We evaluated the usefulness of quality control dissolution data collected with compendial Apparatus I and II, biorelevant dissolution data collected with compendial apparatus IV, and bioaccessibility data collected with the non-compendial tiny-TIM system in screening modified release formulations during the development of BCS Class I compounds using a Boehringer Ingelheim model experimental compound, A6197. Four products were investigated: an immediate release tablet, an extended release tablet, modified release mini-tablets, and extended release pellets. Data with modified release products collected with the compendial apparatus were evaluated vs. the average intraluminal dissolution estimated after deconvoluting clinical data collected in healthy adults. Data collected with the tiny-TIM system were evaluated vs. the average AUC and Cmax values estimated from the clinical data. Unlike with the quality control data collected with Apparatus I and II, data collected with Apparatus IV data and Level I biorelevant media adequately described the intraluminal dissolution process of the three modified release products. Data deviated less than 10% from the actual average deconvoluted intraluminal dissolution profiles, illustrating the usefulness of Apparatus IV biorelevant data in understanding the intraluminal dissolution process of BCS class I small molecules administered as modified release products in the fasted state. Total bioaccessibility data and maximum bioaccessibility data collected using the tiny-TIM and the immediate release tablet and the three modified release drug products correctly predicted the ranking of A6197 AUC values (R2=0.989) and Cmax values (R2=0.962), respectively, illustrating tiny-TIM as a useful system for formulation selection of BCS class I small molecules administered in the fasted state.

中文翻译：

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关于处方设置和tiny-TIM系统在评估禁食状态下具有各种释放曲线的口服药物产品的体内性能方面的有用性：案例示例A6197的钠盐。

我们评估了在BCS类的开发过程中，用附录I和II收集的质量控制溶出度数据，附录IV收集的与生物有关的溶出度数据和用非缩写tiny-TIM系统收集的生物可及性数据对筛选调释制剂的有用性。 I化合物使用勃林格殷格翰模型实验化合物A6197。研究了四种产品：速释片，缓释片，缓释微片和缓释微丸。将通过精简设备收集的调释产品的数据与在健康成人中收集的临床数据进行反卷积后估计的平均腔内溶出度进行比较。使用tiny-TIM系统收集的数据进行了评估。根据临床数据估算的平均AUC和Cmax值。与用仪器I和II收集的质量控制数据不同，用仪器IV数据和I级生物相关介质收集的数据充分描述了三种调释产品的腔内溶解过程。数据与实际平均去卷积的管腔内溶出度曲线的偏差小于10％，这说明了IV型生物相关数据在理解以禁食状态作为调释产品施用的BCS I类小分子的管腔溶出度过程中的有用性。使用tiny-TIM和速释片剂以及三种改良释放药物产品收集的总生物可及性数据和最大生物可及性数据正确预测了A6197 AUC值的排名（R2 = 0。