Co-processing of fluconazole with menthol for enhanced dissolution and anti-fungal activity: Preparation of orodispersable tablets

The objective was to enhance the dissolution rate and anti-fungal activity of fluconazole. Mixtures of fluconazole with menthol were subjected to ethanol aided kneading. The developed solids were characterized using Fourier transform infrared spectroscopy, differential scanning calorimetry and X-ray diffraction in addition to monitoring fluconazole dissolution. These investigations reflected formation of eutectic mixture. Eutexia was associated with enhancement in fluconazole dissolution. Formulation containing fluconazole with menthol at 1:1 M ratio was prepared as oral dispersible tablet which exhibited flash disintegration with subsequent fast dissolution of fluconazole. Mice oral candida model was used to assess the prophylactic and therapeutic effects of the developed menthol-containing tablet. Candida infection was achieved by swabbing the tongue and oral cavity of immunocompromised mouse using small cotton buds impregnated with candida suspension. Prophylactic protocol started 2.5 h post infection and treatment protocol started 3 days post infection. Macroscopic observation of infected untreated mice revealed white patches covering parts of the tongue with CFU values in the range of 110-4.6 x 106 CFU/ml. Disease progression in case of menthol containing tablet was much smaller compared to fluconazole tablet. The study introduced menthol containing tablet for fast liberation and improved anti-candida activity of fluconazole.

Automated summary

The objective of this study was to improve the dissolution rate and anti-fungal activity of fluconazole by preparing solid mixtures with menthol. The developed solids were characterized using various techniques and the dissolution of fluconazole was monitored. A menthol-containing oral dispersible tablet was prepared and its prophylactic and therapeutic effects were evaluated using a mouse oral candida model. The results showed that the menthol-containing tablet exhibited improved anti-candida activity compared to fluconazole tablet.