Conti S, Maggi L, Segale L, Ochoa Machiste E, Conte U, Grenier P, Vergnault G
Department of Pharmaceutical Chemistry, Via Taramelli, 12, I-27100 Pavia, Italy.
Int J Pharm. 2007 Mar 21;333(1-2):136-42. doi: 10.1016/j.ijpharm.2006.11.059. Epub 2006 Dec 12.
In this study hydroxypropylmethylcellulose (HPMC) and sodium carboxymethylcellulose (NaCMC) were used as polymeric carriers to improve controlled release performances of matrix tablets containing a soluble drug. The drug release behaviour of the systems containing these two polymers mixture and each material separately was investigated. To evaluate the effect of the dissolution medium pH, on the drug release performance, release tests were conducted at pH 1, 4.5 and 6.8. In vitro release studies demonstrated that the mixture of the two cellulose derivatives enables a better control of the drug release profiles at pH 4.5 and at 6.8 both in term of rate and mechanism. Texture analysis on the swollen tablets helps to understand drug release kinetic and mechanism. In fact, the results obtained confirm that a gel, which is characterized by high strength and consistence is less susceptible to erosion and chains disentanglement and the drug release mechanism is mainly governed by diffusion. On the contrary, gels, which show a low strength and texture, have low resistance to the fluid erosion action and the release of the active molecule is manly due to polymer relaxation and chains disentanglement moving the drug delivery kinetic towards an erosion/relaxation mechanism.
在本研究中,羟丙基甲基纤维素(HPMC)和羧甲基纤维素钠(NaCMC)被用作聚合物载体,以改善含可溶性药物的基质片剂的控释性能。研究了含有这两种聚合物混合物以及每种材料单独使用时系统的药物释放行为。为了评估溶出介质pH对药物释放性能的影响,在pH 1、4.5和6.8条件下进行了释放试验。体外释放研究表明,两种纤维素衍生物的混合物在pH 4.5和6.8时,无论在释放速率还是释放机制方面,都能更好地控制药物释放曲线。对溶胀片剂的质地分析有助于理解药物释放动力学和机制。事实上,所得结果证实,具有高强度和稠度特征的凝胶对侵蚀和链缠结的敏感性较低,药物释放机制主要受扩散控制。相反,强度和质地较低的凝胶对流体侵蚀作用的抵抗力较低,活性分子的释放主要是由于聚合物松弛和链缠结,使药物递送动力学朝着侵蚀/松弛机制发展。
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