Preparation, physicochemical characterization, and In vivo evaluation of miconazole nitrate nanosponges for the treatment of systemic mycoses

Abstract

Miconazole is a Biopharmaceutics Classification System (BCS) class II drug, thus limiting its oral bioavailability. Nanosponges can improve the oral bioavailability of poorly soluble drugs and sustain their release. The work was aimed at formulating miconazole nanosponges to enhance its solubility and consequently, oral bioavailability. Batches of nanosponges incorporating different concentrations (1, 2 and 3 %) of miconazole nitrate were formed using ethyl cellulose (EC), polyvinyl alcohol (PVA), ethanol and Kolliphor® 188. They were characterized using percentage yield, encapsulation efficiency, Differential Scanning Calorimetry (DSC), Xray Diffraction (XRD), particle sizes, polydispersity index (PDI) and Scanning Electron Microscopy (SEM). In vitro antifungal evaluation against Candida albicans was assessed while in vitro release using simulated gastric fluid was done. Furthermore, in vivo release studies in rats were carried out using the bioassay method. The percentage yield of the nanosponges were between 50 to 60 %. Encapsulation efficiencies ranged between 77 and 98 %. Particle sizes ranged between 266.5 and 781.1 nm. Particles were porous and spongy in appearance. Antifungal evaluation of the nanosponges against Candida albicans revealed activity like that of the pure drug. In vitro release studies showed a sustained release pattern for the nanosponges up till 12 hours whereas the unformulated drug peaked at 2 h. In vivo evaluation showed a concentration dependent increase in blood concentration of the drug with NS4 having the highest release. Nanosponges containing miconazole nitrate were successfully formulated and evaluated and are a promising oral delivery system for miconazole nitrate.