硫酸特布他林脉冲控释片的制备与释放机理研究硫酸特布他林脉冲控释片的制备与释放机理研究

目的制备硫酸特布他林双层包衣脉冲片，考察处方及释放条件对体外释药行为的影响，解析其释放机理。方法粉末直接压片法制备含渗透活性物质的片芯，滚转包衣锅法分别包溶胀层和控释衣层。通过测定释放度研究脉冲片的制剂学特征，并研究脉冲片的吸水动力学和膨胀行为。结果双层包衣片以脉冲形式释放，释药时滞随控释衣层厚度增加而延长，释药速度减小；渗透活性物质和溶胀层可提高快速释放期的释药速率。溶出介质pH值和搅拌速度对释药行为无影响。释药机理包括扩散、溶胀和渗透泵原理。结论调整控释衣膜厚度和组成可获得理想的脉冲释药行为，满足时辰治疗的要求。

Preperation of terbutaline sulphate pulsatile release tablet and mechanism elucidation

Aim To prepare terbutaline sulphate (TB) bi-layered pulsatile release tablets, evaluate the effects of the formulation and dissolution medium on drug release behavior, and to elucidate the mechanism of drug release based on obtained results. Methods Core tablets containing osmotic active agent were prepared by direct compression and spray coated with swelling layer and semipermeable membrane subsequently. Pharmaceutical properties of TB pulsatile tablets were investigated by dissolution test. The water uptake kinetics and swelling behavior of tablet were studied by the water uptake test and project enlargement method. Results TB released from bi-layered tablets in pulsatile behaviors. The lag-time was prolonged with the increase of coating level of semipermeable membrane and the steady release rate was increased significantly with the increase of osmotic active agent and swelling layer. It was shown that drug release behaviors were constant irrespective of various pH of dissolution medium and rotation speeds. All results indicated that diffusion, swelling and osmotic pumping were involved in the mechanism of drug release. Conclusion Ideal pulsed release behaviors can be achieved by adjusting the coating level and composition of semipermeable membrane to meet the requirement of chronotherapy.