Abstract:
Posaconazole is a broad-spectrum, second generation, triazole compound with antifungal
activity that is used to treat invasive infections by Candida species and Aspergillus
species in severely immunocompromised patients. But its poor solubility in water makes
it largely unavailable. Therefore HP-β-cyclodextrin is used to form inclusion complex
with posaconazole to improve its aqueous solubility without changing its antifungal
activity. The aim of the present study was to formulate and evaluate mucoadhesive
vaginal tablet containing posaconazole-HP-β-CD complex to achieve good therapeutic
effect with good mucoadhesion which ultimately reduce the dosing frequency in the
treatment of vaginal candidiasis and also enhances the bioavailability of drug.
Mucoadhesive vaginal tablet containing chitosan and HPMC K15M were used as
mucoadhesive polymers to increase the residence time of the formulation in vagina and
effervescent mixture (sodium bicarbonate: citric acid) was incorporated into the
formulations to enhance the swellability of formulation. Drug excipients compatibility
study was carried out using Fourier transform infrared spectroscopy which shows that
neither drug decomposition nor drug-excipients and excipients-excipients interactions
occurred in the formulation. Optimization of formulation was done using 32 full factorial
design for optimization of the concentration of chitosan and HPMC K15M. All the
formulation were evaluated for weight variation, hardness, thickness, drug content,
swelling index, ex-vivo mucoadhesion study and in-vitro drug release study of the tablets
in simulated vaginal fluid with different proportions of mucoadhesive polymer and effervescent in formulations. An optimized batch containing 100 mg polymer mixture of
chitosan: HPMC K15M in ratio of 1:2 and 30 mg of effervescent mixture showed good
controlled release effect and moderate bioadhesion in terms of weight variation, hardness,
thickness, drug content, % swelling index, ex-vivo mucoadhesion study and in-vitro drug
release study. The stability studies showed that the developed mucoadhesive vaginal
tablet formulation was stable after one month as there is no significant changes in %
swelling index, ex-vivo mucoadhesion study and drug content for period of one month.
Thus, our present study provides a potential therapeutically effective vaginal tablet
formulation of posaconazole for vaginal delivery.