Wang Chao, Chen Fei, Li Ji-zhong, Tang Hai, Li Xiang, Yan Ke-shu, Ye Guan-hao, Pan Wei-san
Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning, PR China.
Yakugaku Zasshi. 2008 May;128(5):773-82. doi: 10.1248/yakushi.128.773.
A novel elementary osmotic pump tablet was developed. The system uses the core of drug-resin complexes (DRCs) loaded with propranolol hydrochloride (PNH) for time-controlled delivery. In traditional osmotic pump tablets (OPTs), the lag time was always minimized. However, in the DRCs osmotic pump tablet (DRCOPT), the lag time was increased to achieve the time-controlled delivery. The quantity of osmotic agent in the core and channeling agent in the coating solution as well as weight gain were confirmed to be essential for the release behavior. A spherical symmetric design was applied to the optimization of the DRCOPT. The optimal formulation mainly consisted of DRC 100 mg, polyethyleneoxide (N80) 182 mg, and NaCl 30 mg. The ratio of cellulose acetate (CA)/polyethylene glycol 4000 was 15:3 (w/w) in coating solution, and the weight gain was 8%. The release behavior of the optimal DRCOPT was evaluated in media with different pH, rotation speeds, and ionic strength. It was found to generate a 2-h lag time, to deliver PNH at a rate of zero order from 2 h to 14 h in the medium of NaCl 0.15 mol/l, and the cumulative release at 24 h was 94%. Drug relee was independent of pH and rotation speed, but was proportional to ionic strength. In summary, the lag time could be used in therapeutic regimens with the characteristics of chronotherapy because of the lag time and provides a new concept for the development of osmotic pumps.
研发了一种新型的基本渗透泵片。该系统使用负载盐酸普萘洛尔（PNH）的药物 - 树脂复合物（DRCs）核心进行定时释放。在传统渗透泵片（OPTs）中，滞后时间总是被最小化。然而，在DRCs渗透泵片（DRCOPT）中，滞后时间被延长以实现定时释放。已证实核心中的渗透剂数量、包衣溶液中的通道剂以及重量增加对释放行为至关重要。对DRCOPT的优化采用了球对称设计。最佳配方主要由100 mg DRC、182 mg聚环氧乙烷（N80）和30 mg NaCl组成。包衣溶液中醋酸纤维素（CA）/聚乙二醇4000的比例为15:3（w/w），重量增加为8%。在不同pH、转速和离子强度的介质中评估了最佳DRCOPT的释放行为。发现其产生2小时的滞后时间，在0.15 mol/l NaCl介质中从2小时到14小时以零级速率释放PNH，24小时的累积释放率为94%。药物释放与pH和转速无关，但与离子强度成正比。总之，由于滞后时间，该滞后时间可用于具有时辰治疗特征的治疗方案中，并为渗透泵的开发提供了一个新概念。
