用于地尔硫卓缓释的聚乙烯亚胺处理海藻酸钙珠的研制与评价
Development and evaluation of polyethyleneimine-treated calcium alginate beads for sustained release of diltiazem.
作者信息
Halder A, Mukherjee S, Sa B
机构信息
Jadavpur University, Kolkata, India.
出版信息
J Microencapsul. 2005 Feb;22(1):67-80. doi: 10.1080/02652040500045003.
The objective of this investigation is to develop a multi-unit sustained release dosage form of a water soluble drug from a completely aqueous environment avoiding the use of any organic solvent. The drug was complexed with resin and calcium alginate or polyethyleneimine-treated calcium alginate beads loaded with the resinate were prepared by a ionic/polyelectrolyte complexation method. The effect of different formulation variables on the characteristics of the beads was investigated. Although the drug release from spherical and smooth-surfaced calcium alginate beads in both acidic and alkaline dissolution media were slower than those obtained from plain resinate, none of the variables were found to prolong the drug release considerably due to rapid swelling and disintegration of calcium alginate beads in alkaline medium. On the other hand, drug release from polyethyleneimine-treated calcium alginate beads in acidic medium did not increase appreciably following a burst release. However, in alkaline medium, the drug release was found to increase gradually and extend over a different period of time depending on the intensity of polyethyleneimine treatment. Scanning electron micrographs revealed the formation of a dense membrane around the resinate-loaded calcium alginate matrix. The membrane appeared to be responsible for reduced swelling and protracted disintegration of the beads resulting in slow release of the drug. The results indicate that sustained release of a water soluble drug from polyethyleneimine-treated calcium alginate beads could be achieved by adjusting the formulation variables.
本研究的目的是在完全水性环境中开发一种水溶性药物的多单元缓释剂型,避免使用任何有机溶剂。药物与树脂络合,并通过离子/聚电解质络合法制备负载有树脂酸盐的海藻酸钙或聚乙烯亚胺处理的海藻酸钙珠。研究了不同配方变量对珠粒特性的影响。尽管在酸性和碱性溶出介质中,球形且表面光滑的海藻酸钙珠的药物释放比普通树脂酸盐的药物释放慢,但由于海藻酸钙珠在碱性介质中迅速溶胀和崩解,未发现任何变量能显著延长药物释放。另一方面,聚乙烯亚胺处理的海藻酸钙珠在酸性介质中的药物释放在突释后没有明显增加。然而,在碱性介质中,药物释放被发现逐渐增加,并根据聚乙烯亚胺处理的强度在不同时间段内持续。扫描电子显微镜照片显示在负载树脂酸盐的海藻酸钙基质周围形成了致密膜。该膜似乎是导致珠粒溶胀减少和崩解延长从而使药物缓释的原因。结果表明,通过调整配方变量可以实现聚乙烯亚胺处理的海藻酸钙珠对水溶性药物的缓释。