Study On The Osmotic Pump Controlled Release Tablets Of Nimodipine

Nimodipine is a dihydropyridine calcium channel blocker, used in the treatment ofhypertension, ischemic damage in clinical, subarachnoid hemorrhage and so on. The drugis practically insoluble in water，poor absolute bioavailability.The biological half-life ofnimodipine is about1.5~2h and the bioavailability is only5%~13%in healthy people, sothe administration is frequent. A new drug delivery system needs to be designed in orderto improve bioavailability, reduce administration. Osmotic pump controlled releasetablets (OPCT) delivery drugs at a constant speed, which slow down the phenomenon ofthe peak valley of blood drug concconcentration. At the same time, the drug release fromthe osmotic pump tablets was independent of the medium, food, peristalsis and pH of GI.The lag time, extremely cumulative release and integrity of membrane wereselected as indicators to optimize the formulations, included solubilizers, suspendingagents and pore-formers. The optimal formulation delivery drugs according tozero-model release during12h and the extremely cumulative release of nimodipine wasmore than90%.An UV method for drug delivery and an HPLC method for the determination ofcontent and related substances of Nmodipine osmotic tablets were established, and theresults demonstrated that the methods were simple, accurate, sensitive and applicable forthe quality control of Nimodipine osmotic tablets.The results of influencing factor indicated that nimodiping osmotic pump controlledrelease tablets were stable except RH92.5%.HPLC-MS/MS mhetod was developed to quantify the durg plasma concentration ofbeagle dogs, and the study of pharmacokinetics was carried out in a single dose,randomized, two-period crossover experimental design. Nimodipine sustained releasetablets Yunmen erping (SRT) were selected as reference. The maximum plasmaconcentrations (Cmax), times to reach maximum concentrations (Tmax), mean residence time (MRT), and the area under the plasma concentration–time curves (AUC) from0to24h were76.62±8.56ng/mL,2.29±1.52h,3.83±0.70h,325.45±23.27ng h/mL forOPCT and137.69±18.47ng/mL,2.17±0.82h,2.98±0.51h,444.28±17.32ng h/mLfor SRT. The relative bioavailability of NMP OPCT was98.54%compared to SRT,which showed the two treatments were bioequivalent. The correlation betweenabsorption in vivo and percentage of NMP dissolved in0.5%SDS wasy=0.9745x+37.483(R~2=0.9168) for OCPT, and y=0.0.5219x+65.85(R2=0.6486) for SRT,which demonstrated that OCPT had a better correlation between absorption in vivo and invitro.