A controlled porosity osmotic pump system with biphasic release of theophylline: Influence of weight gain on its in vivo pharmacokinetics

作者：Bi Yueqi; Zhang Yunyan; Zhao Junning; Mao Shengjun; Hou Shixiang^*

来源：Chemical & Pharmaceutical Bulletin, 2008, 56(6): 792-795.

DOI：10.1248/cpb.56.792

• controlled porosity osmotic pump
• biphasic release
• theophylline
• weight gain
• pharmacokinetics

In our previous work, a controlled porosity osmotic pump system with biphasic release of theophylline, a system composed of a tablet-in-tablet (TNT) core and a controlled porosity coating membrane, was developed for the nocturnal therapy of asthma. Sodium phosphate and sodium chloride were selected as the osmotic agents in inner and outer layer of the TNT core respectively, and CA-PEG400-DEP (54.5%-36.4%-9.1%, w/w) was chosen as coating solution. Formulations with weight gain of 19 mg/T (mg per tablet), 9 mg/T and 6 mg/T were prepared respectively and their pharmacokinetics in beagle dogs were also studied to examine the influence of weight gain on their in vivo pharmacokinetics. Sustained release tablet of theophylline (SRT) was selected as reference to evaluate the in vitro and in vivo difference between conventional sustained release tablets and the developed formulation. T(max) and mean residence time (MRT) of the developed formulations were prolonged compared to that of SRT and a satisfying bioavailability was achieved at weight gain of 6 mg/T. If applied to the chronotherapy of asthma at night, the developed formulation with a weight gain of 6 mg/T might help to reduce the inconvenience brought by too later administration of conventional dosage forms and maintain a relatively high blood drug concentration 7 h after administration.

• 出版日期2008-6
• 单位四川大学; 四川省中医药科学院