DEVELOPMENT AND EVALUATION OF CLOZAPINE PELLETS FOR CONTROLLED RELEASE

This research work was done to design oral controlled release matrix pellets of water insoluble drug Clozapine, using blend of Hydroxypropyl cellulose and glyceryl palmito stearate as as matrix polymers, methyl crystalline cellulose as spheronizer enhancer,sodium lauryl sulphate as pore forming agent. Clozapine formulations developed by the pellitization technique by drug loaded pellets were characterized with regard to the drug content, size distribution, Scanning electron microscopy, differential scanning calorimetry, fourier transform infrared spectroscopy and Xray Diffraction study. Stability studies were carried out on the optimized formulation for aperiod of 90 days, 40 ± 2 oC and 75 ± 5% relative humidity. The drug content was in the range of 95.34 – 98.12 %. The mean particle size of drug loaded pellets was in the range 1018 to 1065 mm. SEM photographs and calculated sphericity factor confirms that the prepared formulations were spherical in nature. The drug loaded pellets were stable and compatible as confirmed by DSC and FTIR studies. XRD patterns revealed the crystalline nature of pure clozapine. Loose surface crystal study indicated that crystalline clozapine was observed in all formulation and more clear in formulation A5. Higher amount of clozapine released was observed from formulation A5 and Syclop 25 mg tablet as compared to all other formulations and mechanism of drug release followed Fickian diffusion. It can be concluded that formulation A5 is an ideal formulation for once a day administration.