Assessing the influence of media composition and ionic strength on drug release from commercial immediate-release and enteric-coated aspirin tablets
Assessing the influence of media composition and ionic strength on drug release from commercial immediate-release and enteric-coated aspirin tablets
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DOI：
10.1111/jphp.12777
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发表时间：
2017-10-01
影响因子：
3.3
通讯作者：
Klein, Sandra
中科院分区：
文献类型：
--
作者：
Karkossa, Frank;Klein, Sandra
目的 该测试系列的目的是阐明选择正确的介质成分对肠溶剂型进行生物预测体外溶出筛选的重要性。方法在具有不同 pH、电解质组成和离子强度的磷酸盐基和碳酸氢盐基介质中评估速释 (IR) 和肠溶 (EC) 阿司匹林制剂的药物释放。主要发现药物 阿司匹林速释片的释放不受介质成分的影响。相反，EC阿司匹林制剂的药物释放受到缓冲剂种类和离子强度的影响。在所有介质中，药物释放随着离子强度的增加而增加，但与基于磷酸盐的缓冲液相比，在基于碳酸氢盐的缓冲液中药物释放被延迟。有趣的是，溶出介质中的阳离子种类也对药物释放有明显影响。 Blank CarbSIF（一种模拟小肠液 pH 和平均离子组成的新型介质）中获得的药物释放曲线与所有其他研究的缓冲液组合物中获得的药物释放曲线不同。 结论 本研究系统地筛选了各种介质参数对 EC 阿司匹林制剂药物释放的影响，清楚地表明，在开发预测溶出测试时，模拟管腔内液体的离子组成非常重要 尽可能接近。
ObjectivesThe objective of this test series was to elucidate the importance of selecting the right media composition for a biopredictive in-vitro dissolution screening of enteric-coated dosage forms.MethodsDrug release from immediate-release (IR) and enteric-coated (EC) aspirin formulations was assessed in phosphate-based and bicarbonate-based media with different pH, electrolyte composition and ionic strength.Key findingsDrug release from aspirin IR tablets was unaffected by media composition. In contrast, drug release from EC aspirin formulations was affected by buffer species and ionic strength. In all media, drug release increased with increasing ionic strength, but in bicarbonate-based buffers was delayed when compared with that in phosphate-based buffers. Interestingly, the cation species in the dissolution medium had also a clear impact on drug release. Drug release profiles obtained in Blank CarbSIF, a new medium simulating pH and average ionic composition of small intestinal fluid, were different from those obtained in all other buffer compositions studied.ConclusionsResults from this study in which the impact of various media parameters on drug release of EC aspirin formulations was systematically screened clearly show that when developing predictive dissolution tests, it is important to simulate the ionic composition of intraluminal fluids as closely as possible.