Pharmacokinetic Studies of Gastroretentive Mucoadhesive Matrices for Diltiazem Hydrochloride Using Some Natural Polysaccharides

Abstract

The objective of this study was to investigate differences in the pharmacokinetic patterns between a gastroretentive mucoadhesive drug delivery system (GRMDDS) and sustained release dosage form of same dose to increase the residence time of the drug in to the stomach and release for extended period of time. Gastroretentive mucoadhesive tablets of diltiazem hydrochloride (DLTH) with hibiscus esculentus mucilage and xanthan gum as natural polysaccharides were developed for mucoadhesive sustained drug release by wet granulation technique. In-vivo gastro retentive mucoadhesion study confirmed stomach retention for more than 10 h. In-vivo pharmacokinetic studies in rabbits showed Cmax of 176.86 ng/ml and Tmax of 13.3 h for GRMDDS. AUC0–t and AUC0–8 for mucoadhesive tablet formulation was 2514.61 and 3145.77 while the marketed formulation was 2220.11 and 2750.36 ng.h/ml respectively. The point estimates (90% CI) of the “test/reference” mean ratio for Cmax, AUC0-t and Tmax were 1.0662, 1.0327 and 1.33. The difference for AUC0–t and AUC0–8 between the test and reference formulation was statistically significant (p<0.05). Non superimposition of the percent in-vivo absorption and in-vitro dissolution curves was observed to investigate a multiple point correlation of in-vivo and in-vitro which might suggest the possibility of the existence of a level A correlation using the optimum dissolution condition. The results of the present study indicate that the oral bioavailability of diltiazem hydrochloride is significant increase when its dosage is provided prolonged gastric residence by GRMDDS.