Formulation and characterization of alprazolam-loaded nanoliposomes: screening of process variables and optimizing characteristics using RSM

Abstract

This research study aimed to develop a novel sustained release formulation of alprazolam that can also be used for transdermal delivery. This was carried out, for the first time, through encapsulation of alprazolam in nanoliposomes using ethanol injection. In order to obtain the best formulation, four process variables, including the solvent/nonsolvent volume ratio, phospholipid concentration, alprazolam concentration, and cholesterol content were considered as key factors. Response surface methodology (RSM) and a central composite design (CCD) model were used to investigate the effect of these factors on vesicle size (VS) and encapsulation efficiency (EE) as the major properties of nanoliposomes. Experimental data were statistically analyzed, and two significant quadratic models were developed to test the VS and EE responses. The findings indicate that alprazolam and phospholipid concentrations have a significant effect on the mean VS. However, EE was significantly affected by both the alprazolam and phospholipid concentrations and the cholesterol content. The optimized formulation for preparation of alprazolam-loaded nanoliposomes with appropriate VS and EE was suggested. Small unilamellar vesicles (SUVs), ranging in size from 50 to 100 nm were clearly observed in the transmission electron microscopy (TEM) images, which is appropriate for transdermal delivery of alprazolam. The study of the prepared nanoliposomes over 28 days at 4 °C confirmed the stability of the formulations containing cholesterol. The results of an in vitro release study of alprazolam-loaded nanoliposomes in phosphate buffered saline (PBS), pH 7.4 for 24 h at 37 °C using dialysis, indicated the sustained release of alprazolam due to encapsulation.