Use of biorelevant dissolution media in dissolution tests as a predictive method of oral bioavailability

Abstract Dissolution is a key step in the uptake of oral drugs. In order to compare the behaviour of the dissolution of two formulations, the dissolution profile test was used. This assay must be discriminative and should mimic in vivo conditions. Many dissolution media described in pharmacopoeias are not predictive of bioavailability. Due to this, biorelevant media are used as an alternative to solve this problem. The objective of this work is to evaluate the relevance of biorelevant dissolution media to predict in vivo drug dissolution. For this, a bibliographic search was carried out in scientific databases. The search was first performed for articles verifying the physicochemical properties of human gastrointestinal fluids. Subsequently, a comparison was made between the properties of gastrointestinal fluids and those of biorelevant and pharmacopoeial media. Finally, the results of bioequivalence studies and dissolution profile tests in biorelevant media described in the literature were compared. The results revealed that there are a few publications that have analysed some physicochemical properties of gastrointestinal fluids. In addition, high variability was observed for some properties. Regarding the comparison of these properties with pharmacopoeial media and biorelevant media, the analysis showed that the biorelevant media are more similar to gastrointestinal fluids than the pharmacopoeial media. Finally, the in vitro dissolution profile results were similar to the results obtained in vivo. Thus, biorelevant media may be useful for analysing dissolution profiles.

【摘要】溶出是口服药物吸收的关键步骤。为对比两种制剂的溶出行为，本研究采用溶出曲线试验。该检测方法需具备区分能力，且应模拟体内生理环境。药典所载的多种溶出介质无法预测药物的生物利用度，为此，生物相关介质（biorelevant media）作为替代方案被用于解决该问题。本研究旨在评估生物相关介质预测体内药物溶出的相关性。为此，研究人员在科学数据库中开展了文献检索工作：首先检索验证人体胃肠液理化性质的相关文献，随后对比胃肠液与生物相关介质及药典介质的各项性质，最后对文献中记载的、在生物相关介质中开展的生物等效性研究与溶出曲线试验的结果进行了对比。结果显示，仅有少量文献分析了胃肠液的部分理化性质，且部分性质存在较高的变异性。针对上述性质与药典介质及生物相关介质的对比分析表明，生物相关介质较药典介质更贴近胃肠液的固有特性。最终，体外溶出曲线结果与体内试验所得结果具有较高相似性，因此生物相关介质可用于药物溶出曲线的分析研究。