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

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10403 - Physical chemistry

Projekt

<a href="/cs/project/GA19-02889S" target="_blank" >GA19-02889S: Stabilita amorfních pevných disperzí: Predikce pomocí stavových rovnic SAFT a jejich experimentální ověření</a><br>

Návaznosti

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

Rok uplatnění

2020

Kód důvěrnosti údajů

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

Název periodika

International Journal of Pharmaceutics

ISSN

0378-5173

e-ISSN

—

Svazek periodika

589

Číslo periodika v rámci svazku

Neuveden

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

15

Strana od-do

"119845-1"-"119845-15"

Kód UT WoS článku

000580654300051

EID výsledku v databázi Scopus

2-s2.0-85091378432