Ointments are semisolid preparations that incorporate a lipid or hydrophobic excipient and are intended for external application to the skin or other muco-sal membranes.
Ointments
Ointments
are semisolid preparations that incorporate a lipid or hydrophobic excipient
and are intended for external application to the skin or other muco-sal
membranes. An ointment usually contains <20% water and other volatile
ingredients, such as ethanol, and >50% hydrocarbons, waxes, or polyols.
Ointments are designed to soften or melt at body temperature, spread eas-ily,
and have a smooth, nongritty feel. Ointments are typically used as (1)
emollients to make the skin more pliable, (2) protective barriers to prevent
harmful substances from coming in contact with the skin, and (3) vehicles for
hydrophobic drugs.
An
ointment base forms the body of any ointment. Ointment bases are classified
into four general groups: (1) hydrocarbon bases, (2) absorption bases, (3)
emulsion or water-removable bases, and (4) water-soluble bases (Table 23.1).
Table 23.1 Various types of ointment bases
Oily
or oleaginous bases include hydrocarbons derived from petroleum, which are
called hydrocarbon bases. These bases are anhydrous and insol-uble in water.
These bases are used for their emollient effect (to hydrate the skin) and as an
occlusive dressing. They cannot absorb or contain water. Thus, they can be
protective to water labile drugs, such as bacitracin and tetracycline. However,
they are greasy and not water washable. Thus, they can stain clothing and are
generally not preferred. Oily- or fatty-base oint-ments may have hard, soft, or
liquid paraffin bases, or mixtures of these, in such proportions as will render
an ointment to be of suitable consistency.
Common
hydrocarbon bases include the following:
· Petrolatum: It is used as a base for water-insoluble ingredients. Yellow petrolatum or petrolatum jelly, for example, Vaseline®, melts at 38°C–60°C. Decolored petrolatum is known as white petrola-tum. Petrolatum forms an occlusive film on the skin and absorbs less than 5% water under normal conditions. Wax can be incorporated to stiffen the base. For example, yellow ointment contains 5% w/w yel-low wax and 95% w/w petrolatum.
·
Liquid petrolatum, also known as
mineral oil, is a mixture of refined saturated
hydrocarbons obtained from petroleum that are liquid at room temperature. It is
used as a levigating agent to incorporate lipo-philic solids into ointments.
·
Synthetic esters are used as constituents of oleaginous
bases. These esters include glycerol monostearate, isopropyl myristate,
isopropyl palmitate, butyl stearate, and butyl palmitate.
·
Long-chain alcohols, such as cetyl alcohol and stearyl alcohol,
are sometimes also incorporated in oleaginous bases. In addition, lanolin
derivatives, such as lanolin oil and hydrogenated lanolin, are some-times used.
·
Plastibase® (ER Squibb & Co., Princeton, NJ) is a
commercially available polyethylene-base gelled mineral oil. It is useful for
the extem-poraneous preparation of ointments by cold incorporation of drugs,
thus being suitable for heat-labile compounds.
Absorption
bases contain an oleaginous material and a water-in-oil (w/o) emulsifier so
that they can absorb water to form or expand w/o emulsions. Absorption bases
are useful as emollients, although they do not provide the degree of occlusion
afforded by the oleaginous bases. Emollients are prepa-rations that soften and
soothe the skin. These preparations may be used to reduce the dryness and
scaling of skin. However, they are greasy because the external phase of the
emulsion is oily. Absorption bases are not easily removed from the skin with
water.
Absorption
bases are of two types:
1. Anhydrous bases that permit the incorporation of aqueous
solutions, resulting in the formation of w/o emulsions. These absorption bases
are anhydrous vehicles composed of a hydrocarbon base and an addi-tive. The
hydrocarbon base could be, for example, hydrophilic pet-rolatum and anhydrous
lanolin. The additive is a miscible substance with polar groups (a surfactant),
which functions as a w/o emulsifier. For example, cholesterol, lanosterol and
other sterols, acetylated ste-rols, or the partial esters of polyhydric
alcohols, such as monostearate or monooleate, can serve as additives.
2. Bases that are already w/o emulsions (emulsion bases) and
permit the incorporation of small additional quantities of aqueous solutions.
For example, lanolin and cold cream.
a. Lanolin is a w/o emulsion
that can form an occlusive film on the skin
and serve as an emollient, effectively preventing epidermal water loss. It
retards but does not completely inhibit, transepi-dermal water loss. It can
restore the water in the skin to a normal level of 10%–30%. Lanolin is a pale
yellow substance obtained from sheep wool. It is chemically a wax, consisting
of high molec-ular weight alcohols (e.g., sterols) and fatty acids. Lanolin can
absorb twice its own weight of water. It is self-emulsifying and produces
stable w/o emulsions. Lanolin is used to help prevent drying and chapping of
the skin.
b. Cold cream is a semisolid white
w/o emulsion prepared with cetyl ester
wax, white wax, mineral oil, sodium borate, and purified water. Sodium borate
combines with free fatty acids present in the waxes to form sodium salts of
fatty acids (soaps) that act as emulsifiers. Cold cream is employed as an
emollient and ointment base. For example, Eucerin cream is a w/o emulsion of
petrolatum, mineral oil, mineral wax, wool wax, alcohol, and bronopol. It
contains urea as the active ingredient and is used to help rehydrate dry, scaly
skin.
Emulsion
or water-removable bases are oil-in-water (o/w) emulsions. As these emulsion
bases have an aqueous external phase, they are water wash-able or water
removable. They are non/less greasy and occlusive than ole-aginous bases. They
can be diluted with water and have a better cosmetic appearance. Highly viscous emulsion bases are commonly
referred to as creams. These
represent the most commonly used type of ointment base. The majority of dermatologic drug products are formulated in an
emulsion or cream base.
An
emulsion base has three component parts: (a) an internal oil phase, which is
typically made of petrolatum and/or liquid petrolatum together with cetyl or
stearyl alcohol; (b) an emulsifier; and (c) an aqueous phase. Drugs can be
included in one of these phases before forming the emulsion or can be added to
the formed emulsion.
Emulsion
bases are of the following types:
·
Hydrophilic ointment
is
an o/w emulsion that uses sodium lauryl sul-fate as an emulsifying agent. It is
readily miscible with water and is easily removed from the skin. A typical
composition of hydrophilic ointment is listed in Table
23.2. In addition to these basic compo-nents, this base may also contain
preservatives to control microbial growth. The preservative(s) could be
methylparaben, propylparaben, benzyl alcohol, sorbic acid, or quaternary
ammonium compounds. The aqueous phase contains the water-soluble components of
the emulsion system, together with any additional stabilizers, antioxi-dants,
and buffers that may be necessary for drug stability and pH control.
·
Vanishing cream is an o/w emulsion
that contains a large percentage of water
as well as a humectant (e.g., sorbitol, glycerin, or propylene glycol)
Table 23.2 A typical composition of hydrophilic ointment
Table 23.3 A typical composition of vanishing cream
A typical composition of vanishing cream
is listed in Table 23.3. It is a cosmetic
product that is colorless when applied and is used as a foundation for powder
or as a cleansing or moisturizing cream. The hydrophobic stearyl alcohol
component in the formula helps to form a thin film when the water evaporates.
Water-soluble
bases absorb water to the point of solubility. They are water washable and may
be anhydrous, or contain some water. Water-soluble bases are made of carbowax
or polyethylene glycol (PEG) as the base. They are oil/lipid free and non/less
occlusive. However, they may absorb water from the skin, thus dehydrating the
skin, and may hinder percutaneous absorption.
PEGs
are water soluble, nonvolatile, stable, and do not support the growth of mold.
PEGs are polymers of oxyethylene units with different molecular weights. The
number at the end of PEGs indicates their average molecular weight. Their melting
point increases with increasing molecu-lar weight. Thus, PEGs with a molecular
weight ≤400–600 are liquid at room temperature; PEGs with a molecular weight
800–2,000 are waxy or semisolid; and PEGs with a molecular weight >2,000 are
solid at room temperature.
A
typical composition of water-soluble base is listed in Table
23.4. The ointment is a blend of water-soluble PEG that forms a
semisolid base. The base of PEGs alone is highly water soluble and does not
allow incorpora-tion of more than 5% w/w water or aqueous solution to make an
ointment. If greater quantities of water or aqueous component need to be added,
a
Table 23.4 A typical composition of water-soluble base
A water-soluble base can solubilize water-soluble drugs and some
water-insoluble drugs. The water-insoluble drugs are solubilized by the
cosolvent action of the nonaqueous hydrophilic poly-mers present in the base.
These bases are compatible with a wide variety of drugs.
Another
water-soluble base is the ointment prepared with propylene gly-col and ethanol,
which form a clear gel when mixed with 2% w/w hydroxy-propyl cellulose (HPC).
This base is commonly used as a dermatologic vehicle.
An
ointment base is chosen depending on
·
The solubility characteristics of the drug and the desired
rate of drug release. For example, hydrophilic drug incorporated in an o/w base
would be released immediately, whereas incorporation in a w/o emul-sion would
lead to slower drug release.
·
Whether the final product is intended for drug absorption by
the skin (percutaneous drug absorption) or not (topical application).
·
Typical properties of various ointment bases, such as water
washabil-ity and tendency for skin occlusion.
·
Intended usage of the ointment, for example, a cosmetic use
would require due attention to customer convenience factors such as water
washability and nonstaining on the clothing. On the other hand, usage in a
clinical setting, such as occlusive barrier on wounds that would be bandaged,
might not require such considerations.
In
addition to the active drug, ingredients in ointment preparations can include
oleaginous components, aqueous components, emulsifying agents, stiffeners,
penetration enhancers, preservatives, and antioxidants. Oleaginous ointments
may be prepared by levigation and fusion.
·
Levigation involves dispersing
and/or grinding an insoluble drug into small
particles while wet. Mixing of a base and other components over an ointment
slab using a spatula can carry it out. Components such as liquid petrolatum
serve as levigating agents by promoting the wetting of powders for
incorporation into bases. Hydrophobic oint-ments and w/o emulsions and suspensions
are typically prepared by levigation process to incorporate a powder and/or a
small quantity of water or hydrophilic component into an oil base.
·
Fusion process involves
melting components (such as paraffin, stearyl alcohol, white wax, yellow wax, and high molecular weight PEGs)
together to form a homogeneous solution. Fusion method is used when the base
contains solids that have higher melting points (e.g., waxes, cetyl alcohol, or
glyceryl monostearate). This process is employed only when the components are
stable at fusion tempera-tures. Hydrophilic o/w emulsions (such as
water-removable ointments and creams) are typically prepared by the fusion
process. The hydro-phobic components are melted together and added to the
aqueous phase/water-soluble components containing an emulsifying agent with
constant mixing until the mixture congeals.
Normally,
drug substances are in fine powered forms before being dis-persed in the
vehicle. Levigation of powders into a small portion of base may be facilitated
by the use of a melted base or a small quantity of com-patible levigation aid,
such as mineral oil or glycerin. Water-soluble salts of drugs are incorporated
by dissolving them in a small volume of water and incorporating the aqueous
solution into a compatible base.
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