design and in vitro evaluation of a novel controlled onset extended-release delivery system of metoprolol tartrate

blood pressure rises rapidly upon awakening and maybe responsible, in part, for the increased incidence of myocardial infarction and stroke during the morning hours. the aim of the present study was, therefore, to develop a novel chronotherapeutic formulation of metoprolol tartrate (mt) for night time dosing providing maximum effect in the morning hours. core tablets contained mt, sodium chloride, lactos, avicel ® and starch. powders were mixed, sieved and directly compressed in to tablets using a single punch tablet machine. core tablets were then coated with 5 or 10% hydroxypropylmethylcellulose as swelling layer and subsequently outer membrane with the mixture of various ratios of eudragit ® rs to rl at different coating levels 5, 10, 15% as semi-permeable water insoluble outer coat by conventional pan-spray method. the best formulation with regard to release behavior was chosen and subjected to further release studies in various rotational speed and phs. both lag time and release rate were dependent on the coating levels and the osmotic pressure of dissolution medium. a linear relationship between lag time and outer coating levels was observed. the lag time was prolonged with an increase in the coating levels. both diffusion and osmotic pumping effect were involved in drug release from the device. significant increases in drug release behavior was not observed using dissolution medium with various ph and different agitation rates. it was found that the release rate was independent of ph, rotational speed and gastric motility and may not be altered due to changes of ph and peristaltic movement along the gi tract.