Development and Clinical Evaluation of Mucoadhesive Gastroretentive Tablets of Dipyridamole

Abstract

The present research work was focused to develop a mucoadhesive tablet dosage form for dipyridamole, which shows pH dependent solubility, it is highly soluble in acidic pH and as the pH increases the solubility of the drug decreases. Hence it was selected as the drug candidate for the present research. Mucoadhesive tablets of Dipyridamole were successfully prepared by using polymers like HPMC K4M, Chitosan and Isabgul husk by wet granulation method. FT-IR studies showed that there is no incompatibility between drug, polymer and various excipients used in the formulations. Formulated tablets have shown satisfactory results for physical parameters and complied with the pharmacopeial limits. The ex-vivo mucoadhesive strength and mucoadhesive force was found to be in the range of 16.15- 21.20 g and 1.56-2.06 N. Total ex-vivo mucoadhesive time was observed in between 10 to 12 hours. The in-vitro drug release was found to be more than 90% for the formulations FMD2, FMD3 and FMD8, up to 12 hours. Based on in-vitro drug release and mucoadhesive properties, formulation FMD2 was selected as optimized formulation. The dissolution data were further characterized by fitting the data into various kinetic models. The drug release from the matrices followed zero order with non-fickian release (diffusion + erosion controlled) for the optimized formulation. The optimized formulation was further subjected to swelling studies, which showed a swelling index of 286% up to 24 hours. The results indicated that the selected polymers were of swellable type. The stability studies were carried for 6 months as per ICH and WHO guidelines and the results of the stability study revealed that the optimized formulation is stable during the storage period. The in-vivo radiographic studies in fed condition, for the Mucoadhesive tablets (FMD2) showed a gastric residence time of more than 6 hours. When the radiographic images were taken at different time intervals and it was found to be in a particular location, which suggested that the retention of the dosage form might be due to the adhesion of dosage form to the gastric mucosa.