Application of Central Composite Design for Development and Optimization of Eflornithine Hydrochloride-loaded Sustained Release Solid Lipid Microparticles

Abstract

Topical application of eflornithine hydrochloride (EFH) is the only available non-hormonal and non-systemic choice available for hirsutism treatment. EFH has low permeability (log P is -2.9). The current investigation's objective is the development of solid lipid microparticles-based sustained topical release delivery with enhanced permeability of eflornithine hydrochloride. EFH-loaded solid lipid microparticles (EFH-SLM) composed of Monecol PC and Softemul 165 using emulsion solvent evaporation technique. The central composite design has been applied to explore an optimized EFH-SLM, which was incorporated into cream (EFH-SLM-C) and evaluated for in-vitro drug release and permeation analysis. Design expert software illustrated that an optimized EFH-SLM having desirability function (0.806) could be achieved using 1:3.74 drug: lipid (w/w) (X1), 1.84% surfactant concentration (X2), and 3.5 h stirring time (X3), which would illustrate entrapment efficiency (74.97%), drug loading (15.84%), mean diameter (102.8 µm) and process yield (78.07%). EFH-SLM-C revealed biphasic fickian diffusion release of 16.95% within 0.5 h, 52.31% in the next 4 h followed by sustained release of 88.75% over 24 h. This was confirmed by release exponent 0.411 (n < 0.45) for Korsmeyer-Peppas. In-vitro steady-state flux (Jss) (µgcm-2h-1) from EFH-C and EFH-SLM-C were 17.27 and 36.65 while apparent permeability coefficient (Papp) (cmh-1) was 0.046 and 0.0977, respectively. EFH-SLM-C could be a promising strategy for augmented permeation and sustained release with minimization of dose, frequency of application, and local adverse effects.