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海藻酸钠与钙和铝离子进行原位交联以维持茶碱从聚合物基质中的释放。

In situ cross-linking of sodium alginate with calcium and aluminum ions to sustain the release of theophylline from polymeric matrices.

作者信息

Nokhodchi Ali, Tailor Anish

机构信息

Pharmacy Department, Kings College London, 150 Stamford Street, Franklin-Wilkins Building, London SE1 9NN, UK.

出版信息

Farmaco. 2004 Dec;59(12):999-1004. doi: 10.1016/j.farmac.2004.08.006.

Abstract

Small matrices of calcium alginate or aluminium alginate have been investigated as possible controlled release systems for drugs. The objective of the present study was to sustain the release of theophylline from alginate matrices using different concentrations of aluminium chloride and calcium chloride in presence and absence of HPMC. Tablets containing differing concentrations of aluminium and calcium chloride were produced and the release rate of theophylline was tested using the basket dissolution apparatus over 8 h. Increasing amounts of aluminium chloride from 0.0001 to 0.00068 moles decreased the release of theophylline from 95.1 +/- 0.27 to 29.5 +/- 1.5, indicating a significant effect of aluminium ions on a reduction in the release rate of theophylline from sodium alginate matrices. In the case of matrices containing different concentrations of calcium ions, as the concentration of calcium chloride increased, the release rate increased to an optimum then declined after this. This was due to insufficient calcium ions being available to cross-link with the sodium alginate to form an insoluble gel. The effect of aluminium ions, as this is a trivalent ion compared to calcium, which is a divalent ion, aluminium ions are able to decrease the release rate with a smaller concentration compared to calcium ions. The results also showed that the presence of HPMC caused a reduction in release rate of theophylline from alginate matrices containing calcium chloride. Whereas, in the case of alginate matrices containing aluminium chloride the release rate of theophylline increased in presence of HPMC. For comparing the dissolution data, dissolution efficiency (DE) was used. The values of DE are consistent with the dissolution data. The results show that within a formulation series, DE values generally decrease when the cation concentration increases and this criterion can be used to describe the effect of calcium and aluminium ions on the release behaviour of theophylline from polymeric matrices.

摘要

海藻酸钙或海藻酸铝的小基质已被研究作为药物的可能控释系统。本研究的目的是在有和没有羟丙基甲基纤维素(HPMC)的情况下,使用不同浓度的氯化铝和氯化钙来维持茶碱从海藻酸盐基质中的释放。制备了含有不同浓度氯化铝和氯化钙的片剂,并使用篮式溶出装置在8小时内测试了茶碱的释放速率。氯化铝的量从0.0001摩尔增加到0.00068摩尔,使茶碱的释放率从95.1±0.27降至29.5±1.5,表明铝离子对降低茶碱从海藻酸钠基质中的释放速率有显著影响。对于含有不同浓度钙离子的基质,随着氯化钙浓度的增加,释放速率先增加到最佳值,然后在此之后下降。这是由于没有足够的钙离子可用于与海藻酸钠交联形成不溶性凝胶。铝离子的作用,因为与二价离子钙相比它是三价离子,铝离子能够以比钙离子更低的浓度降低释放速率。结果还表明,HPMC的存在导致茶碱从含氯化钙的海藻酸盐基质中的释放速率降低而对于含有氯化铝的海藻酸盐基质,在HPMC存在下茶碱的释放速率增加。为了比较溶出数据,使用了溶出效率(DE)。DE值与溶出数据一致。结果表明,在一个制剂系列中,当阳离子浓度增加时,DE值通常会降低,并且该标准可用于描述钙和铝离子对茶碱从聚合物基质中释放行为的影响。

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