Screening of process variables using Box– Behnken design in the fabrication of berberine hydrochloride-loaded transethosomes for enhanced transdermal delivery

Abstract

Objective: The objective of the present work was to develop, optimize, and characterize berberine hydrochloride (BBN-HCl)-loaded transethosomes (TEs) for enhanced transdermal delivery. In this study, screening of formulation and process variables was conducted using Box–Behnken design approach to observe significant and insignificant influence on the TEs. Materials and Methods: The TEs was developed by homogenization technique (hot method). The optimized BBN-HCl-loaded TEs were evaluated for its vesicle size (VS), polydispersity index (PDI), zeta potential (ZP), loading capacity, and entrapment efficiency. Characterization was done by powder X-ray diffraction (P-XRD), differential scanning calorimetric (DSC), and transmission electron microscopy. Further, in vitro drug release study, stability study, and confocal laser scanning microscopy (CLSM) study were also performed. Results: The BBN-HCl-loaded TEs are developed using soya lecithin as phospholipid, oleic acid as edge activator, and cholesterol as stabilizer. Developed TEs showed acceptable desired VS (185–435 nm), excellent colloidal dispersion characteristics (PDI – 0.141–0.321 and ZP – −17.34–−24.35 mV), and high drug entrapment (67.05–85.21%). P-XRD and DSC results suggested that BBN-HCl encapsulated in amorphous state within TEs. In vitro drug release study shows prolonged release of BBN-HCl for 24 h and CLSM confirmed accumulation of TEs in deeper layers of the skin. Results of stability studies showed optimized TEs are more stable in refrigerated temperature (4°C) as compared to room temperature (25°C). Conclusion: The developed TEs successfully encapsulated berberine hydrochloride, yielding an increased permeation and deeper penetration. The results suggested that TEs could be better alternative to deliver drugs across the skin and potential carrier for efficient transdermal drug delivery.