Novel drug delivery system of luliconazole - Formulation and characterisation

Abstract

Dermatophytes, a group of fungal species causing superficial fungal infections possess a major health problem in a wide group of people. Various approaches have been used in past for treatment of such infections but, owning to their low dermal permeability and less retention time, such formulations are proven to be less effective. Thus, to overcome such limitations, various novel drug delivery systems were developed. “Nanosponge” - a porous nano carrier system which can entrap drug of choice and improve its dermal availability, permeation rate and retention time is one such example. In the present study, a novel azole antifungal drug luliconazole, having wide spectrum of activity and potent against dermatophytes was used as model drug. It has low aqueous solubility and less dermal availability. A regular 2-level factorial design was applied using Design Expert® 11 software to formulate luliconazole loaded nanosponge drug delivery system using emulsion solvent diffusion method. Polyvinyl alcohol and ethyl cellulose were used as polymers. Formulated nanosponges were characterised for percentage entrapment efficiency, particle size, poly dispersibility index, zeta potential, surface morphology studies using scanning electron microscopy (SEM), transmission electron microscopy (TEM) and porosity. Fourier transform infrared spectroscopy, X-ray diffraction and differential scanning calorimetric analysis were also carried out to confirm the encapsulation of the drug within the carrier. In vitro release studies and other relevant parameters were also determined. Further, prepared nanosponges were incorporated into gel base using carbomer 934 and characterised for viscosity, swelling behaviour, spreadability, in vitro diffusion studies, skin irritancy test, in vitro permeation studies using rat skin membrane, antifungal activity and stability studies. From the results obtained it was evident that, formulated nano carriers were in desired nano size range having characteristic porous structure which was further confirmed by SEM and TEM studies. It was perceived that percentage drug entrapment efficiency was in the range of 70–80%. Drug release kinetics data revealed prolonged release up to 8 h. Release pattern was found to be diffusion controlled which was confirmed by Higuchi's plot. In vitro permeation studies revealed enhanced permeation rate and skin retention time. Collectively, the developed drug delivery system had greater permeation rate and increased retention time. Further, the formulation was found to be non-irritant and stable. Overall, the aim of enhancing dermal availability and sustaining the release of drug for effective fungal therapy was achieved by formulating as nanosponge gel.