Formulation optimization and evaluation of glycyrrhetinic acid loaded PLARosome using factorial design: In-vitro anti-ulcer activity and in silico PASS prediction

Abstract

The intention of project was to design and evaluate Glycyrrhetinic Acid PLARosomes as an antiulcer. Moreover, identify the probable mechanism of Glycyrrhetinic Acid as antiulcer activity. A 32 factorial design study was used for designing of experiment, to study interaction between independent variables and dependent variables to deriving optimum PLARosome formulation. Nine PLARosomes formulations (F1–F9) were prepared using the thin film hydration method using varying concentrations of soya lecithin and cholesterol. In addition, the formulation was subject to its characterization as particle size, zeta potential, SEM, capability of entrapping and % release of drugs. The prepared best formulations were checked for in vitro anti-ulcer model. Finally, molecular docking was performed to investigate the binding mode of H/K ​+ ​ATPase with Glycyrrhetinic acid, to get the probable mechanism. The result shows that the prepared PLARosomes of F4 batch have noted to be 87.30 ​± ​1.0863% drug entrapment efficiency, and an estimated average particle size distribution is to be 200.4 ​nm. Zeta potential for optimized batch F4 was found to be −36.3 ​mV. PLARosomes of F4 batch showed comparable in vitro anti-ulcer activity than the standard formulation. Moreover the F4 formulation is stable for 60 days as per the ICH guidelines. The docking study reveals that Glycyrrhetinic acid shows significant binding affinity towards the H/K ​+ ​ATPase which inhabit its function. The developed formulation was found to be stable and safe, and represents a promising system for ulcer.