Formulation and Evaluation of Valproic Acid Microemulsions for Enhanced Transfollicular Delivery in Guinea Pig Skin

Valproic acid (VPA) is used to treat various neurological and psychiatric conditions. While oral VPA can cause hair loss, topical application has shown potential for hair regeneration. This study aimed to develop and evaluate microemulsion (ME) formulations of VPA for enhanced transfollicular delivery. VPA-loaded MEs were prepared using oleic acid, Transcutol P, Tween 80, Labrasol, and Capryol 90. The MEs were characterized for physicochemical properties, stability, in vitro release, and ex vivo permeation through the hairy abdominal and nonhairy ear skin of guinea pigs. Eight stable ME formulations were developed with droplet sizes ranging from 10 to 24 nm, pH 4.6 to 5.2, and viscosity 77 to 85 cps. In vitro release studies showed controlled release profiles over 24 h. Permeation studies revealed enhanced drug delivery through both follicular and nonfollicular pathways compared with aqueous VPA solution. Formulations with higher surfactant/cosurfactant ratios showed increased permeation through the follicular pathway. The ME formulations significantly enhanced VPA penetration into both epidermal and follicular pathways compared with aqueous solution. The composition of the MEs, particularly the oil content, water content, and surfactant/cosurfactant ratio, played a crucial role in determining the physicochemical properties and skin permeation parameters of VPA.