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.

Background: A capsaicin cream was formulated by optimizing the rheological stability, the release behavior of the drug, and the pharmacological effect. Objectives: This study aimed to: (a) apply the Design of Experiment approach to study the rheological stability and release behaviors of a drug (capsaicin) from a formulated oil-in-water cream and (b) investigate the skin irritation and anti-inflammatory and analgesic effects of the optimized cream. Methods: The cream prepared by the emulsification method was optimized using the central composite design, and then the pharmacological effect in experimental animals was determined using Complete Freund's adjuvant (CFA). Results: The effects of a permeation enhancer (X-1), Vaseline (X-2), and surfactants (X-3) on the fluctuation of the ratio of the viscous modulus (G') to elastic modulus (G') (tan delta) after three cycles of cooling-heating (10-40 degrees C), flux, and skin deposition of capsaicin after 8 h on mouse skin were statistically analyzed and optimized. The final obtained CAP-cream did not cause irritation in the rabbit model and produced comparable anti-inflammatory and analgesic effects to the reference product (Voltaren (R) emulgel). Conclusion: This study successfully integrated the DoE approach, rheological science, and pharmacological studies to develop a stable and highly effective semi-solid product containing capsaicin.