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The research aimed to formulate and prepare hydrogel of low molecular weight chitosan nanoparticles with the help of antifungal agents such as clotrimazole and Nystatin for the topical application. Using the ionic gelation process, placebo and nanoparticles containing drugs were prepared. By cationic interaction is suitable for pH, and gel sodium tripolyphosphate is used as a crosslinker which cross-links the chitosan particles to form the gel, interaction between drug and polymer was observed during the formulation development. Formulated nanoparticle with chitosan and nystatin and clotrimazole showed the mean diameter 273.7nm, 983nm, and 501nm. Clotrimazole and Nystatin had encapsulation capacity was about 74.6% and 63.0%, respectively. In vitro drug release at pH 4.7 chitosan molecules are examined for the version of clotrimazole and nystatin.it has noticed that both the formulation shows sustained drug release about 12 hours. Using SEM, nanoparticles are directed for surface morphology character; it shows that nanoparticles are smooth and spherical in structure. Chitosan itself has the antimicrobial property; it was carried out for the antifungal activity against the fungus Candida Albicans along with the prepared formulations drugs for the comparative study. And the result showed that clotrimazole had maximum fungal growth inhibition next followed by the nystatin and chitosan is least. This inhibitory effect was due to the parameter such as zeta potential and particle size of chitosan nanoparticles. And it shows the least antifungal activity of nanoparticles, which are formulated from the TMC. Hence CTZ and Chitosan were formulated and applied as a natural antifungal agent into nanoparticle to increase the fungal activity. According to the ICH Q1A (R2) guidelines, stability studies are conducted to prove no degradation of the drug. The prepared formulation of chitosan nanoparticles based hydrogel incorporated with clotrimazole and nystatin are promising and significant properties for the efficient treatment of topical fungal infections
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