盐酸地尔硫棘缓释片的制备及Beagle犬体内药物代谢动力学研究

Preparation of sustained-release tablets of diltiazem hydrochloride and its pharmacokinetics in Beagle dogs

目的以聚氧乙烯(PEO)为骨架材料,制备盐酸地尔硫?缓释片,并对其进行Beagle犬体内药物代谢动力学研究。方法采用粉末直压片法制备盐酸地尔硫?缓释片,以市售盐酸地尔硫?缓释胶囊为参比,采用相似因子(f2)法对2种制剂体外释放曲线进行相似性评价,并进行生物等效性考察。结果盐酸地尔硫?缓释片与参比制剂体外溶出曲线相似;两者主要药物代谢动力学参数分别为AUC0~t(2009.1±969.5)和(1947.4±1098.8)ng·h·m L^(-1),Cmax(118.8±38.5)和(112.7±50.7)ng·m L^(-1),tmax(8.2±1.0)和(8.0±2.1)h;缓释片的平均相对生物利用度为(107.3±19.0)%。结论盐酸地尔硫?缓释片制备工艺简单,其在体内具有明显的缓释作用,与市售盐酸地尔硫?缓释胶囊生物等效。

Objective To prepare the sustained-release tablets of diltiazem hydrochloride（DH） with polyethylene oxides（PEO） as the matrix polymer and study its pharmacokinetics in Beagle dogs. Methods The sustained release tablets were fabricated by powder direct compression method. The marketed sustained-release capsules of DH were chosen as the reference preparation. The similarity factor（f2） was used to evaluate the similarity of release profiles of the 2 preparations. The bioequivalence of the test and the reference preparations was determined. Results The sustained-release tablets showed similar release profile to the reference preparation. Main pharmacokinetic parameters of sustained-release matrix tablets and reference preparation were obtained： AUC0 ~ t（2009.1±969.5） and（1947.4±1098.8） ng·h·m L^（-1）; Cmax（118.8±38.5） and（112.7±50.7） ng·m L^（-1）; tmax（8.2±1.0） and（8.0±2.1） h. The relative bioavailability of sustained-release tablets of the reference preparation was（107.3±19.0）%. Conclusion The sustained-release tablets of DH with simple manufacture process show obvious sustained-release characters in vivo, and are bioequivalent to the marketed sustained-release capsules of DH.