Setty C Mallikarjuna, Sahoo Satya S, Sa Biswanath
Centre for Advanced Research in Pharmaceutical Sciences, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India.
Drug Dev Ind Pharm. 2005 May;31(4-5):435-46. doi: 10.1080/03639040500214647.
Furosemide-loaded calcium alginate (ALG), calcium alginate-polyethyleneimine (ALG-PEI) and alginate-coated ALG-PEI (ALG-PEI-ALG) beads were prepared by ionotropic/polyelectrolyte complexation method to achieve controlled release of the drug. Effects of several formulation factors on the characteristics of the beads were investigated. Although variation in formulation factors did not influence the drug-loading efficiency (DLE) of ALG beads, rapid release of the drug in simulated intestinal fluid (SIF) could not be prevented. PEI treatment of ALG beads, however, prolonged the drug release considerably. Ionic interaction, as appeared from FTIR studies, between alginate and PEI led to the formation of polyelectrolyte complex membrane, the thickness of which was dependent on the conditions of PEI treatment as demonstrated by scanning electron microscopy (SEM). The membrane acted as a physical barrier to drug release from ALG-PEI beads. Alginate coating of ALG-PEI beads further prolonged the release of the drug by increasing membrane thickness and reducing swelling of the beads possibly by blocking the surface pores. Differential scanning calorimetry (DSC) study indicated that drug was not degraded by PEI treatment. The release data from ALG-PEI beads showed a good fit in power law expression, whereas the release data from ALG-PEI-ALG beads were found to fit in modified power law expression, and the mechanism of drug release changed from super case II transport to nearly Fickian transport, depending on the degree of gelation and formation of polyelectrolyte complex membrane.
通过离子otropic/聚电解质络合法制备了负载速尿的海藻酸钙（ALG）、海藻酸钙-聚乙烯亚胺（ALG-PEI）和海藻酸盐包衣的ALG-PEI（ALG-PEI-ALG）微球，以实现药物的控释。研究了几种制剂因素对微球特性的影响。虽然制剂因素的变化不影响ALG微球的载药效率（DLE），但无法阻止药物在模拟肠液（SIF）中的快速释放。然而，对ALG微球进行PEI处理可显著延长药物释放时间。FTIR研究表明，海藻酸盐和PEI之间的离子相互作用导致形成聚电解质复合膜，扫描电子显微镜（SEM）显示其厚度取决于PEI处理条件。该膜作为ALG-PEI微球药物释放的物理屏障。ALG-PEI微球的海藻酸盐包衣通过增加膜厚度和可能通过堵塞表面孔隙减少微球膨胀，进一步延长了药物释放时间。差示扫描量热法（DSC）研究表明，PEI处理不会使药物降解。ALG-PEI微球的释放数据与幂律表达式拟合良好，而ALG-PEI-ALG微球的释放数据则符合修正的幂律表达式，药物释放机制从超Ⅱ型转运转变为近菲克型转运，这取决于凝胶化程度和聚电解质复合膜的形成。
