Quality by Design (QbD) enabled and Box-Behnken design assisted approach for formulation of tranexamic acid loaded stratum corneum lipid liposomes

Tranexamic acid, a highly hydrophilic drug, is used for treatment of hyperpigmentation but topical delivery of drug is limited by poor permeation across lipidic stratum corneum membrane. Stratum corneum lipid liposomes have lipidic composition similar to that of stratum corneum layer that aids in efficient topical delivery of drugs. For quantitative analysis of drug, a LC-MS/MS based approach was successfully developed. In this study a QbD based approach was applied to optimize tranexamic acid loaded stratum corneum lipid liposomes by working on elements of QTPPs, CQAs, CMAs, CPPs and risk assessment. A 33 Box-Behnken design was used for correlation between independent variables (lipid: cholesterol ratio, RPM of magnetic stirrer and number of cycles of probe sonication) and dependent variables (encapsulation efficiency and mean particle size). A robust model was achieved, which had potential of being explored for the identification of design space. Both the responses (CQAs) were later overlayed to find the optimality region and an optimized batch was thus obtained having encapsulation of 35.78% and mean particle size of 93.5 nm. The final optimized batch as per desirability was studied further for in vitro drug release and that showed a complete release (101.65%) within 6 h that followed a zeroorder drug release kinetics. The study concludes a reliable and robust formulation model for stratum corneum lipid liposomes with reduced failure and variability. Study also focuses on encapsulation of tranexamic acid (hydrophilic drug) in lipidic carrier systems. This paper lays the groundwork for future preclinical and clinical studies of stratum corneum lipid liposomes containing tranexamic acid for topical administration.