IVIVC for Extended Release Hydrophilic Matrix Tablets in Consideration of Biorelevant Mechanical Stress

Valentyn Mohylyuk,Gavin P Andrews,Andriy Dashevskiy,Seyedreza Goldoozian

doi:10.1007/s11095-020-02940-7

Valentyn Mohylyuk, Gavin P Andrews + Show 2 more

Open Access

https://doi.org/10.1007/s11095-020-02940-7

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Abstract

PurposeWhen 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.MethodsDissolution 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.ResultsInvestigated 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.ConclusionFor 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.

Highlights

In addition to being used to understand oral bioavailability, in vitro - in vivo correlation (IVIVC) is being increasingly applied in the development of controlled release oral dosage forms
Since swellable/erodible hydrophilic tablets are considered as highly vulnerable to the mechanical stress, the objective of this study was to assess the effect of mechanical stress events in different dissolution scenarios and the impact that may have upon the prediction of in vivo profiles for different hydrophilic matrix tablets
For the discrimination of existing differences between particular dissolution profiles, the f2 factor seems to be more powerful than r2 – coefficient of determination (Table I), which is, mostly used for quantification of IVIVC [35]

Summary

Introduction

In addition to being used to understand oral bioavailability, in vitro - in vivo correlation (IVIVC) is being increasingly applied in the development of controlled release oral dosage forms. The effect of simulated GI-stress during dissolution from an extended release matrix tablet has been investigated using a specially adapted dissolution apparatus including different load cells [2,3,4,5,6,7,8], in-house dissolution testing apparatus [9,10,11], and periodical loading of dosage forms outside of the dissolution vessel [12,13]. The mechanical stress-events in the stomach and intestine can depend on many factors including individual physiological features, type of physical activity, lifestyle, and type of consumed food/drink [20]. The behavior of a non-disintegrating tablet in GI-tract is unique in terms of residence time in different parts of GI-tract, the effect of different media, agitation level and number and severity of stress-events

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