Abstract

The invention provides methods and means for enhancing the epidermal, transdermal and dermal permeation of a topically applied pharmacologically active agent (e.g., a drug or medicament) which has a low rate of skin penetration in the absence of a permeation enhancer and which is unstable and degrades during long-term storage with particular permeation enhancers. Also provided by the invention are methods and means to increase the skin penetration of a pharmacologically active agent which has a normally low rate of skin permeation and causes the instability and degradation of a permeation enhancer with which it is combined over a long period of time. Provided by the invention are at least one first composition containing a drug, a pharmaceutically acceptable salt, chemical derivative or formulation thereof, in a dermatologically acceptable vehicle, and at least one second composition containing a permeation enhancer in an acceptable vehicle. The compositions are physically separated until application to a body or skin surface and are topically applied, either at the same time, or sequentially within a short time of each other, and mixed or blended to form a final active composition, preferably on the skin. In addition, a premixture of the compositions can be made and applied to the skin in accordance with the invention. The invention allows a therapeutically effective amount of drug to be delivered into the skin and systemic circulation and provides significant enhancement of a drug's otherwise low level of skin permeation by the action of permeation enhancer in the active composition at the point of use.