Kumar Pramod, Singh Sanjay, Mishra Brahmeshwar
Department of Pharmaceutics, Institute of Technology, Banaras Hindu University, Varanasi-221005, U.P. India.
Acta Pharm. 2009 Mar;59(1):15-30. doi: 10.2478/v10007-009-0010-2.
Extended release formulation of tramadol hydrochloride (TRH) based on osmotic technology was developed and evaluated. Target release profile was selected and different variables were optimized to achieve it. Formulation variables such as the level of swellable polymer, plasticizer and the coat thickness of semipermeable membrane (SPM) were found to markedly affect drug release. TRH release was directly proportional to the levels of plasticizer but inversely proportional to the levels of swellable polymer and coat thickness of SPM. Drug release from developed formulations was independent of pH and agitation intensity but dependent on osmotic pressure of the release media. In vivo study was also performed on six healthy human volunteers and various pharmacokinetic parameters (cmax, tmax, AUC0-24, MRT) and relative bioavailability were calculated. The in vitro and in vivo results were compared with the performance of two commercial TRH tablets. The developed formulation provided more prolonged and controlled TRH release compared to the marketed formulation. In vitro-in vivo correlation (IVIVC) was analyzed according to the Wagner-Nelson method. The optimized formulation (batch IVB) exhibited good IVIV correlation (R = 0.9750). The manufacturing procedure was found to be reproducible and formulations were stable over 6 months of accelerated stability testing.
开发并评估了基于渗透技术的盐酸曲马多（TRH）缓释制剂。选择了目标释放曲线，并对不同变量进行了优化以实现该曲线。发现诸如可溶胀聚合物水平、增塑剂和半透膜（SPM）包衣厚度等制剂变量对药物释放有显著影响。TRH释放与增塑剂水平成正比，但与可溶胀聚合物水平和SPM包衣厚度成反比。所开发制剂的药物释放与pH值和搅拌强度无关，但取决于释放介质的渗透压。还对六名健康人类志愿者进行了体内研究，并计算了各种药代动力学参数（cmax、tmax、AUC0-24、MRT）和相对生物利用度。将体外和体内结果与两种市售TRH片剂的性能进行了比较。与市售制剂相比，所开发的制剂提供了更长时间且可控的TRH释放。根据Wagner-Nelson方法分析了体外-体内相关性（IVIVC）。优化后的制剂（IVB批次）表现出良好的IVIV相关性（R = 0.9750）。发现制造工艺具有可重复性，并且制剂在6个月的加速稳定性测试中保持稳定。
