Topical Pharmaceutical Foam Composition

Abstract

A stable topical alcohol-free aerosol foam containing one or more keratolytic agents is provided. The foam-forming formulation is an oil-in-water emulsion which contains one or more hydrofluoroalkane (HFA) propellants and one or more keratolytic agents. The keratolytic agent may be present in either phase of the emulsion or dispersed in the emulsion. The oil phase may consist at least in part of the HFA propellant. The foam is stable on the skin for at least 5 minutes at body temperature and disappears into the skin upon rubbing or after prolonged standing. The formulations may not contain additional co-solvents or non-HFA co-propellants. The formulations demonstrate reduced intensity of the odor and / or color associated with the keratolytic agent(s) as compared to conventional formulations containing keratolytic agents.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application is a continuation of U.S. patent application Ser. No. 11 / 552,457, filed Oct. 24, 2006, which claims the benefit of the priority of U.S. Ser. No. 60 / 729,788, filed Oct. 24, 2005.FIELD OF THE INVENTION[0002]This invention is generally in the field of pharmaceutical compositions, specifically pharmaceutical foam compositions containing keratolytic agents intended for topical administration.BACKGROUND OF THE INVENTION[0003]Pharmaceutical foams are pressurized dosage forms containing one or more active ingredients that, upon valve actuation, emit a fine dispersion of liquid and / or solid materials in a gaseous medium. Foam formulations are generally easier to apply, are less dense, and spread more easily than other topical dosage forms. Foams may be formulated in various ways to provide emollient or drying functions to the skin, depending on the formulation constituents. Accordingly, this delivery technology is a useful additio...

AI Technical Summary

Benefits of technology

[0014]The emulsion contains an oil phase and an aqueous, i.e. water-containing, phase. The active agent(s) may be dissolved in either phase or dispersed in the emulsion. The oil phase may contain, at least in part, the HFA propellant. The foam is stable on the skin, preferably for at least five minutes, more preferably at least twenty minutes, at body temperature, and disappears into the skin upon rubbing or after prolonged standing. The formulations demonstrate reduced intensity of the odor and / or color associated with the keratolytic agent(s) as compared to conventional formulations containing keratolytic agents.

[0015]The composition can further contain one or more pharmaceutically acceptable excipients such as surfactants, emollients, emulsifiers, pH stabilizing agents, chelating agents, humectants, stabilizers, preservatives, and combinations thereof, which may be present in the oil phase and / or the aqueous phase. The formulations contain little or no fragrances and / or odor masking agents, thus minimizing the skin sensitizing reactions that can occur due to the presence of such agents.

[0016]The inert non-flammable HFA propellant does not require the use of additional co-solvents or co-propellants. Besides their high volatility and vapor pressure, the HFA propellants have been found to provide an additional benefit in terms of reduction of apparent odor of active ingredients, such as sulfur and urea. They also mask color by the formation of stable foams; and leave depots of materials on the skin, which in practice, are less staining to linen and clothing than prior art preparations with the same active ingredients.

Problems solved by technology

However, as yet, only a few pharmaceutical foams are commercially available.

Although hydrocarbon propellants, such as propane and butane, can be used in the manufacturing of pharmaceutical foams, these propellants are not suited for human use since they are flammable.

Since replacing a component of any formulation means introducing new properties, and HFAs differ in their solvating power from CFCs and hydrocarbons, providing reproducible performance of reformulated aerosols for pharmaceutical uses represents a challenging task.

Such formulations, however, have a number of undesirable aspects.

Alcohol co-solvents can dry and irritate the skin.

U.S. Pat. No. 6,126,920 suggests that the use of alcohol co-solvents can lead to burning, itching, and irritation observed in the use of topical foam for delivering betamethasone.

Further, volatile alcohols are highly irritating to mucous membranes.

Formulations that contain volatile alcohols and / or alkanes are potential safety hazards due to the high flammability of the product.

Moreover, the flammability characteristics of the product require expensive precautions during manufacturing, and may require controlled environments for storage and for disposal of containers after use.

However, the use of high concentrations of fragrances can be problematic.

The use of fragrances in topical formulations can result in skin sensitizing reactions in which the patient develops sensitivity to the odor masking agent.

Furthermore, the presence of fragrances, which are often complex mixtures of different compounds, may result in undesirable side reactions between the fragrance and the active agent(s).