Design, optimization and in vitro - in vivo evaluation of bilayer floating tablets of diltiazemHCl by using xanthan gum and guar gum in healthy human volunteers

The objective of the present research work was to develop the bilayer floating tablets of Diltiazem HCl using superdisintigrants for the immediate release layer as loading dose for immediate action and HPMC K-4M, K-15M and K-100M polymers for the sustained release layer to deliver the drug at sustained or controlled manner in GIT and consequently in to systemic circulation by direct compression method. Bilayer floating tablets were punched using optimized immediate release layer and floating layer as sustained release layer. Tablets were evaluated for compatibility study, buoyancy lag time, total floating time, swelling study, in-vitro disintegration and in-vitro dissolution studies. Formulations were found uniform with respect to thickness (5.00 to 5.08 mm) and hardness (4.7 to 5.2 kg/cm2). The friability (0.32 to 0.44%), weight variation (498 to 502 mg) and Drug content (96.34 to 99.49%) of different batch of tablets were found within prescribed limits. Formulation F7 selected as best formulation, shown buoyancy lag time of 41 sec, total floating time of more than 12 hrs and drug release of 98.12% in a period of 12 hrs. Optimized formulation (F7) followed diffusion controlled first order kinetics and fickian transport of the drug. FTIR and DSC studies revealed the absence of any chemical interaction between drug and polymers used. Approximately 37% of drug was released from optimized formulation within 1 hr and total of 98.12% of drug was released without dose dumping for extended period of 12 hr. The optimized formulation (F7) showed no significant change in physical appearance, drug content, floatability or in vitro dissolution pattern after storage at 400C/75% RH for three months. It was determined by the radiographs that floating tablets prepared by adding barium sulphate stayed in the stomach for 6.5 h. The comparison of in vivo bioavailability studies of optimized formulation F7 of bilayer floating tablet and reference formulation (DILZEM SR) in human healthy volunteers confirmed that the increase in diltiazem hydrochloride systemic exposure early after administration for immediate action and remaining drug was released in sustained manner from bilayer floating tablet by increasing the gastric residence time.