Development and optimization of besifloxacin hydrochloride loaded liposomal gel prepared by thin film hydration method using 32 full factorial design

Abstract

The objective of this present research work was to develop and optimize a liposomal gel containing a fourth generation fluoroquinolone antibiotic, besifloxacin hydrochloride (BSF−HCl), for ocular delivery using factorial design. The ocular delivery of BSF−HCl loaded liposomal gels may produce improve the ocular bioavailability with increased residence time of drug in the cornea and decreasing the non-productive absorption of besifloxacin hydrochloride. Besifloxacin hydrochloride loaded liposomes were prepared by thin-film hydration technique. The effect of two independent factors (soya lecithin to cholesterol ratio and lipid to drug ratio) on characteristics of liposomes i.e. responses (entrapment efficiency, drug loading and particle size) were examined. A quadratic polynomial model equation was generated to predict the relationship between independent factors and the responses. The in vitro drug release from the optimized liposomes exhibited biphasic release pattern for the initial rapid release and subsequently sustained drug release. The optimized liposomes (F1) were incorporated into a gel containing carbopol 940, tri-ethanolamine and glycerol. The optimized BSF−HCl loaded liposome formulation (F1) showed the encapsulation efficiency, drug loading and particle size of 41.01 ± 1.22%, 10.84 ± 0.46% and 436.8 ± 23.4 nm, respectively. The ex-vivo corneal permeation of the drug loaded liposomal gel demonstrated a significant (p < 0.05) increment of BSF−HCl permeation than the BSF−HCl loaded gel and the histological study on the pig cornea showed no corneal drainage even after 8 h of application. Thus, the developed BSF−HCl loaded liposomal gel could be used as an effective ocular drug delivery system to treat bacterial infections.