盐酸克仑特罗双层缓释片的研制及体内外评价

Preparation and Evaluation in vivo and in vitro of Clenbuterol Hydrochloride Sustained-release Bilayer Tablets

关键词:  盐酸克仑特罗  双层缓释片  体内外相关性

Key words:  clenbuterol Hydrochloride  sustained-release bilayer tablets  in vitro and in vivo correlation

摘要:

目的研制盐酸克仑特罗缓释双层片并考察其体外释放及犬体内药动学。方法以羟丙甲纤维素和乙基纤维素为骨架材料，分别采用粉末直接压片和湿法制粒技术制备盐酸克仑特罗双层缓释片。测定其体外释放度和Beagle犬口服单剂量盐酸克仑特罗普通片和双层缓释片后血浆中药物的浓度，推算药动学参数。结果盐酸克仑特罗双层缓释片体外释放符合Higuchi方程。盐酸克仑特罗双层缓释片和普通片的有关药动学参数如下：t1/2分别为(11.90±1.42)，(6.18±0.81) h；Cmax为(5.86±0.33)，(11.43±0.64)ng·mL-1；tmax为(3.17±0.73)，(2.02±0.35) h；AUC0～t为(65.08±2.63)，(68.00±2.89)ng·h·mL-1。结论盐酸克仑特罗双层缓释片体外具有明显的速释和缓释特性。体内平均滞留时间长于普通片。体外释放和体内吸收有良好的相关性。

Abstract:

OBJECTIVE To prepare clenbuterol hydrochloride sustained-release bilayer tablets and study its pharmaceutical characteristics in vivo and in vitro. METHODS HPMC and EC mixed matrix were used to prepare clenbuterol hydrochloride sustained-release bilayer tablets by direct compression technique and wet granulation technique. The release characteristics in vitro and pharmacokinetics in dogs of clenbuterol hydrochloride sustained-release bilayer tablets were investigated.RESULTS The drug dissolution of sustained-release bilayer tablets was consistent with Higuchi equation. The peak levels (Cmax) after administration of sustained-release bilayer tablets and reference tablets were (5.86±0.33) and (11.43±0.64) ng·mL-1 at (3.17±0.73) and (2.02±0.35) h, respectively. The mean elimination half lives (t1/2) were found to be (11.90±1.42) and (6.18±0.81) h, respectively. AUC0-t were calculated to be (65.08±2.63) and (68.00±2.89) ng·h·mL-1, respectively.CONCLUSION The clenbuterol hydrochloride sustained-release bilayer tablets exhibited both sustained-and rapid-release characteristics in vitro. The calculated MRT of sustained-release bilayer tablets was significantly more than that of reference tablets. There existed correlation between thein vitro release and in vivo absorption.