IVIVC for Extended Release Hydrophilic Matrix Tablets in Consideration of Biorelevant Mechanical Stress
- PDF / 1,518,815 Bytes
- 10 Pages / 595.276 x 790.866 pts Page_size
- 32 Downloads / 169 Views
RESEARCH PAPER
IVIVC for Extended Release Hydrophilic Matrix Tablets in Consideration of Biorelevant Mechanical Stress Valentyn Mohylyuk 1,2 & Seyedreza Goldoozian 2 & Gavin P. Andrews 1 & Andriy Dashevskiy 2
Received: 17 July 2020 / Accepted: 28 September 2020 # The Author(s) 2020
ABSTRACT 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. * Andriy Dashevskiy [email protected] 1
Pharmaceutical Engineering Group, School of Pharmacy, Queen’s University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK
2
College of Pharmacy, Freie Universität Berlin, Kelchstrasse 31, 12169 Berlin, Germany
KEY WORDS extended release . gastrointestinal contraction . hydrophilic matrix tablet . IVIVC . pharmacokinetic profile
ABBREVIATIONS GI C-t IVIVC
Gastrointestinal Concentration-time In vitro - in vivo correlation
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. For example, an important and extensive cross-organization collaborative project involving multidisciplinary partners (OrBiTo) has examined important physicochemical properties of active pharmaceutical ingredients, in vitro characterization of drug formulations, characterization of in vivo behavior of compounds and formulations in GI-tract as well as in-silico models in developing oral dosage forms (1). Recently, the effect of si
Data Loading...
