Physical stability of hydroxypropyl methylcellulose-based amorphous solid dispersions: Experimental and computational study

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22340%2F20%3A43920769" target="_blank" >RIV/60461373:22340/20:43920769 - isvavai.cz</a>

Result on the web

<a href="https://www.sciencedirect.com/science/article/pii/S0378517320308309" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0378517320308309</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ijpharm.2020.119845" target="_blank" >10.1016/j.ijpharm.2020.119845</a>

Result language

angličtina

Original language name

Physical stability of hydroxypropyl methylcellulose-based amorphous solid dispersions: Experimental and computational study

Original language description

The preparation of an amorphous solid dispersion (ASD) is a promising strategy for improving the poor oral bioavailability of many active pharmaceutical ingredients (APIs). However, poor predictability of ASD long-term physical stability remains a prevalent problem. The purpose of this study was to evaluate and compare the predictive performance of selected models concerning solid-liquid equilibrium (SLE) curve and glass-transition temperature (T-g) line modeling of ibuprofen (IBU) in cellulosic polymers (i.e., hydroxypropyl methylcellulose (HPMC) and hydroxypropyl methylcellulose acetate succinate (HPMCAS)). For SLE curve modeling, an empirical analytical approach (Kyeremateng et al., 2014) and the Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT) equation of state (EOS) were chosen. Due to the unavailability of PC-SAFT parameters for both polymers, an approximation procedure for parametrization was applied. The Gordon-Taylor equation and Kwei equation were considered for T-g line determination. The impact of various computational set-ups (e.g., model parametrization or extrapolation length) on IBU solubility prediction at storage conditions was thoroughly investigated, assessed and confronted with the results from an 18-month physical stability study. IBU developed stable 20 wt% API content ASDs with both HPMC and HPMCAS. The extrapolation behavior and subsequent ASD thermodynamic stability prediction at storage conditions deduced from the aforementioned models were significantly different. Overall, the PC-SAFT EOS predicted higher IBU solubility in both polymers and, thus, a lower recrystallization tendency when compared to the empirical analytical approach. At higher IBU concentrations, liquid-liquid demixing in IBU-polymer systems was predicted by the PC-SAFT EOS, which was in qualitative disagreement with experimental observation.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10403 - Physical chemistry

Project

<a href="/en/project/GA19-02889S" target="_blank" >GA19-02889S: Stability of amorphous solid dispersions: Predictions by SAFT equations of state and their experimental verification</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2020

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

International Journal of Pharmaceutics

ISSN

0378-5173

e-ISSN

—

Volume of the periodical

589

Issue of the periodical within the volume

Neuveden

Country of publishing house

US - UNITED STATES

Number of pages

15

Pages from-to

"119845-1"-"119845-15"

UT code for WoS article

000580654300051

EID of the result in the Scopus database

2-s2.0-85091378432