Transdermal delivery rate control using amorphous pharmaceutical compositions

Abstract

A pharmaceutical composition for transdermal delivery comprisingone or more physiologically active agents;one or more dermal penetration enhancers; anda volatile pharmaceutically acceptable carrier comprising a volatile solvent;and wherein the physiologically active agent and dermal penetration enhancer form an amorphous deposit upon evaporation of the volatile carrier, said amorphous deposit forming a reservoir within the stratum corneum; and(A) wherein the composition has a release rate profile of physiologically active agent so as to provide a ratio of the maximum concentration (Cmax) to the average concentration (Cavg) for the physiologically active agent over the dosage interval within the range of 1 to 10.

Description

FIELD OF THE INVENTION[0001]The present invention relates to compositions for the transdermal delivery of physiologically active agents, to uses of those compositions, and to methods for the transdermal delivery of physiologically active agents.BACKGROUND OF THE INVENTION[0002]There is a constant need for methods for the safe and effective administration of physiologically active agents. For many medications it is important that the administration regime is as simple and non-invasive as possible in order to maintain a high level of compliance by a patient. Oral administration is one administration regime that is commonly used because it is a relatively simple regime to follow. However, the oral administration route is also complicated because of complications associated with gastrointestinal irritation and with drug metabolism in the liver.[0003]Administration of physiologically active agents through the skin (‘transdermal drug delivery’) has received increased attention because it ...

AI Technical Summary

Benefits of technology

This approach results in improved percutaneous absorption efficiency, reduced skin irritancy, and stability of the amorphous composition, avoiding issues like crystallization and supersaturation, with the ability to modify release rate profiles for optimal therapeutic effects.

Problems solved by technology

However, the oral administration route is also complicated because of complications associated with gastrointestinal irritation and with drug metabolism in the liver.

However, transdermal drug delivery is complicated by the fact that the skin behaves as a natural barrier and therefore transport of agents through the skin is a complex mechanism.

These existing amorphous delivery systems suffer from the particular disadvantage of being prone to poor stability during storage over their shelf-life which makes them particularly difficult to design and develop and in many instances has led to variability in drug release and / or dramatic changes in physical appearance (e.g. crystallization and supersaturation in drug-in-adhesive transdermal patch delivery systems).

These existing volatile:non-volatile delivery systems suffer from the limitations of using water soluble dermal penetration enhancers that have poor substantivity for the skin and thus are unreliable in maintaining a stable amorphous composition within the skin over the delivery period due to their propensity to wash out of the skin.

Further, these prior art systems are prone to irritate the skin due to the solvent nature of the penetration enhancers used within such prior art systems (which results in significant penetration of the enhancer into the viable epidermis).

While these methods have all aimed at improvements in percutaneous absorption none have solved the problem of forming a stable amorphous composition capable of controlling the extent and / or profile of transdermal release of a physiologically active agent from within the skin whilst avoiding the skin irritation seen with prior art systems and compositions.

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