Impact of Hot-Melt Extrusion Processing Conditions on Physicochemical Properties of Amorphous Solid Dispersions Containing Thermally Labile Acrylic Copolymer

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22340%2F20%3A43918285" target="_blank" >RIV/60461373:22340/20:43918285 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/abs/pii/S0022354919306392?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/abs/pii/S0022354919306392?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.xphs.2019.10.005" target="_blank" >10.1016/j.xphs.2019.10.005</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Impact of Hot-Melt Extrusion Processing Conditions on Physicochemical Properties of Amorphous Solid Dispersions Containing Thermally Labile Acrylic Copolymer

Popis výsledku v původním jazyce

For successful formulation of amorphous solid dispersions (ASDs) using hot-melt extrusion, it is imperative to understand the effect that heat and shear rate has on the physicochemical properties of the excipient. In this study, we investigated the influence of hot-melt extrusion parameters on solvent-free binary ASDs of ibuprofen (IBU), a model active pharmaceutical ingredient, in methacrylic acid-ethyl acrylate copolymer type A, 1:1, EUDRAGIT® L100-55 (EUD). To evaluate the impact of barrel temperature, screw speed, and residence time on EUD mass average molar mass and IBU release profile, size-exclusion chromatography and dissolution testing were used, respectively. The optimal conditions were established for IBU loadings less than 40 wt. %. For ASD formulations prepared using the ideal variables, spectral and thermal analyses confirmed that, under dry conditions at a temperature of 25°C, IBU remained amorphous during an 18-month storage period. After 28 months, formulations with active pharmaceutical ingredient content above 30 wt. % started to recrystallize. A temperature–composition phase diagram, constructed using melting point depression and glass-transition temperature measurements of IBU–EUD mixtures, correlated well with the long-term physical stability. The effect that minor-to-moderate polymer degradation within the extrudates has on their long-term physical stability and dissolution characteristics is analyzed and discussed. © 2019 American Pharmacists Association®

Název v anglickém jazyce

Impact of Hot-Melt Extrusion Processing Conditions on Physicochemical Properties of Amorphous Solid Dispersions Containing Thermally Labile Acrylic Copolymer

Popis výsledku anglicky

For successful formulation of amorphous solid dispersions (ASDs) using hot-melt extrusion, it is imperative to understand the effect that heat and shear rate has on the physicochemical properties of the excipient. In this study, we investigated the influence of hot-melt extrusion parameters on solvent-free binary ASDs of ibuprofen (IBU), a model active pharmaceutical ingredient, in methacrylic acid-ethyl acrylate copolymer type A, 1:1, EUDRAGIT® L100-55 (EUD). To evaluate the impact of barrel temperature, screw speed, and residence time on EUD mass average molar mass and IBU release profile, size-exclusion chromatography and dissolution testing were used, respectively. The optimal conditions were established for IBU loadings less than 40 wt. %. For ASD formulations prepared using the ideal variables, spectral and thermal analyses confirmed that, under dry conditions at a temperature of 25°C, IBU remained amorphous during an 18-month storage period. After 28 months, formulations with active pharmaceutical ingredient content above 30 wt. % started to recrystallize. A temperature–composition phase diagram, constructed using melting point depression and glass-transition temperature measurements of IBU–EUD mixtures, correlated well with the long-term physical stability. The effect that minor-to-moderate polymer degradation within the extrudates has on their long-term physical stability and dissolution characteristics is analyzed and discussed. © 2019 American Pharmacists Association®

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

Journal of Pharmaceutical Sciences

ISSN

0022-3549

e-ISSN

—

Svazek periodika

109

Číslo periodika v rámci svazku

2

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

12

Strana od-do

1008-1019

Kód UT WoS článku

000507938800012

EID výsledku v databázi Scopus

2-s2.0-85074401120