Design, Optimization and Characterization of Clotrimazole Loaded Eudragit EIOO Polymeric Nanoparticles

Abstract

Oral candidiasis is one of the most common fungal infections that occur worldwide most commonly in the infants and the itmnunocompromised individuals. It is caused by candida species most conunonly candida albicans. Recently, Candida infections have increased significantly due to the emergence of the fatal infections (Rex et aI., 2000). It is characterized by the development of white patches in the oral cavity and on the surface of tongue. Different drugs are beit1g used to treat the infection such as the itnidazoles antifungals but major problem is that the oral admll1istration of the drugs leads to severe side effects and the topically admit1istered drugs have very short residence time in the buccal cavity and hence frequent dosing is required. Clotritnazole is a broad spectrum imidazole antifungal that is used to treat the infections caused by candida. It interferes with the synthesis of ergosterol which is essential component of the fungal membranes. It has fungistatic activity. The problem associated with its oral administration is that it has very poor aqueous solubility and causes severe GI side effects. The torches available for the treatment have to be administered 5 titnes daily which reduces the patient compliance. The aim of the study was to develop a mucoadhesive gel containing CTZ loaded EE 100 nanoparticles. The rationale was to increase the local bioavailability of the drug and enhance the buccal residence titne leading to greater efficacy. The polymeric nanoparticles were prepared by the solvent displacement method and then optitnized by applying the design expert software. The polymeric nanoparticles were prepared using the EEIOO polymer and the pluronic F-127 as surfactant. The formulation was optitnized by varying the drug, polymer and surfactant concentrations. The response variables were particle size, entrapment efficiency and zeta potential. The optitnized formulation was physicochemically characterized in terms of particle size, PDI and zeta potential. XRD and FTIR analysis were canied out. Entrapment efficiency study was also performed. FTIR studies were conducted to check any chemical interations between the drug and the excepients. XRD studies were performed using X-ray diffractometer. Ex vivo permeation studies, mucosal retention studies andin vitro drug release studies were performed to check the release of the drug at specific pH. The optimized formulation was observed to have the particle size of 256.3 lUn, PDI of 0.24 and zeta potential of +23.2 mY. The v entrapment efficiency of the fonnulation was 88% calculated by the indirect method. The FTIR spectra of the fonnulation, drug and polymer were compared and no incompatibility was observed. No chemical interaction was found. XRD analysis showed no characteristic peaks in the formulation which showed that the crystalline form of the drug was changed to the amorphous nature and drug was encapsulated within the polymeric nanoparticles. The nanoparticles were loaded in the mucoadhesive gel to increase the viscosity and buccal residence time. Ex vivo penneation studies were performed using the Franz diffusion cell to detennine the permeability of the drug in the mucosal layers. Permeation was enhanced in the NP gel as compared to the plain gel. The release data was compared between the CTZ loaded NP and the drug suspension and the NP gel and the plain gel. The in vitro release data showed the sustained drug release from the CTZ nanoparticles as compared to the suspension and maximum drug was released in a more sustained manner from the CTZ NP gel over the time when compared with the plain gel hence sustained drug delivery was achieved. The prepared c1otrimazole polymeric nanopartic1es gel had promising potential to enhance the buccal residence time of the drug and hence better therapeutic efficacy. Increased contact time and sustained drug delivery will also unprove the patient compliance.