Preparation of Glycyrrhetinic Acid Liposomes Using Lyophilization Monophase Solution Method: Preformulation, Optimization, and In Vitro Evaluation

Abstract

In this study, glycyrrhetinic acid (GA) liposomes were successfully prepared using lyophilization monophase solution method. Preformulation studies comprised evaluation of solubility of soybean phosphatidylcholine (SPC), cholesterol, and GA in tert-butyl alcohol (TBA)/water co-solvent. The influences of TBA volume percentage on sublimation rate were investigated. GA after lyophilization using TBA/water co-solvent with different volume percentage was physicochemically characterized by DSC, XRD, and FTIR. The XRD patterns of GA show apparent amorphous nature. FTIR spectroscopy results show that no chemical structural changes occurred. Solubility studies show aqueous solubility of GA is enhanced. The optimum formulation and processing variables of 508 mg SPC, 151 mg cholesterol, 55% volume percentage of TBA, 4:1 trehalose/SPC weight ratio were obtained after investigating by means of Box-Benhnken design and selection experiment of lyoprotectant. Under the optimum conditions, satisfactory encapsulation efficiency (74.87%) and mean diameter (191 nm) of reconstituted liposomes were obtained. In vitro drug release study showed that reconstituted liposomes have sustained-release properties in two kinds of release medium. Furthermore, in vitro cell uptake study revealed that uptake process of drug-loaded liposomes by Hep G2 cells is time-dependent.