DEVELOPMENT OF GASTRORETENTIVE FLOATING TABLETS OF DILTIAZEM HYDROCHLORIDE AND ITS STATISTICAL OPTIMIZATION

This study aimed to develop gastroretentive floating tablets of diltiazem hydrochloride, using a release retarding polymer and to apply statistical approach of response surface methodology for further formulation optimization. Response surface methodology using the central composite design was used to study the effect of formulation variables on the floating lag time (FLT), time taken for 90% of drug to be released (t(90%)) and total floating time (TFT), and to optimize the formulations. The floating tablets were prepared using direct compression method using Polyethylene Oxide (PEO WSR) coagulant as the release retarding polymer and sodium bicarbonate as the gas generating agent. A 3(2) factorial design was applied to optimize the drug release profile. The quantity of PEO WSR coagulant and concentration of sodium bicarbonate were selected as the independent variables. The floating lag time (FLT) and total floating time (TFT) of conventional formulations (BC1 - BC4) were varied from 10 - 40 sec and 6-8 hrs respectively. The FLT of statistical formulations (BS1 - BS9) were in the range of 5 - 53 sec and the TFT for the same formulations were in the range of 0.12 - 10 hrs. The statistically optimized formula suggested by the central composite design was 34.45 mg of PEO WSR coagulant and 30 mg of sodium bicarbonate. The statistically optimized formulation passed all the physicochemical tests. From the in vitro buoyancy studies, the FLT of the statistical optimized formulation (Bso) was found to be at 19 sec. The experimental t(90%) and TFT were 6.4 hours and 8.5 hours respectively. The calculated relative errors of all variables were within 5%, concluding that the statistically optimized formulation is valid. The applied FTIR and DSC studies on the statistically optimized formulation led to the conclusion that there were no interactions between drug and polymer.