Posaconazole loaded bilosomes as a novel vesicular carrier for topical treatment of fungal infections: Formulation, optimization, ex-vivo permeation and antifungal assay

Posaconazole (PSZ) is potent drug used in infections caused by Candida, Aspergillus species and many other fungal species. However PSZ belongs to BCS class II limiting its in vivo performance. The objective of current work was to mitigate the difficulties in topical delivery of PSZ overcoming its shortcomings such as aqueous solubility. PSZ loaded bilosomes were prepared and optimized using Box-Behnken design. The optimized bilosomes were characterized by TEM, DSC, FTIR, in vitro PSZ release, ex-vivo skin permeation and antifungal activity against Candida albicans and Aspergillus niger . The optimized spherical, unilamellar batch (PSZ_BIL) of bilosomes had vesicle size of 264.40 ± 5.17 nm and encapsulation efficiency of 97.54 ± 3.5 %. DSC studies revealed solubilization of PSZ in the molten mixture of cholesterol, poloxamer and sodium deoxycholate. FTIR spectra of PSZ_BIL suggested hydrogen bonding between PSZ and poloxamer in bilosomes responsible for greater entrapment efficiency. Further PSZ_BIL showed 2 fold increase in PSZ release when formulated into bilosomes. Ex vivo skin permeation studies showed 2.5 fold higher PSZ retention in rat skin when compared to PSZ gel. Additionally, local accumulation efficiency of PSZ was found to be 2.01 for PSZ_BIL gel formulation. The PSZ_BIL showed 2.33-fold and 1.8 fold increase in zone of inhibition for Candida albicans and Aspergillus niger respectively when compared to PSZ gel. Thus the prepared posaconazole loaded bilosomal gel could be an alternative to the existing formulation demonstrating the antifungal activity at much lower dose of the drug alone.