Development and Stability of a New Transdermal Formulation of Pregabalin for Skin Permeation

Pregabalin is a first-line treatment for neuropathic pain, but its oral use is often limited by central nervous system side effects, which may require dose reduction or discontinuation. A transdermal formulation may help minimize this adverse effect. The aim of this study was to improve the skin permeability of pregabalin by assessing the feasibility of in-hospital preparation and evaluating its stability in the early stages of formulation development. A 0.4% pregabalin formulation was prepared using hydrophilic cream, lipophilic cream, and pluronic lecithin organogel (PLO) gel. Ex vivo skin permeation studies were conducted using Franz diffusion cells and excised dorsal skin from hairless male mice (HR-1, 7 weeks old). Samples were collected over time and analyzed by LC-tandem MS. Drug content, pH, and viscosity were assessed under 2 storage conditions (25°C/60% relative humidity [RH] and 40°C/75% RH) to evaluate stability. The hydrophilic cream showed the highest cumulative drug permeation, flux, and permeability coefficient. Penetration enhancers added to the PLO gel did not improve absorption. Drug content remained stable under 25°C/60% RH. An inverse correlation was observed between viscosity and drug permeation, suggesting that lower viscosity facilitated diffusion. pH values remained within the physiological range, indicating low irritation potential. The hydrophilic cream demonstrated superior transdermal delivery characteristics for pregabalin. These findings support its potential as an effective and safe alternative to oral administration for managing neuropathic pain.