Formulation and Optimization of Progesterone Microemulsion Using Simplex Lattice Mixture Design

Abstract

Progesterone (P4) is a neurosteroid hormone synthesized in both males and females, it is widely used in reproductive health and hormone replacement therapy. The aim of this study was to develop microemulsions (ME) and optimization of P4 microemulsion using a simplex lattice mixture design for enhancing the transdermal delivery of P4. Pseudo-ternary phase diagrams were generated to find the optimal ratio of the microemulsion constituents. The solubilities of P4 in different oils, surfactants, and co-surfactants were determined. The ME formulations of P4 were then prepared and optimized by simplex lattice mixture design. Each ME formulation was characterized for size, PDI, zeta potential, drug content, in vitro permeation study, and drug permeation in porcine skin. The result showed that the optimal ME formulation composed of 34.97 %w/w eugenol as the oil phase, 18.35 %w/w Labrasol® as the surfactant, 36.69 %w/w ethanol as the cosurfactant, and 10.00% w/w water containing HPβCD (1.0 M). The optimized ME showed an appropriate size of about 178 ± 42 nm with a low polydispersity index (PDI) and almost neutral charge. The drug content of the optimized ME was about 19.9 ± 0.6 %w/w. The results of in vitro permeability showed that the optimized ME formulation was significantly higher than the drug suspension. Moreover, the P4 from the optimized ME was able to be deposited in the dermis (1.07 mg) at a higher extent than in the stratum corneum (0.65 mg). In conclusion, this study explored a formulation approach to improve the transdermal permeation of P4.