Purpose

When establishing IVIVC, a special problem arises by interpretation of averaged in vivo profiles insight of considerable individual variations in term of time and number of mechanical stress events in GI-tract. The objective of the study was to investigate and forecast the effect of mechanical stress on in vivo behavior in human of hydrophilic matrix tablets.

Methods

Dissolution profiles for the marketed products were obtained at different conditions (stirring speed, single- or repeatable mechanical stress applied) and convoluted into C-t profiles. Vice versa, published in vivo C-t profiles of the products were deconvoluted into absorption profiles and compared with dissolution profiles by similarity factor.

Results

Investigated hydrophilic matrix tablets varied in term of their resistance against hydrodynamic stress or single stress during the dissolution. Different scenarios, including repeatable mechanical stress, were investigated on mostly prone Seroquel® XR 50 mg. None of the particular scenarios fits to the published in vivo C-t profile of Seroquel® XR 50 mg representing, however, the average of individual profiles related to scenarios differing by number, frequency and time of contraction stress. When different scenarios were combined in different proportions, the profiles became closer to the original in vivo profile including a burst between 4 and 5 h, probably, due to stress-events in GI-tract.

Conclusion

For establishing IVIVC of oral dosage forms susceptible mechanical stress, a comparison of the deconvoluted individual in vivo profiles with in vitro profiles of different dissolution scenarios can be recommended.

中文翻译：

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考虑生物相关机械应力的IVIVC缓释亲水性基质片剂

目的

建立IVIVC时，通过解释平均体内分布情况得出的一个特殊问题，即在胃肠道中机械应激事件的时间和次数方面，个体差异很大。该研究的目的是调查和预测机械应力对亲水性基质片剂的人体体内行为的影响。

方法

在不同条件下（搅拌速度，施加单一或可重复的机械应力）获得市售产品的溶解曲线，并将其卷积为Ct曲线。反之亦然，在体内发表的产品的Ct分布图被解卷积为吸收分布图，并通过相似因子与溶出度图进行比较。

结果

研究的亲水性基质片剂在溶解过程中其对流体动力应力或单一应力的抵抗力各不相同。在大多数俯卧的Seroquel®XR 50 mg上研究了不同的情况，包括可重复的机械应力。每种特定情况均不符合公开的Seroquel®XR 50 mg体内Ct曲线，但代表与情景有关的各个曲线的平均值，其收缩压力的数量，频率和时间有所不同。当不同的场景以不同的比例组合时，轮廓可能更接近原始的体内轮廓，包括在4到5小时之间的爆发，这可能是由于胃肠道中的压力事件造成的。

结论

为了建立易受机械应力作用的口服剂型的IVIVC，建议将去卷积的个体体内概况与不同溶出度的体外概况进行比较。