ABSTRACT:
Aim of this research was formulation matrix tablets of trimetazidine with extended release (ER), and evaluation the influence of different types and concentrations of polymers on release of drug in vitro. Six formulations F1 – F6 were manually designed by wet granulation using different proportions and amount of polymers. The formulations of ER matrix tablets (F1 – F6) were composed of using different polymers such as, hydroxypropyl methylcellulose (HPMC-?100?), hydroxypropyl cellulose high viscosity (HPCh), carboxymethyl cellulose (CMC), ethylcellulose (EC-10 cps), carbopol-940. All ER formulations contained polyvinylpyrrolidone (PVP-?30), microcrystalline cellulose (MCC), dibasic calcium phosphate and magnesium stearate. The PVP-?30 and magnesium stearate were used in a fixed quantity in all ER formulations. The effect of polymer viscosity, its proportion and co-formulation of polymeric excipients in prepared tablets on trimetazidine release from all formulations was studied. Data drug release in vitro was performed in phosphate buffer of pH 7.4 by analytical method, because cellulose polymers are insoluble in gastric fluid. The amount of released trimetazidine was calculated by preparing standard series in phosphate medium. Dissolution profile indicated that formulations F1 and F2 extended the drug release for 16h. Formulations F3 and F5 released 92.28%, 87.72% of their content during 12h respectively. While formulations F4 and F6 released 72.09%, 58.5% of their content within 16h consecutively, thus their effect can last for more than a day due to the high viscosity and amount of polymers. MS Excel was used to analyze the in vitro release kinetics profile data such as Zero-order, first order, Higuchi and Korsmeyer–Peppas models. However, formulations (F1, F2) containing polymers (HPMC -?100?, HPMC and EC) as a matrix former showed drug release as highest correlation coefficient (r2) values obtained when Korsmeyer-peppas model was applied (r2 = 0.9801 – 0.9713) respectively. Formulation F3 containing (HPMC and CMC) showed the highest correlation coefficient (r2) value when first order model was applied (r2 = 0.9885). While formulation (F5) containing hydrophobic polymer (EC-10cps) showed concentration-independent drug release as highest linearity was observed when zero-order model was applied (r2 = 0.8916). Whereas, formulations (F4, F6) containing (Carbopol-940, HPCh) as a matrix former showed the highest correlation coefficient (r2) values when higuchi-order model was applied (r2 = 0.9804, 0.9317) consecutively. Release mechanism of trimetazidine from all formulations was Case II relaxation mechanism (Erosion release). The present study showed that cellulosic derivatives polymers can be used successfully for developing and controlling directly release of matrix tablets formulation.