Ointments and their bases
Ointments are semisolid preparations that incorporate a lipid or hydrophobic excipient and are intended for external application to the skin or other mucosal membranes. An ointment usually contains less than 20% water and other volatile ingredients, such as ethanol, and greater than 50% hydrocarbons, waxes, or polyols. Ointments are designed to soften or melt at body temperature, spread easily, 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.
Types of ointment bases
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
Oily or oleaginous bases include hydrocarbons derived from petroleum, which are called hydrocarbon bases. These bases are anhydrous and insoluble 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 ointments 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 petrolatum. 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 yellow 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 lipophilic 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 sometimes used.
• Plastibase® (ER Squibb & Co., Princeton, NJ) is a commercially available polyethylene-base gelled mineral oil. It is useful for the extemporaneous 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 preparations 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 additive. The hydrocarbon base could be, for example, hydrophilic petrolatum 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 sterols, 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, transepidermal 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 molecular 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
Emulsion or water-removable bases are oil-in-water (o/w) emulsions. As these emulsion bases have an aqueous external phase, they are water washable or water removable. They are non/less greasy and occlusive than oleaginous 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 sulfate as an emulsifying agent. It is readily miscible with water and is easily removed from the skin.
In addition to these basic components, 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, antioxidants, 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) that retards surface evaporation of water. 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 molecular weight.
Selection of an ointment base
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 emulsion 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 washability 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 non-staining 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.