Petrolatum is used in dermatology to lubricate, protect, heal and medicate the skin and as a vehicle for topical drugs. Petrolatum is not suited to formation of foams. It is an unctuous solid and does not flow and is not shakable per se. Addition of large amounts of propellant to try and improve its flow is not desirable in general since the resultant material can have a cooling effect on application to the skin, mucosal cavity or body cavity. Addition of hydrophobic solvents can be useful to improve healing qualities of the formulation and to soften the petrolatum, but it can also significantly and substantially complicate or impede foam formation.
Foams are complex multi-ingredient systems which do not form under all circumstances. High quality foams are not at all easy to produce especially in a waterless environment. Yet, foams are easy to apply, use and spread and are a preferred mode of topical application. Changes in foam composition, such as, by the addition of active ingredients, may destabilize the foam. There is, therefore, a need for a foam composition, which provides desirable properties to the skin or body cavity and can be stable whilst accommodating a variety of active ingredients.
Petrolatum in its various forms has a number of useful attributes for use in topical foamable pharmaceutical and cosmetic compositions. They are inherently stable and inert, which are clearly desirable characteristics. They are also able to moisturize and soften the skin and in appropriate amounts can act as a protective or barrier layer and can form a barrier to water, which can, for example, solubilize or cause destabilization of some active ingredients. By careful design and appropriate formulation of petrolatum compositions they can act to improve drug delivery to the skin; provide a protective environment for the drug and yet remain resistant to being washed off unintentionally. On the other hand petrolatums are by their nature greasy materials and can present a difficult challenge to formulate them into a topical non-aqueous or substantially so foamable composition that can deliver substantially uniform and stable foam that ameliorates and or overcomes the look and feel of a greasy material. It is further a problem to incorporate into such a vehicle pharmaceutically effective amounts of one or more active pharmaceutical ingredients such that they are uniformly present throughout the formulation and are effectively delivered especially without the use of an alcohol in the formulation.
Aliphatic alcohols in foam compositions promote fast drying and thereby attempt to address the sticky feeling left by many topical formulations after application; however, alcohols, and in particular short chain alcohols like methyl, ethyl and isopropyl alcohols are defatting agents and may cause skin to become dry and cracked. Also, the presence of such alcohols generates alcoholic foam that is thermal sensitive and quick breaking, e.g., it collapses readily upon contact with a surface upon exposure to body temperature environment. Although certain compositions based on petrolatum are known they are, for example, designed to form an occlusive layer in the presence of active pharmaceutical agents that are not soluble in the water or oil phase. Although some lipophillic compositions containing petrolatum and silicone oil are known, the silicone oil is an essential and main component and it is used to try and overcome the greasy feeling of petrolatum. Silicones can have substantial disadvantages in foamable compositions and foams especially in significant levels.
In the light of the unctuous, greasy, tacky, and heavy nature of petrolatum, there are problems in producing stable emulsion foams of good quality and texture from high levels of petrolatum and there is a real technical challenge of achieving inter alia a good bubble structure, texture, spreadability and look and feel. The presence of water is important in contributing to feel of the foam. Developing foams with such characteristics that are substantially free of water is a technical and inventive challenge. This challenge is increased where the formulations are to be substantially free of silicone oil and substantially free of lower alcohols.
Alcohol is known to impair the integrity of the skin barrier, dry the skin and cause skin irritation. The incidence skin irritation (burning, itching and stinging) can be very high. Thus, while alcohol is useful in solubilizing an active agent and enabling effective dermal penetration of an active agent, the development of a safe foam vehicle, which will overcome the evident skin drying and irritation caused by alcohol, is warranted, especially where sensitive skin, mucosa, or body cavity membranes are being targeted. Furthermore, foam compositions that possess a lesser degree of thermal sensitivity, thus being more useful for the treatment of large skin areas are desired.
Foamable compositions that produce foams, which are soft are desirable especially with improved stability.
It is particularly advantageous to have a foamable vehicle that is suitable for use as a base for delivery of not merely one type of active pharmaceutical ingredient (API) but is adaptable for use with one or more API's from a wide range of different types of API's with relatively minimal or minor adjustment to the vehicle. For example, by altering the amount of a component or by the addition of a buffer that provides a pH at which the API is stable as would be appreciated by a person skilled in the art.