Liposomes as an ocular delivery system of fluconazole: in-vitro studies

ABSTRACT

The purpose of this study was to formulate topically effective controlled release ophthalmic fluconazole liposomal formulations. Reverse-phase evaporation technique was used for the preparation of fluconazole liposomes consisting of phosphatidylcholine [PC] from soyabean and cholesterol [Ch] in weight ratios of [91], [72], [73], [74], [64], [76] and [55] with or without stearylamine [SA] or dicetyl phosphate [DP] as positive and negative charge inducers, respectively. The prepared liposomes were evaluated for their in-vitro release. The release mechanism was found to follow Higuchi and first order kinetics. Increasing cholesterol weight ratio in the prepared liposomal formulations progressively decreased the release of fluconazole from the vesicles. The positively charged liposomes showed slower rate of drug release compared to neutral ones. Negatively charged liposomes showed slight increase in the release rate and extent of fluconazole from the liposomal formulations 550.25 and 550.5; in comparison with neutral ones. Further increase in the amount of dicetyl phosphate 551 resulted in a significant decrease in the release rate. Four fluconazole liposome eye drops were prepared. Physical stability study including, visual appearance, particle size and amount of drug leakage from liposome eye drops were studied. Approximately 82.82%, 76.55%, and 70.90% of fluconazole was retained in negative, positive and neutral liposomal ocular formulations up to a period of 24 weeks at 5°C