载有地尔硫䓬树脂复合物的羧甲基黄原胶微球的研制初步研究
Preliminary investigation on the development of diltiazem resin complex loaded carboxymethyl xanthan beads.
作者信息
Ray Somasree, Maiti Sabyasachi, Sa Biswanath
机构信息
Gupta College of Technological Sciences, Ashram More, Asansol-1, India.
出版信息
AAPS PharmSciTech. 2008;9(1):295-301. doi: 10.1208/s12249-007-9012-x. Epub 2008 Jan 19.
The objective of this study was to develop a multiunit sustained release dosage form of diltiazem using a natural polymer from a completely aqueous environment. Diltiazem was complexed with resin and the resinate-loaded carboxymethyl xanthan (RCMX) beads were prepared by interacting sodium carboxymethyl xanthan (SCMX), a derivatized xanthan gum, with Al(+3) ions. The beads were evaluated for drug entrapment efficiency (DEE) and release characteristics in enzyme free simulated gastric fluid (SGF, HCl solution, pH 1.2) and simulated intestinal fluid (SIF, USP phosphate buffer solution, pH 6.8). Increase in gelation time from 5 to 20 min and AlCl(3) concentration from 1 to 3% decreased the DEE respectively from 95 to 79% and 88.5 to 84.6%. However, increase in gum concentration from 1.5 to 2.5% increased the DEE from 86.5 to 90.7%. The variation in DEE was related to displacement of drug from the resinate by the gel forming Al(+3) ions. While 75-82% drug was released in 2 h in SGF from various beads, 75 to 98% drug was released in 5 hour in SIF indicating the dependence of drug release on pH of dissolution media. Although the beads maintained their initial integrity throughout the dissolution process in both media, as evident from scanning electron microscopic studies, the faster release in SGF was accounted for higher swelling of the beads in SGF than in SIF. When release data (up to 60%) was fitted in power law expression, the drug release was found to be controlled by diffusion with simultaneous relaxation phenomena.
本研究的目的是在完全水性环境中使用天然聚合物开发一种地尔硫䓬多单元缓释剂型。地尔硫䓬与树脂络合,并通过使衍生化的黄原胶羧甲基黄原胶(SCMX)与Al(+3)离子相互作用制备载有树脂酸盐的羧甲基黄原胶(RCMX)微丸。对微丸进行了药物包封率(DEE)评估以及在无酶模拟胃液(SGF,HCl溶液,pH 1.2)和模拟肠液(SIF,USP磷酸盐缓冲溶液,pH 6.8)中的释放特性研究。胶凝时间从5分钟增加到20分钟以及AlCl(3)浓度从1%增加到3%分别使DEE从95%降至79%以及从88.5%降至84.6%。然而,胶浓度从1.5%增加到2.5%使DEE从86.5%增加到90.7%。DEE的变化与形成凝胶的Al(+3)离子将药物从树脂酸盐中置换出来有关。虽然在SGF中各种微丸在2小时内释放了75 - 82%的药物,但在SIF中5小时内释放了75%至98%的药物,这表明药物释放依赖于溶解介质的pH值。尽管从扫描电子显微镜研究可以明显看出,微丸在两种介质的整个溶解过程中都保持了其初始完整性,但在SGF中更快的释放是由于微丸在SGF中比在SIF中具有更高的溶胀度。当将释放数据(高达60%)拟合到幂律表达式时,发现药物释放受扩散和同时存在的松弛现象控制。
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