Jeong Seong Hoon, Park Kinam
Department of Pharmaceutics & Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA.
Int J Pharm. 2008 Sep 1;361(1-2):26-32. doi: 10.1016/j.ijpharm.2008.05.006. Epub 2008 May 15.
Complexes of ion-exchange resins and dextromethorphan (DM), a model drug, were prepared using different methods including a batch and a column method with different functional groups, ion-exchange capacity, degree of crosslinking, and resin particle size. Drug loading efficiency, release profiles, and scanning electron micrographs were also investigated. Most of the functional groups of resins were loaded with DM after the completion of a double batch method and it was recommended for drug loading into the ion-exchange resin. Using a column method, drug loading could be monitored by simply measuring changes in the pH of the reaction medium since as complex formation reached completion, the pH returned to the initial pH of the eluent due to the limited amount of functional groups available for the exchange. DM could be loaded up to the ratio of 3 (drug): 1 (resin), depending on the physicochemical properties of the resin. As the crosslinking ratio and particle size increased, the drug loading and release rate decreased due to the reduced effective diffusion coefficient and surface area. Assuming that the resin particles are uniform spheres of radius r, release mechanism was evaluated using plots of a Bt-t relationship, where B (=pi(2)D(i)/r(2)) and t are the rate constant and time, respectively. D(i) represents the effective diffusion coefficient of DM inside the resin. The Bt-t plots displayed a straight line indicating that the diffusion of DM in the resin matrix is the rate-controlling step.
采用不同方法制备了离子交换树脂与模型药物右美沙芬（DM）的复合物，这些方法包括分批法和柱法，使用了具有不同官能团、离子交换容量、交联度和树脂粒径的材料。还研究了药物负载效率、释放曲线和扫描电子显微镜图像。在双批次法完成后，树脂的大多数官能团都负载了DM，推荐采用这种方法将药物负载到离子交换树脂中。使用柱法时，由于随着络合物形成完成，由于可用于交换的官能团数量有限，反应介质的pH值会回到洗脱液的初始pH值，因此通过简单测量反应介质的pH值变化就可以监测药物负载情况。根据树脂的物理化学性质，DM的负载比例可达3（药物）：1（树脂）。随着交联比和粒径的增加，由于有效扩散系数和表面积降低，药物负载和释放速率下降。假设树脂颗粒是半径为r的均匀球体，使用Bt - t关系图评估释放机制，其中B（=π²D(i)/r²）和t分别是速率常数和时间。D(i)表示DM在树脂内部的有效扩散系数。Bt - t图显示为一条直线，表明DM在树脂基质中的扩散是速率控制步骤。
