In Vivo Testing and Extended Drug Release of Chitosan-Coated Itraconazole Loaded Microemulsion Using Volatile Oil Thymus vulgaris

Abstract

Microemulsions are potent drug delivery vehicles as they solubilize water insoluble drugs with poor bioavailability. The main aim of this study was to develop, optimize, and assess a thyme oil microemulsion with inherent antifungal activity for transdermal drug delivery of itraconazole. The optimized thyme oil microemulsion contains thyme oil, Cremophor EL, and water at 5:25:70% v/v respectively. The drug loaded microemulsion was mixed in equal proportion with chitosan for cutaneous application. The droplet size, zeta potential, FTIR spectra, and antifungal activity of the drug free microemulsion and drug loaded microemulsions with/without chitosan were characterized. The ex vivo drug permeation of drug loaded microemulsions with/without chitosan was compared with that of the bulk drug, using the Franz diffusion apparatus with the excised skin from Wistar rats. The droplet size of the drug free microemulsion and drug loaded microemulsions with/without chitosan were 25.53 ± 3.84 nm, 168.6 ± 13.33 nm, and 35.13 ± 0.41 nm respectively, with a polydispersity index between 0.436 and 0.658. The FTIR spectra demonstrated no changes in the structure of the drug in the drug loaded microemulsions with/without chitosan. The in vitro antifungal studies against Candida albicans exhibited similar zones of inhibition between bulk drug and drug loaded microemulsion, while the minimum inhibitory concentration showed a 2-fold decrease with drug loaded microemulsions with/without chitosan compared with the bulk drug. SEM confirmed substantial morphological changes in C. albicans cell membrane. The drug loaded microemulsion with chitosan revealed a slow and sustained release of itraconazole in phosphate buffered saline (pH 7.4) proving it to be an efficient, stable, and sustained topical delivery vehicle.