一种茶碱时辰给药系统释药机制研究

 目的制备一种用于哮喘的夜间治疗的具有"慢速-快速"双相释药特征的茶碱时辰给药系统,并考察其释药机制。方法分别以磷酸钠和氯化钠为内外层渗透推动剂,制备双层片片芯(tablet-in-tablet core),并包以半透膜组成给药系统。考察包衣膜厚度对茶碱释放的影响及溶出过程中系统内微环境的变化过程。结果包衣膜在溶出过程中维持完整,包衣增重不影响系统双相释药的特征,增重范围控制在15～22mg·片^-1时该给药系统具有理想的释药曲线。释药过程中系统内部环境处于不断变化中,系统内渗透压由11000降低至4000mmol·L^-1,系统内pH值由7.0上升至11.2以上。结论本试验成功制备了一种具有"慢速-快速"双相释药特征的茶碱时辰给药系统,其释药受系统内微环境的渗透压及pH值调节。快速释药阶段系统微环境pH值升高,茶碱溶解度在此pH条件下增大,渗透压及增大的溶解度同时作用加速了茶碱释放。

Study on Drug Release Mechanism of Osmotic Pump Based Chronopharmaceutical Drug Delivery System for Theophylline

OBJECTIVE To develop a chronopharmaceutical drug delivery system with biphasic (smow-fast) theophylline release for the nocturnal therapy of asthma,and study the mechanism of the biphasic theophylline release. METHODS The developed system was composed of a tablet-in-tablet (TNT) core and a controlled porosity coating membrane.Sodium phosphate and sodium chloride were selected as the osmotic agent in inner and outer layer of the TNT core respectively.The influence of the coating membrane on drug release and the microenvironmental conditions in the system during the dissolution were studied. RESULTS Coating membrane maintained its integrity during dissolution. The biphasic drug release from the system was not influenced by the weight gain of the coating membrane. Satisfying biphasic release profile was obtained at a weight gain of 15～22 mg per tablet. Microenvironmental conditions were changed constantly during the dissolution. Microenvironmental osmotic pressure decreased from 11 000 to 4 000 mmol·L^-1,and microenvironmental pH increased from 7.0 to 11.2. CONCLUSION A chronopharmaceutical theophylline delivery system with biphasic (slow-fast) release profile was obtained in this study. Drug release from the system was controlled by microenvironmental osmotic pressure and microenvironmental pH in the system. At the second fast release stage,microenvironmental pH and the solubility of theophylline was increased. Theophylline release was accelerated by the increased theophylline solubility and microenvironmental osmotic pressure.