Preparation of candesartan cilexetil core-in-cup tablets with pulsatile release properties and its effect on the blood pressure of rabbits

Pulsatile drug delivery system，capable of releasing drug at the predetermined times according to clinical therapeutic requirements，can be used to treat several rhythmic diseases.Majority of individuals experience the rise in the blood pressure in the early morning hours，which potentially leads to serious cardiovascular complications.The purpose of the study was to develop pulsatile candesartan cilexetil core-in-cup tablets according to human circadian rhythm of blood pressure.The factors influencing t_lag were evaluated by in vitrodrug release and tablet erosion observations.In addition,the jugular artery pressuresvstimes courses of rabbits were recorded after oral administration of commercial candesartan cilexetil tablets or the developed core-in-cup tablets.The quantity and characteristics of the excipients in top layers in the tablets were found to modify t_lag.In vivo studies showed that the onset times indicating the decreases in the blood pressures of commercial tablets and core-in-cup tablets were (98±17) min and (278±29) min，respevtively.In vivo t_lag of the prepared core-in-cup tablets was (180±34) min in rabbits，which is consistent with the goal of design.