraffin, simple ointment and paraffin ointment
are inert and stable. Liquid paraffin is also stable but after prolonged
storage it gets oxidized. Therefore, an antioxidant like tocopherol (Vit -E) may be incorporated. Other antioxidants those
may be used are butylated hydroxy toluene
(BHT) or butylated hydroxy hydroxy
anisole (BHA).
(b) Solvent properties
Most of the medicaments used in the preparation of
ointments are insoluble in the ointment bases therefore, they are finely
powdered and are distributed uniformly throughout the base.
(c) Emulsifying properties
Hydrocarbon bases absorbs very small amount of
water.
Wool fat can take about 50% of water and when mixed
with other fats can take up several times its own weight of aqueous solution.
Emulsifying ointment, cetrimide emulsifying
ointment and cetomacrogol emulsifying ointment are capable of absorbing
considerable amount of water, forming w/o creams.
(d) Consistency
The ointments produced should be of suitable
consistency. They should neither be hard nor too soft. They should withstand
climatic conditions. Thus in summer they should not become too soft and in
winter not too hard to be difficult to remove from the container and spread on
the skin.
The consistency of an ointment base can be
controlled by varying the ratio of hard and liquid paraffin.
PREPARATION OF
OINTMENTS
A well-made ointment is -
(a) Uniform
throughout i.e. it contains no lumps of separated high melting point
ingredients of the base, there is no tendency for liquid constituents to
separate and insoluble powders are evenly dispersed.
(b) Free from
grittiness, i.e. insoluble powders are finely subdivided and large lumps of
particles are absent. Methods of preparation must satisfy this criteria.
Two mixing techniques are frequently used in making
ointments:
1. Fusion,
in which ingredients are melted together and stirred to ensure homogeneity.
2. Trituration,
in which finely-subdivided insoluble medicaments are evenly distributed by
grinding with a small amount of the base or one of its ingredients followed by
dilution with gradually increasing amounts of the base.
1. Ointments
prepared by Fusion method:
When an ointment base contain a number of solid
ingredients such as white beeswax, cetyl alcohol, stearyl alcohol, stearic
acid, hard paraffin, etc. as components of the base, it is required to melted
them. The melting can be done in two methods:
Method-I
The components are melted in the decreasing order of
their melting point i.e. the higher m.p. substance should be melted first, the
substances with next melting point and so on. The medicament is added slowly in
the melted ingredients and stirred thoroughly until the mass cools down and
homogeneous product is formed.
Advantages:
This will avoid over-heating of substances having
low melting point.
Method-II
All the components are taken in subdivided state and
melted together.
Advantages:
The maximum temperature reached is lower than
Method-I, and less time was taken possibly due to the solvent action of the
lower melting point substances on the rest of the ingredients.
Cautions:
(i)
Melting time is shortened by grating waxy components (i.e. beeswax,
wool alcohols, hard-paraffin, higher fatty alcohols and emulsifying waxes) by
stirring during melting and by lowering the dish as far as possible into the
water bath so that the maximum surface area is heated.
(ii)
The surface of some ingredients discolors due to oxidation e.g. wool
fats and wool alcohols and this discolored layers should be removed before use.
(iii) After melting, the
ingredients should be stirred until the ointment is cool, taking care not to
cause localized cooling, e.g. by using a cold spatula or stirrer, placing the
dish on a cold surface (e.g. a plastic bench top) or transferring to a cold
container before the ointment has fully set. If these precautions are ignored,
hard lumps may separate.
(iv)
Vigorous-stirring, after the ointment has begun to thicken, causes
excessive aeration and should be avoided.
(v)
Because of their greasy nature, many constituents of ointment bases
pickup dirt during storage, which can be seen after melting. This is removed
from the melt by allowing it to sediment and decanting the supernatant, or by
passage through muslin supported by a warm strainer. In both instances the
clarified liquid is collected in another hot basin.
(vi)
If the product is granular after cooling, due to separation of high
m.p. constituents, it should be remelted, using the minimum of heat, and again
stirred and cooled.
Example:
(i) Simple
ointment B.P. contains
Wool
fat 50g
Hard
paraffin 50g
Cetostearyl
alcohol 50g
White
soft paraffin 850g
Type of
preparation:
Absorption ointment base
Procedure:
Hard
paraffin and cetostearyl alcohol on water-bath. Wool fat and white soft
paraffin are mixed and stirred until all the ingredients are melted. If
required decanted or strained and stirred until cold and packed in suitable
container.
(ii) Paraffin
ointment base
Type of preparation:
Hydrocarbon ointment base
(iii) Wool
alcohols ointment B.P.
Type of
preparation:
Absorption base
(iv)
Emulsifying ointment B.P.
Type of
preparation:
Water-miscible ointment base.
(v) Macrogol
ointment B.P.C
Type of
preparation:
Water soluble ointment base
Formula: Macrogol 4000
Liquid
Macrogol 300
Method: Macrogol 4000 is melted and
previously warmed liquid macrogol 300 is added. Stirred until cool.
2. OINTMENT PREPARED BY TRITURATION
This method is applicable in the base or a liquid
present in small amount.
(i)
Solids are finely powdered are passed through a sieve (# 250, # 180,
#125).
(ii)
The powder is taken on an ointment-slab and triturated with a small
amount of the base. A steel spatula with long, broad blade is used. To this
additional quantities of the base are incorporated and triturated until the
medicament is mixed with the base.
(iii) Finally liquid ingredients
are incorporated. To avoid loss from splashing, a small volume of liquid is
poured into a depression in the ointment an thoroughly incorporated before more
is added in the same way. Splashing is more easily controlled in a mortar than
on a tile.
Example:
(i) Whitfield ointment (Compound benzoic acid
ointment B.P.C.)
Formula: Benzoic acid, in fine powder 6gm
Salicylic
acid, in fine powder 3gm
Emulsifying
ointment 91gm
Method: Benzoic acid and salicylic
acid are sieved through No. 180 sieves. They are mixed on the tile with small
amount of base and levigated until smooth and dilute gradually.
(ii) Salicylic acid sulphur ointment B.P.C.
3. OINTMENT PREPARATION BY CHEMICAL REACTION
Chemical reactions were involved in the preparation
of several famous ointments of the past, e.g. Strong Mercuric Nitrate Ointment,
of the 1959 B.P.C.
(a) Ointment
containing free iodine
Iodine is only slightly soluble in most fats and
oils but readily soluble.
Iodine is readily soluble in concentrated solution
of potassium iodide due to the formation of molecular complexes KI.I2,
KI.2I2, KI.3I2 etc.
These
solutions may be incorporated in absorption-type ointment bases.
e.g.
Strong Iodine Ointment B.Vet.C
(British Veterinary Pharmacopoeia) is used to treat ringworm in cattle. It
contains free iodine. At one time this type of ointments were used as
counter-irritants in the treatment of human rheumatic diseases but they were
not popular because:
They stain the skin a deep
red color.
(i)
Due to improper storage the water dries up and the iodine crystals
irritate the skin, hence glycerol was some times added to dissolve the iodine-potassium
iodide complex instead of water.
Example: Strong Iodine Ointment B.
Vet.C.
Iodine
Woolfat
Yellow
soft paraffin
Potassium
iodide
Water
Procedure:
(i)
KI is dissolved in water. I2 is dissolved in it.
(ii)
Woolfat and yellow soft paraffin are melted together over water bath.
Melted mass is cooled to about 400C.
(iii) I2 solution is
added to the melted mass in small quantities at a time with continuos stirring
until a uniform mass is obtained.
(iv)
It is cooled to room temperature and packed.
Use: - Ringworm in cattle.
(b) Ointment
containing combined iodine
Fixed oils and many vegetable and animal fats absorb
iodine which combines with the double bonds of the unsaturated constituents,
e.g.
CH3.(CH2)
2.CH = CH.(CH2) 7.COOH + I2 ® CH3.(CH2) 2.CHI
CHI.(CH2) 7.COOH
Oleic
acid di-iodostearic
acid
Example: Non-staining Iodine
Ointment B.P.C. 1968
Iodine
Arachis
Oil
Yellow
Soft Paraffin
Method:
(a)
Iodine is finely powdered in a glass mortar and required amount is
added to the oil in a glass-stoppered conical flask and stirred well.
(b)
The oil is heated at 500C in a water-bath and stirred
continually. Heating is continued until the brown color is changed to
greenish-black; this may take several hours.
(c)
From 0.1g of the preparation the amount of iodine is determined by
B.P.C. method and the amount of soft paraffin base is calculated to give the
product the required strength.
(d)
Soft paraffin is warmed to 400C. The iodized oil is added
and mixed well. No more heat is applied because this causes deposition of a
resinous substance.
(e)
The preparation is packed in a warm, wide-mouthed, amber color, glass
bottle. It is allowed to cool without further stirring.
4. PREPARATION OF OINTMENTS BY EMULSIFICATION
An emulsion system contain an oil phase, an aqueous
phase and an emulsifying agent.
For o/w emulsion systems the following emulsifying
agents are used:
(i)
water soluble soap
(ii)
cetyl alcohol
(iii)glyceryl
monostearate
(iv)
combination of emulsifiers: triethanolamine stearate + cetyl alcohol
(v)
non-ionic emulsifiers: glyceryl monostearate, glyceryl monooelate, propylene
glycol stearate
For w/o emulsion creams the following emulsifiers
are used:
(i)
polyvalent ions e.g magnesium, calcium and aluminium are used.
(ii)
combination of emulsifiers: beeswax +
divalent calcium ion
The viscosity of this type of creams prevent
coalescence of the emulsified phases and helps in stabilizing the emulsion.
Example:
Cold cream:
Procedure:
(i)
Water immiscible components e.g. oils, fats, waxes are melted together
over water bath (700C).
(ii)
Aqueous solution of all heat stable, water soluble components are
heated (700C).
(iii) Aqueous solution is slowly
added to the melted bases with continuous stirring until the product cools down
and a semi-solid mass is obtained.
N.B. The aqueous phase is heated otherwise high
melting point fats and waxes will immediately solidify on addition of cold
aqueous solution.