Formulation and Optimization of Immediate Release Pellets of Antiplatelet Drugs Using Design of Experimentation

Abstract

Platelets play an important role in hemostasis during tissue injury, which blocks the defect and terminates blood loss. Platelet aggregation inhibitors are widely used in treatment of cardiovascular disorders and Peripheral arterial disease. Clopidogrel bisulphate and Cilostazol, are FDA approved BCS class II drugs, used in treatment of Platelet aggregation, peripheral arterial disease and intermittent claudication. The aim of the present study was to develop an immediate release pellets for combination of Clopidogrel bisulphate and Cilostazol using extrusion spheronization technique. The effects of spheronization speed(X1) and binder concentration (PVP K30) (X2), on size of pellets, disintegration time and drug release were studied using 32 full factorial design. The surface response and counter plot were drawn to facilitate an understanding of the contribution of the variables and their interaction. From the results, speed of spheronization of 1100 rpm and 5% concentration of PVP K30, were selected. In vitro drug release studies revealed more than 80% of clopidogrel bisulphate release and more than 75% of cilostazol release within 30 min of dissolution which complied with the pharmacopoeal limits. Film coated pellets did not show significant change in the drug release. DSC and FTIR studies revealed no interaction of drugs and excipient during pellet formulation. The pellet formulations of clopidogrel and cilostazol were found to be stable when stored at 40ºC±2ºC/ 75%RH±5%RH for 2 months. Conclusively, clopidogrel bisulphate and cilostazol pellet fixed dose combination could be successfully developed by design of experimentation and complied with pharmacopoeal limits.