Optimization and Stability Assessment of Clindamycin HCl Transethosome: Exploring the Effects of Ethanol and Tween 80 Concentrations

Background: Clindamycin HCl is drug commonly used as an anti-acne in conventional topical formulations. However, effectiveness of clindamycin HCl in conventional topical formulations is limited due to poor skin penetration, whereas Propionibacterium acnes colonies in the deeper sebaceous follicle area. To overcome this limitation, transethosome emerged as an innovative drug delivery system capable of enhancing drug permeation through the skin. Objective: This study aimed to optimise clindamycin HCl transethosome formula using a 22-factorial design. Methods: The optimisation was carried out with two factors and two levels, ethanol (20% and 40%) and Tween 80 (15% and 25%), on the responses of particle size, polydispersity index, and entrapment efficiency. Transethosomes were prepared using the thin-layer hydration method. Furthermore, the optimum transethosomes were tested for stability using the ICH Q1A(R2) method. Results: The optimum formula contains 20% ethanol and 15% Tween 80. The optimum transethosome shows a particle size of 240.933 ± 1.488 nm, a polydispersity index (PDI) of 0.177 ± 0.013, and an entrapment efficiency (EE) of 89.401 ± 0.118%. The release model follows zero-order kinetics with an activation energy of 2.978758 cal/mol. The shelf life at 25°C ± 2°C / RH 60% ± 5% is 22.536 days, and at 5°C ± 3°C is 24.572 days. Conclusion: The optimum transethosomal formula of clindamycin HCl exhibited good initial physical characteristics, with  particle size below 250 nm, polydispersity index (PDI) of less than 0.3, and high entrapment efficiency (EE). However, the low shelf life indicated a need for further optimisation to achieve long-term stability.