APPLICATION OF QUALITY BY DESIGN (QBD) APPROACH IN FORMULATION OF AZITHROMYCIN LIPOSOMES FOR LOCALIZED TREATMENT OF BACTERIAL INFECTIONS

Praduman Kumar* and Amit Jain

ABSTRACT

The objective of the present investigation was to formulate liposomes of azithromycin using quality by design (QbD) approach and evaluate the formulation for various parameters. A D-optimal experiment design with two independent and two dependent variables was used to optimize the formulation with the best QTPP. Phospholipid (Lecithin) concentration, lecithin to stearyl alcohol molar ratio were selected as the critical parameters affecting the desired CQAs. Multilamellar vesicles (MLVs) were generated using a technique based on the established film method using lecithin and stearyl alcohol as the lipid components. The effect of lecithin concentration and the ratio of lecithin to stearyl alcohol was statistically validated using ANOVA and the 2 factorial model depicted a significant F-value of 38.35 for entrapment efficiency. The model presented a regression coefficient value of 0.9901 and adequate precision value of 17.302. The particles of the optimized liposome were found to be having an average particle size of 163.2 nm with a poly dispersity index of 0.391 and a zeta potential of -20.4 mV. The entrapment efficiency was found to be 72.79 ± 0.793 % (n=3). The in vitro release showed that the optimal liposomal formulation released only 82.77 ± 0.8098 % azithromycin after 48 h. The formulation was subjected to stability analysis for 28 days and the amount of azithormycin retained in the formulation was considered as the stability indicator. It was seen that around 0.8 % drug was lost in the 28 days of keeping the formulation.

Keywords: Quality by Design, Azithromycin, stability, liposome, anti-bacterial.