Vaginal
candidiasis is a common form of
infection in women caused by Candida species. Due to several drawbacks of conventional treatments, the current research is attempted to formulate and optimize a
miconazole nitrate-loaded in situ spray gel for vaginal
candidiasis. The stimuli-responsive (pH and thermo-responsive)
polymers selected for the in situ gel were
chitosan and
poloxamer 407, respectively, whereas
hydroxypropyl methylcellulose (HPMC) was introduced in the formulation to further improve the mucoadhesive property. The dispersion of each
polymer was carried out using the cold method, whereas the optimization of the formulation was achieved using Box-Behnken statistical design considering viscosity and gelation temperature as dependent variables. Present design achieved the optimized outcome with HPMC,
poloxamer and
chitosan at 0.52% (w/v), 18.68% (w/v) and 0.41% (w/v), respectively. Evaluation of
drug-
excipients compatibility was performed using differential scanning calorimetry, Fourier transform infrared spectroscopy, and thermogravimetric analysis where the results showed the absence of any chemical interaction between the
polymers and
drug component. The optimized formulation showed gelation temperature at 31°C allowing in situ phase transition in a vaginal environment; pH of 4.21 is suitable for use in the vaginal cavity, and appropriate viscosity (290 cP) at storage temperature (below 30°C) would allow spraying at ease, whereas strong mucoadhesive force (22.4±0.513 g) would prevent leaking of the formulation after application. The drug release profile showed sustained release up to 24 h with a cumulative drug release of 81.72%, which is significantly better than the marketed
miconazole nitrate cream. In addition, an improved antifungal activity could be correlated to the sustained release of the
drug from the formulation. Finally, the safety of the formulation was established while tested on HaCaT cell lines. Based on our findings, it could be concluded that the
in situ hydrogel formulation using
stimuli-responsive polymers could be a viable alternative to the conventional
dosage form that can help to reduce the frequency of administration with ease of application to the site of
infection, thus will provide better patient compliance.