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Eur J Pharm Sci. 2019 Oct 1;138:105044. doi: 10.1016/j.ejps.2019.105044. Epub 2019 Aug 14.

A novel in vivo predictive dissolution testing coupled with a modeling and simulation for hydrogel matrix monolithic extended release oral dosage forms.

Author information

1
Pharmaceutical Research and Technology Labs, Astellas Pharma Inc., 180 Ozumi, Yaizu, Shizuoka 425-0072, Japan; Institute of Pharmaceutical Technology, Goethe University Frankfurt am Main, Max-von-Laue Straße 9, D-60438 Frankfurt am Main, Germany. Electronic address: atsushi.kambayashi@astellas.com.
2
Institute of Pharmaceutical Technology, Goethe University Frankfurt am Main, Max-von-Laue Straße 9, D-60438 Frankfurt am Main, Germany.

Abstract

The objective of this research was to design a novel in vitro dissolution testing for hydrogel matrix monolithic extended release tablets, in which physiologically relevant conditions of swelling, stress, and erosion for the tablets in the fasted gastrointestinal tract are taken into consideration. Mirabegron extended release tablets (three variations) were used as model formulations in this research. In in vitro dissolution testing, the tablets were allowed to swell in 10 mL of dissolution medium, after which they were stressed under a pressure of ca. 300 g/cm2 and then allowed to erode in a very limited volume of intestinal fluid. The drug release results from this in vitro test were coupled with in silico modeling and simulation to predict individual plasma concentration profiles after oral administration of the extended release tablets to beagle dogs. The results of the in silico simulations indicated that the proposed approach is able to predict in vivo performance of the hydrogel matrix monolithic extended release tablets in individualized simulations.

KEYWORDS:

Extended release; Hydrogel matrix formulations; In silico modeling and simulations; In vitro dissolution; Oral drug absorption; Sustained release

PMID:
31421255
DOI:
10.1016/j.ejps.2019.105044

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