Development and Optimization of Intravaginal Mucoadhesive Microspheres of Econazole Nitrate

Abstract

The most common disease in the female vaginal tract is vaginal candidiasis caused by the microbe
Candida Albicans. The conventional formulation for the treatment of this disease shows a lack of retention of
the dosage form in the vaginal cavity due to the natural draining of vaginal fluid that leads to leakiness and
Messiness, which tends to escape during normal routine work. The mucoadhesive delivery of antifungal drugs in
the treatment of vaginal candidiasis is an alternative to delivering drugs for a longer time. In this research work,
econazole nitrate-loaded mucoadhesive microspheres were developed by spray drying method and compressed
into a vaginal tablet which disintegrates rapidly into microspheres in the vaginal cavity and adheres to vaginal
mucosa for a longer time. Methods and Materials: Econazole nitrate-loaded microspheres were prepared and
characterized in terms of particle size, drug loading, ex vivo mucoadhesion study, and in vitro drug release study.
A three-factor and three-level Box–Behnken design was employed to optimize the formulation, and the effect
of independent variables HPMC K 100M, Eudragit RSPO, and Eudragit RLPO on formulation was analyzed.
Results and Discussion: The particle size of the optimized formulation was found to be 25μ. The drug loading
and in vitro release study at 6 h were 23% and 93%, respectively. The data from the in vitro drug release study
show that the drug is released in a sustained manner due to release retarding polymer Eudragit RSPO and Eudragit
RLPO and the % mucoadhesion of the optimized microsphere was found to be 70 % after 8 h in contact with vaginal
fluid due to mucoadhesive property of HPMC K100M, tablet disintegrate rapidly into microsphere which adheres
to the vaginal wall and consistently release drug up to 6 h. Conclusion: The mucoadhesive microsphere prepared
by the spray dryer provides a mucoadhesion phenomenon that allows the adherence of the microsphere to the
vaginal mucosa so that drug retention time is increased. The prepared vaginal tablet overcomes the drawback of
conventional formulations and disintegrates rapidly into a mucoadhesive microsphere and adheres to the vaginal
lumen so that the retention time of the drug is increased.