Combining an In Vitro Kinetic Model with a Physiologically-Based Pharmacokinetic Model to Assess the Potential In Vivo Fate of Polyvinyl Pyrrolidone-Vinyl Acetate Copolymers

Pharmaceutical Research
Daniel S HsiehQi Gao

Abstract

To understand hydrolysis and alcoholysis of polyvinylpyrrolidone-co-vinylacetate (PVPVA) during formulation and storage, elucidate the reaction mechanism, establish an intrinsic kinetic model, and apply this model coupled with GastroPlus™ modeling to predict the amount of PVPVA degradation in vivo. The experimental approach includes the detection of the polymer reaction by solution nuclear magnetic resonance (NMR) and the measurement of reaction product concentration via gas chromatography (GC). The theoretical approach includes the establishment of the intrinsic kinetic model and the application of GastroPlus™ to predict the degree of PVPVA degradation. The kinetic model established is a first order reaction between PVPVA and 2-propanol (IPA) or water under an acidic condition. The application of this kinetic model shows that between 1.7 and 6.8 mg of degradant is formed in the GI tract for a 850 mg dose of PVPVA. The results from this application provide valuable input for process development and the risk analysis of the degradation of PVPVA.

References

Jun 9, 2005·Journal of Neurology·Umesh A BadrisingAxel R Wintzen
Nov 24, 2011·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Mohammed ManiruzzamanDennis Douroumis
Dec 18, 2014·Pharmaceutical Research·Daniel S HsiehMark Lindrud

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Methods Mentioned

BETA
NMR

Software Mentioned

KALETRA
Simulations Plus
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