A controlled porosity osmotic pump system with biphasic release of theophylline

作者：Bi Yueqi; Mao Shengjun; Gan Liangchun; Li Yuanbo; Wang Changguang; Xu Nannan; Zheng Yu; Cheng Qiuhong; Hou Shixiang^*

来源：Chemical & Pharmaceutical Bulletin, 2007, 55(11): 1574-1580.

DOI：10.1248/cpb.55.1574

• controlled porosity osmotic pump
• biphasic release
• theophylline
• nocturnal asthma therapy
• drug release mechanism

A controlled porosity osmotic pump system with biphasic release of theophylline was developed for the nocturnal therapy of asthma. The developed system was composed of a tablet-in-tablet (TNT) core and a controlled porosity coating membrane. Release pattern of the developed system was influenced by amount of pore former (18.2-45.5%, w/w of polymer), weight gain (16-26 mg per tablet) of the coating membrane and osmotic agents used in inner layer of the TNT core. When sodium phosphate and sodium chloride were selected as the osmotic agents in inner and outer layer of the TNT core respectively, target release profile was obtained with coating solution cellulose acetate-polyethylene glycol 400-diethyl phthallate (54.5-36.4-9.1%, w/w) at a weight gain of 1622 mg per tablet. To examine the mechanism of drug release, release profiles of osmotic agents, micro-environmental osmotic pressure and micro-environmental pH of the formulation during dissolution were studied. Micro-environmental osmotic pressure decreased and micro-environmental pH increased continuously during the whole dissolution process, theophylline release was dominated by the successive dissolution of sodium chloride and sodium phosphate. Theophylline solubility increased as environmental pH exceeded 10.8. At the last stage of the biphasic release, micro-environmental pH in the developed formulation reached 10.9, and theophylline release was promoted by its elevated solubility despite of the decrease of micro-environmental osmotic pressure in the developed formulaiton.

• 出版日期2007-11
• 单位四川大学; 四川省中医药科学院