Composition and method for controlling drug delivery from silicone adhesive blends

Abstract

Compositions and methods for controlling transdermal drug delivery, particularly of amine-functional and basic drugs, comprising a blend of a first silicone-based polymer having a reduced silanol concentration and a second silicone-based polymer have a substantial or high silanol concentration. The blend of such silicone-based polymers, particularly pressure-sensitive silicone adhesives, provides sufficient drug solubility and reduced initial drug delivery onset to permit a prolonged delivery duration at a substantially zero-order rate of delivery.

Description

CROSS-REFERENCE TO RELATED APPLICATION [0001] This application claims the benefit of U.S. Provisional Application Ser. No. 60 / 488,928 filed Jul. 21, 2003, which is expressly incorporated by reference in its entirety.BACKGROUND OF THE INVENTION [0002] 1. Field of Invention [0003] The present invention relates to the transdermal delivery of drugs from a silicone-based polymeric mixture. More particularly the present invention relates to methods and compositions for the controlled transdermal delivery of drugs that are otherwise adversely affecting or affected by silicone-based adhesives, such as basic and amine-functional drugs. [0004] 2. Description of Related Art [0005] Delivery of certain drugs transdermally has been known to be theoretically possible for many years. However, only limited commercial exploitation of transdermal drug delivery systems has been achieved due in large part to the many practical problems to be overcome with real systems. These problems include the solubil...

AI Technical Summary

Benefits of technology

[0013] It is the object of the present invention to provide compositions and methods for delivering active agents and, in particular, amine-functional and basic drugs, that are otherwise adversely affecting or affected by silicone-based polymers in adhesive compositions of transdermal systems, that reliably prevent / inhibit crystallization of the active agent and achieve controlled and constant release rates over a pre-determined application duration, particularly for 3 days or more. These and other objects of the invention are achieved by blending a silicone-based polymer having a substantial silanol concentration with a silicone-based polymer having a reduced silanol concentration.

Problems solved by technology

However, only limited commercial exploitation of transdermal drug delivery systems has been achieved due in large part to the many practical problems to be overcome with real systems.

These problems include the solubility of the drug in the polymeric or adhesive layer, the effect of the drug on the polymeric or adhesive layer, delivery of the drug to the skin and through the stratum corneum at a constant rate over a prolonged period, and stability of the transdermal drug delivery system during storage prior to use.

However, fentanyl and other amine-functional drugs including, for example nitroglycerin, scopolamine, clonidine, nicotine, tetracain, ramipril and enalapril, that are desirable to be delivered transdermally can interact with silicone adhesives by acting as catalysts for the condensation of silicone-bonded hydroxyl groups (thereby resulting in loss of cohesivity and adhesivity) or be degraded / destabilized in the presence of such hydroxy groups.

RE 35,474 teaches that amine-functional drugs interfere with the properties of pressure-sensitive adhesives by catalyzing the reaction of silicone-bonded hydroxyl (silanol) groups and, thereby, cause increased increase shear of the pressure-sensitive adhesive material and, thus, loss of tack during storage.

RE 35,474 may result in a silanol content that is too low, and therefore an adhesive that is plasticized and oozy.

However, in formulating a simplified drug-in-adhesive transdermal system (i.e., wherein the adhesive functions as both the drug carrier and means of attachment to the topical application site), incorporating fentanyl directly into an amine compatible silicone pressure-sensitive adhesive results in crystallization of the drug and therefore loss of bioavailability.

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