TAGUCHI DESIGN-ASSISTED OPTIMIZATION OF CLINDAMYCIN PHOSPHATE LIPOSOMAL GEL FOR ENHANCED TOPICAL DELIVERY IN ACNE
TL;DR
The QbD-optimized clindamycin phosphate liposomal gel demonstrated favorable physicochemical characteristics, high drug entrapment, controlled drug release during the investigated 6-h period, and satisfactory physical stability during 3 months of accelerated storage.
Abstract
Objectives: The objectives of the study are to develop and optimize a clindamycin phosphate-loaded liposomal gel using a quality by design (QbD) approach for topical drug delivery in the management of acne vulgaris. Methods: Clindamycin phosphate-loaded liposomes were prepared by the thin-film hydration method using Phospholipon® 90G, selected for its high phosphatidylcholine content, excellent biocompatibility, superior vesicle-forming ability, and cholesterol. A Taguchi L9 experimental design was employed to optimize the formulation based on entrapment efficiency and vesicle size. The optimized liposomes were incorporated into a Carbopol® 940 gel and evaluated for physicochemical characteristics, in vitro drug release, release kinetics, and accelerated stability. Results: The optimized formulation (F9) exhibited an entrapment efficiency of 88.0±1.1%, a vesicle size of 140.0 nm, a polydispersity index of 0.312, and a zeta potential of −32.7 mV, indicating good colloidal stability. Fourier transform infrared and differential scanning calorimetry analyses confirmed successful drug encapsulation and compatibility between the drug and formulation excipients. The liposomal gel achieved 98.2±0.8% cumulative drug release during the 6-h experimental period. Among the kinetic models evaluated, the Higuchi model exhibited the highest correlation coefficient (R²=0.992) within the investigated release period, suggesting diffusion-governed release under the experimental conditions. Accelerated stability studies conducted for 3 months showed no significant changes in physicochemical characteristics or drug content, demonstrating satisfactory physical stability under accelerated storage conditions. Conclusion: The QbD-optimized clindamycin phosphate liposomal gel demonstrated favorable physicochemical characteristics, high drug entrapment, controlled drug release during the investigated 6-h period, and satisfactory physical stability during 3 months of accelerated storage. These findings indicate the potential of the formulation as a topical drug delivery system for acne management. However, further ex vivo skin permeation, antimicrobial activity against Cutibacterium acnes, long-term stability, and in vivo studies are required to confirm its therapeutic performance.