Formulation and Characterization of Posaconazole Loaded Cubosomes For Ocular Application

Abstract

Objective: Posaconazole is a BCS class II, broad spectrum anti-fungal agent, currently used off-label for the treatment of fungal keratitis. Any ocular formulation of Posaconazole is not available in market due its low aqueous solubility, poor corneal permeation and rapid elimination from the eye. To overcome these problems present work aimed the formulation and characterization of Posaconazole loaded cubosomes (PS cubosomes) for ocular application in the management of fungal keratitis. Methods: The PS loaded cubosomes was formulated by Top to Bottom Technique by using various concentrations of GMO as lipid and Poloxamer 407 as stabilizer. Total nine formulations were prepared and one final formulation was (CB6) optimized on the basis of particle size and entrapment efficiency of PS cubosomes. The optimized PS loaded cubosomal formulation (CB6) characterized by studying the surface appearance (SEM & TEM analysis), particle size analysis, entrapment efficiency, in-vitro drug release, ex-vivo corneal permeation through goat cornea, anti-fungal activity against Candida albicans and stability. Results: The optimized cubosomes (CB6) had smooth surface and cubic shape, exhibit a particle size 183 nm, -17.15 mV zeta potential and 88.01% entrapment efficiency. When compared with marketed PS suspension (40mg/ml), the CB6 demonstrate sustained diffusion-controlled drug release, 2.8 fold higher increase in corneal permeability and improved anti-fungal activity against Candida albicans. Conclusion: Posaconazole-loaded cubosomes are a potential nanocarrier system for topical ocular administration of posaconazole and could be very useful in treatment approach for fungal keratitis.