Formulation and in vitro evaluation of once-daily methyldopa sustained release matrix tablets

Methyldopa, an anti-hypertensive drug having a half life of less than 2 hours, and given with a dose of 250 mg 3-4 times daily. Objective: The present study was for objective of developing a sustained release (SR) matrix tablets of methyldopa using hydroxypropyl methylcellulose(HPMC) as release controlling factor, and to study the effect of some formulation factors on drug release from tablets. Methods: Hydrophilic SR matrix tablets containing 250 mg of methyldopa were prepared using wet granulation method. Granules were evaluated for moisture content, loose bulk density, tapped bulk density, compressibility index and hausner’s ratio. Tablets were subjected to physiochemical studies and in vitro dissolution study. Effect of concentration and viscosity grade of HPMC, both binder and lubricant concentration on drug release from matrix tablets was evaluated . Results: All formulations showed physiochemical properties which appear to be in compliance with pharmacopeial standards. From the in vitro dissolution studies, it was clear that as the concentration or viscosity of polymer increased, the rate of drug release was found to be decreased. Higher concentration of binder (PVP K30) showed slower release of drug, while the level of lubricant(magnesium stearate and talc) appeared to insignificantly affect release rates. Drug release kinetics of about all formulations correspond best to Korsemeyer-Peppas model and drug release mechanism was found to be anomalous (non-Fickian) diffusion based on release exponent value. The formulation F6 (containing 15% HPMC K100M ) was selected as the optimized formulation as it sustained the release over 24 hrs. Conclusion: The results of this study showed that the drug release from HPMC based matrix tablets using methyldopa as a drug model could be modulated by varying the polymer concentration, the polymer viscosity and the binder concentration with no significant effect of varying the lubricant concentration.

Methyldopa, an anti-hypertensive drug having a half life of less than 2 hours, and given with a dose of 250 mg 3-4 times daily. Objective: The present study was for objective of developing a sustained release (SR) matrix tablets of methyldopa using hydroxypropyl methylcellulose(HPMC) as release controlling factor, and to study the effect of some formulation factors on drug release from tablets. Methods: Hydrophilic SR matrix tablets containing 250 mg of methyldopa were prepared using wet granulation method. Granules were evaluated for moisture content, loose bulk density, tapped bulk density, compressibility index and hausner’s ratio. Tablets were subjected to physiochemical studies and in vitro dissolution study. Effect of concentration and viscosity grade of HPMC, both binder and lubricant concentration on drug release from matrix tablets was evaluated . Results: All formulations showed physiochemical properties which appear to be in compliance with pharmacopeial standards. From the in vitro dissolution studies, it was clear that as the concentration or viscosity of polymer increased, the rate of drug release was found to be decreased. Higher concentration of binder (PVP K30) showed slower release of drug, while the level of lubricant(magnesium stearate and talc) appeared to insignificantly affect release rates. Drug release kinetics of about all formulations correspond best to Korsemeyer-Peppas model and drug release mechanism was found to be anomalous (non-Fickian) diffusion based on release exponent value. The formulation F6 (containing 15% HPMC K100M ) was selected as the optimized formulation as it sustained the release over 24 hrs. Conclusion: The results of this study showed that the drug release from HPMC based matrix tablets using methyldopa as a drug model could be modulated by varying the polymer concentration, the polymer viscosity and the binder concentration with no significant effect of varying the lubricant concentration.