Efentakis M, Koutlis A
University of Athens, School of Pharmacy, Department of Pharmaceutical Technology, Panepistimiopolis 15771, Athens, Greece.
Pharm Dev Technol. 2001;6(1):91-8. doi: 10.1081/pdt-100000048.
The release characteristics and the effect of viscosity of sodium alginate on the release rate of furosemide (a rather poorly soluble drug) from hard gelatin capsules (single-unit), and minitablets (multiple-unit) filled in hard gelatin capsules, were evaluated. Swelling and erosion experiments showed a different behavior for each viscosity grade. Polymer characteristics influenced significantly the release of the drug from the preparations prepared and tested. The results indicate that erosion plays a significant role, accelerates release rate and shortens duration of drug release. Low viscosity formulations exhibited a greater erosion, and drug release was completed in 4 hours. Medium viscosity formulations showed intermediate erosion, while high viscosity formulations exhibited less erosion, and drug release was completed in 8 hours. The minitablets always displayed lower release and dissolution efficiency values than the capsules, and as the viscosity increased, the difference of dissolution efficiency between the two formulations increased accordingly. The results further indicated that the multiple-unit system demonstrated a more pronounced sustained effect than the single-unit, and therefore, it is a more suitable preparation for sustained release delivery of poorly soluble drugs. Analysis of release data indicate a rather zero-order release mechanism, which may be attributed mainly to swelling and an erosion/dissolution process.
评估了海藻酸钠的释放特性及其粘度对速尿(一种难溶性药物)从硬明胶胶囊(单单元)以及填充于硬明胶胶囊中的微型片(多单元)中释放速率的影响。溶胀和侵蚀实验表明不同粘度等级呈现出不同的行为。聚合物特性对所制备和测试制剂中药物的释放有显著影响。结果表明侵蚀起显著作用,加速了释放速率并缩短了药物释放持续时间。低粘度制剂表现出更大的侵蚀,药物在4小时内释放完毕。中粘度制剂显示出中等程度的侵蚀,而高粘度制剂表现出较少的侵蚀,药物在8小时内释放完毕。微型片的释放和溶出效率值始终低于胶囊,并且随着粘度增加,两种制剂之间的溶出效率差异相应增大。结果进一步表明多单元系统比单单元系统表现出更显著的缓释效果,因此,它是难溶性药物缓释给药更合适的制剂。释放数据分析表明是一种相当接近零级的释放机制,这可能主要归因于溶胀以及侵蚀/溶解过程。