Inhibition of crystallization in drug-in-adhesive-type transdermal patches.

In this study the ability of various additives to inhibit crystallization of two model drugs, captopril and levonorgestrel, in acrylate and silicone adhesives was investigated. Among the various additives tested, PVP was found to be the most effective in inhibiting the crystallization of both drugs. Incorporation of PVP in patches (PVP stabilized patches) allowed incorporation of both drugs in amounts higher than their respective saturation solubility in pure adhesives (saturated patches). Skin permeation profiles of the drugs from the patches across hairless rat skin were obtained using Franz diffusion cells. For the hydrophilic drug captopril the skin flux over the first 24h was the same for the saturated and PVP stabilized patches, but after 24h the PVP stabilized patches produced higher skin flux values. However this may be because the saturated patch was depleted of the drug after 24h. It is not clear if PVP performs as a solubilizer or a crystallization inhibitor for hydrophilic drugs. For the lipophilic drug levonorgestrel, the skin flux profile from the saturated and PVP stabilized patches was the same, suggesting that PVP acts just as a drug solubilizer and does not produce supersaturation. Copyright (c) 2010 Elsevier B.V. All rights reserved.