In vivo Assessment of Diltiazem HCl Immobilized Co-polymeric pH Sensitive Microgels

Abstract

Novel stimuli responsive coplymeric (2-ethyl hexyl acrylate -co- itaconic acid diltiazem HCl loaded microgels were fabricated and characterized successfully to reduce the degradation of drugs in acidic pH of stomach resulting in reduced bioavailability to minimize dosing frequency and enhance patient compliance. To evaluate the clinical significance, in-vivo studies of recently prepared novel pH sensitive copolymeric microgels are performed and different pharmacokinetic parameters as maximum plasma concentration (Cmax), time to reach the maximum plasma concentration (Tmax), area under the plasma concentration-time curve (AUC 0-?), half-life (t 1/2?) and elimination rate constant (K21) are analyzed. The mean plasma concentration of sustained release DLZ loaded microgels showed higher Tmax for prepared microgels (4.0758±0.22 hrs) than standard drug solution. The half-life t1/2? of test microgels is relatively higher (5.68±5.86 hrs) whereas the Cmax is measured to be 41.06±2.02ng/ml for microgels with AUC0-? calculated as 460.35±39.99 ng.hr/ml. Elimination rate constant K21 for DLZ microgels is 0.18 ± 0.07 hrs-1 for which showed the absorption phase is extended and drug is present for a prolong period of time in the body. This study proved that novel prepared pH sensitive copolymeric p(EHA-co-IA) microgels released model drug in sustained release manner in pH sensitive medium.