DoE-based formulation, physicochemical properties, and anti-inflammatory investigation of a topical patch preparing by partially neutralized polyacrylate-based adhesive hydrogel

초록

A capsaicin patch was formulated by optimizing the adhesion, the release behavior of the patch, and the pharmacological effect. The aims of study were to 1) apply the design of experiments approach for investigating the simultaneous effect of Viscomate (partially neutralized polyacrylate)-based adhesive, glycerin plasticizing excipient and permeation enhancers on patch adhesion, and the permeation rate of model drug (capsaicin) and then 2) compare the optimal formulation with the reference product (Wellpatch (R), Metholatum, U.S.A.) in terms of pharmacological effect. The topical patch was prepared by casting the drug-loaded adhesive hydrogel on the backing layer. The adhesive ability of patches was determined by testing a 90 degrees peel rig on a texture analyzer, and the permeation rate of capsaicin (CAP) through mouse skin was evaluated using Franz diffusion cells. The effects of these critical factors on patch adhesion, CAP flux, and permeation enhancer interaction with the stratum corneum were analyzed using ANOVA and ATR-FTIR/skin hydration tests, respectively. Accordingly, Viscomate (adhesion excipient) and glycerin (plasticizing excipient) had a significant impact on patch adhesion (p < 0.05). Meanwhile, N-methyl pyrrolidone, the permeation enhancer, had a better permeation rate and higher hydration level of the stratum corneum than did Transcutol. The partially neutralized polyacrylate-based optimal formu-lation had a higher permeation rate of CAP, equal adhesion and comparable anti-inflammatory effects to those of the reference product which was also in agreement with the analysis of anatomical images of tissue structure and inflammatory cells. This study successfully integrated DoE method, release behavior and pharmacological research to develop a stable and highly effective topical product containing capsaicin.

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