Development and in vitro Evaluation of Voriconazole Nanoparticle Formulation for Mucosal Application

This study aimed to prepare and evaluate mucoadhesive nanoparticle formulations of voriconazole, an antifungal drug, for mucosal application. It was also aimed to develop and validate a HPLC method of voriconazole.

In this study, mucoadhesive nanoparticles containing voriconazole were prepared using a coating polymer of chitosan. The obtained nanoparticles were characterized via particle size, polydispersity index, zeta potential measurement, and mucoadhesion studies. Drug loading capacity was tested for determination of the voriconazole amount in the nanoparticles. In vitro drug release was also examined. The HPLC method was validated for linearity, accuracy, precision (repeatability and reproducibility), specificity, stability, limits of detection (LOD), and limit of quantification (LOQ).

In vitro characterization results of the mucoadhesive nanoparticle formulation containing voriconazole was found to be appropriate with a small particle size of 217.1±4.2 nm, a narrow polydispersity index of 0.335±0.042, 99.052±0.424% drug loading, and a positive zeta potential value of +26.82±0.4 mV. Accor-ding to a mucoadhesive study, it can be concluded that the nanoparticle was able to interact with mu-cin due to ionic interaction. Also, the turbidity of nanoparticle/mucin dispersion was higher than the turbidity of mucin dispersion itself. Based on the in vitro drug release, no burst effect was observed, indicating that voriconazole was homogeneously dispersed in the nanoparticle dispersion and that no significant amount of drug was adsorbed onto the nanoparticle surface. The release was found to fol-low a non Fickian diffusion mechanism with first order drug release. The proposed HPLC method was simple, highly sensitive with good linearity, accurate, precise, specific, and stable, showing that the method is useful for routine quality control.

This study has shown that the mucoadhesive nanoparticle formulation containing voriconazole repor-ted here is a promising candidate for the local treatment of mucosal diseases. The developed HPLC method can be succesfully applied to pharmaceutical preparations containing voriconazole.