Purpose When establishing IVIVC, a special problem arises by interpretation of averagedin vivoprofiles 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 onin vivobehavior 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, publishedin vivoC-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 (R) XR 50 mg. None of the particular scenarios fits to the publishedin vivoC-t profile of Seroquel (R) 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 originalin vivoprofile 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 individualin vivoprofiles within vitroprofiles of different dissolution scenarios can be recommended.