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水胶体基质的零级药物释放。

Zero-order drug release from hydrocolloid matrices.

作者信息

Möckel J E, Lippold B C

机构信息

Galenical Development, Boehringer Mannheim GmbH, Germany.

出版信息

Pharm Res. 1993 Jul;10(7):1066-70. doi: 10.1023/a:1018931210396.

Abstract

Matrices are manufactured by direct compression of a powder mixture of a polymer, e.g., methylhydroxypropyl cellulose (MHPC) or polyvinylalcohol (PVAI), and a drug. The following factors that can influence the drug release mode were investigated at constant surface: (i) polymer solution viscosity, glass transition temperature, and swelling; (ii) drug concentration in the matrix and solubility; and (iii) conditions of release experiment (hydrodynamics). In the case of zero-order release profiles (hydrocolloids with low viscosities), only the dissolution of the polymer appears to control the drug release rate. Factors accelerating polymer dissolution resulted in higher release rates. Comparison of swollen and dry hydrocolloid matrices shows that the duration and kinetics of drug release were not controlled by the swelling front moving into the dry polymer, and water penetration and relaxation were not rate controlling. Therefore, the glass transition temperature had no effect on drug release from these hydrocolloids. The higher the hydrodynamic stress exerted on the eroding hydrocolloid, the faster the resulting drug release as a result of accelerated polymer dissolution. With hydrocolloids of very high viscosity the polymer dissolution is slow, and drug release from the swollen gel appears to be controlled by diffusion according to kinetics of the Higuchi type.

摘要

基质是通过直接压制聚合物(如甲基羟丙基纤维素(MHPC)或聚乙烯醇(PVAI))与药物的粉末混合物制成的。在恒定表面积下,研究了以下可能影响药物释放模式的因素:(i)聚合物溶液粘度、玻璃化转变温度和溶胀;(ii)基质中药物浓度和溶解度;以及(iii)释放实验条件(流体动力学)。在零级释放曲线(低粘度水胶体)的情况下,似乎只有聚合物的溶解控制药物释放速率。加速聚合物溶解的因素导致更高的释放速率。对溶胀和干燥水胶体基质的比较表明,药物释放的持续时间和动力学不受溶胀前沿向干燥聚合物中移动的控制,水的渗透和松弛也不是速率控制因素。因此,玻璃化转变温度对这些水胶体的药物释放没有影响。施加在侵蚀性水胶体上的流体动力学应力越高,由于聚合物溶解加速,药物释放就越快。对于粘度非常高的水胶体,聚合物溶解缓慢,从溶胀凝胶中的药物释放似乎根据Higuchi型动力学受扩散控制。

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