Brockmeier D, Dengler H J, Voegele D
Eur J Clin Pharmacol. 1985;28(3):291-300. doi: 10.1007/BF00543326.
Two principal approaches to demonstrating the continuous in vivo relevance of an in vitro dissolution test are outlined. The first uses the convolution technique to predict the concentration-time course in vivo; the second uses deconvolution as a mathematical tool to estimate the in vivo dissolution profile. The weighting function must be known to utilise either technique. Defined by the aim of the analysis the dose-normalized response to the oral solution is regarded as the weighting function (Impulse Response). In both cases the essential step is continuous comparison of the predicted time dependent data with actual readings of the same class. To permit the prediction of concentration-time data from in vitro dissolution data the basic equations for the transformation of the time base from in vitro to in vivo conditions are developed. The transformation is essential, since one cannot assume that the time scales for the in vitro and the in vivo experiment are definitely the same. The estimated in vivo dissolution profile using the deconvolution technique gives a hypothetical image of the true in vivo dissolution curve. Comparison with in vitro dissolution test results, using one of the equivalence testing procedures, reveals how closely and for how long the in vitro dissolution test simulates the in vivo dissolution process. For the formulation of theophylline studied, equivalence of the in vitro and the estimated in vivo dissolution profiles was not confirmed for the entire period of observation, but it was demonstrated for approximately the first 5 h. The later inequivalence is not due to possible non-linear or time-dependent kinetics of theophylline. There is a discussion of whether a change in pH, agitation of the formulation, diffusion conditions or the absorption rate constant along the gastrointestinal tract might explain the biphasic linear correlation of the in vitro and in vivo data observed.
概述了两种证明体外溶出试验在体内持续相关性的主要方法。第一种方法使用卷积技术预测体内的浓度-时间过程；第二种方法使用去卷积作为数学工具来估计体内溶出曲线。要使用这两种技术中的任何一种，都必须知道权重函数。根据分析目的定义，口服溶液的剂量归一化反应被视为权重函数（脉冲响应）。在这两种情况下，关键步骤都是将预测的随时间变化的数据与同一类别的实际读数进行持续比较。为了从体外溶出数据预测浓度-时间数据，推导了将时间基准从体外条件转换为体内条件的基本方程。这种转换至关重要，因为不能假定体外和体内实验的时间尺度肯定相同。使用去卷积技术估计的体内溶出曲线给出了真实体内溶出曲线的假设图像。使用等效性检验程序之一将其与体外溶出试验结果进行比较，可揭示体外溶出试验模拟体内溶出过程的紧密程度和持续时间。对于所研究的茶碱制剂，在整个观察期内未证实体外和估计的体内溶出曲线具有等效性，但在大约最初5小时内得到了证实。后期的不等效性并非由于茶碱可能的非线性或时间依赖性动力学。讨论了胃肠道pH值的变化、制剂的搅拌、扩散条件或吸收速率常数是否可以解释所观察到的体外和体内数据的双相线性相关性。
