Zhao Shiqing, Yu Fanglin, Liu Nan, Di Zhong, Yan Kun, Liu Yan, Li Ying, Zhang Hui, Yang Yang, Yang Zhenbo, Li Zhiping, Mei Xingguo
a Beijing Institute of Pharmacology and Toxicology , Beijing , People's Republic of China.
Drug Dev Ind Pharm. 2016 Nov;42(11):1723-31. doi: 10.3109/03639045.2016.1171332. Epub 2016 Apr 13.
The synchronous sustained-release of two drugs was desired urgently for patients needing combination therapy in long term. However, sophisticated technologies were used generally to realize the simultaneous delivery of two drugs especially those with different physico-chemical properties. The purpose of this study was to obtain the concurrent release of felodipine and metoprolol tartrate, two drugs with completely different solubilities, in a simple monolithic osmotic pump system (FMOP). Two types of blocking agents were used in monolithic osmotic pump tablets and the synchronous sustained-release of FMOP was acquired in vitro. The tablets were also administered to beagle dogs and the plasma levels of FMOP were determined by HPLC-MS/MS. The pharmacokinetic parameters were calculated using a non-compartmental model. Cmax of both felodipine and metoprolol from the osmotic pump tablets were lower, tmax and mean residence time of both felodipine and metoprolol from the osmotic pump tablets were longer significantly than those from immediate release tablets. These results verified prolonged release of felodipine and metoprolol tartrate from osmotic pump formulations. The similar absorption rate between felodipine and metoprolol in beagles was also obtained by this osmotic pump formulation. Therefore, it could be supposed that the accordant release of two drugs with completely different solubilities may be realized just by using monolithic osmotic pump technology.
对于长期需要联合治疗的患者而言，迫切需要两种药物的同步持续释放。然而，通常采用复杂的技术来实现两种药物尤其是具有不同理化性质的药物的同时释放。本研究的目的是在简单的单室渗透泵系统（FMOP）中实现溶解度完全不同的两种药物非洛地平和酒石酸美托洛尔的同步释放。在单室渗透泵片中使用了两种类型的阻滞剂，并在体外实现了FMOP的同步持续释放。将该片剂也给予比格犬，并通过HPLC-MS/MS测定FMOP的血浆水平。使用非房室模型计算药代动力学参数。渗透泵片中非洛地平和酒石酸美托洛尔的Cmax均较低，渗透泵片中非洛地平和酒石酸美托洛尔的tmax和平均驻留时间均显著长于速释片。这些结果证实了非洛地平和酒石酸美托洛尔从渗透泵制剂中的缓释作用。通过这种渗透泵制剂还获得了比格犬中非洛地平和酒石酸美托洛尔之间相似的吸收速率。因此，可以推测仅通过使用单室渗透泵技术就可以实现两种溶解度完全不同的药物的协同释放。
