Transfersomal lyophilized gel of buspirone HCl: formulation, evaluation and statistical optimization

Abstract

Context: Buspirone HCl has very low oral bioavailability (4%) due to deactivation by extensive first pass effect. It also has very limited transdermal permeation due to its high hydrophilicity.Objective: The aim of this study was to increase the transdermal permeation of buspirone HCl utilizing a stable dosage form.Methods: Transfersomes were prepared using Tween-80 as a flexibility imparting agent to the vesicular walls. Oleic acid and/or ethanol, with different percentages, were utilized as a permeation enhancer. Formulations were characterized by analyzing particle size, polydispersity index, zeta potential, entrapment efficiency, in vitro release and ex vivo drug permeation. Factorial design (32) was planned for the optimization of formulations using Design-Expert® software. Lyophilized transfersomal gel of the optimized formulation was prepared using hydroxypropyl methylcellulose (HPMC) K100, carboxymethyl cellulose or sodium alginate with or without mannitol as a cryoprotectant. Physical characterization of the transfersomes and the lyophilized gel were carried out using transmission and scanning electron microscopy, respectively.Results: The optimized formulation (T7), containing 35% oleic acid, had the highest desirability value (0.658) with high ex vivo drug flux (43.40 µg/h/cm2) through rat skin when compared with the aqueous drug solution and formula T1 (without oleic acid). The T7 transfersomal gel containing HPMC K100 (G2) had the highest desirability value (0.640) among the lyophilized gel formulations with decreased ex vivo drug flux (38.98 µg/h/cm2) in comparison with the original transfersomal formula (T7).Conclusions: Lyophilized transfersomal gel containing oleic acid was considered as a promising transdermal delivery system for hydrophilic drugs.