API solubility in semi-crystalline polymer: Kinetic and thermodynamic phase behavior of PVA-based solid dispersions

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22340%2F22%3A43924992" target="_blank" >RIV/60461373:22340/22:43924992 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S0378517322004100" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0378517322004100</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ijpharm.2022.121855" target="_blank" >10.1016/j.ijpharm.2022.121855</a>

Jazyk výsledku

angličtina

Název v původním jazyce

API solubility in semi-crystalline polymer: Kinetic and thermodynamic phase behavior of PVA-based solid dispersions

Popis výsledku v původním jazyce

The formulation of amorphous solid dispersions (ASDs) represents a promising strategy for improving the poor bioavailability of many active pharmaceutical ingredients (APIs). The objective of this study was to investigate and compare the long-term physical stability (LTPS) of polyvinyl alcohol (PVA)-based solid dispersions formulated via hot-melt extrusion (HME) with their respective API–PVA temperature–composition (T–C) phase diagram. Furthermore, the impact of API glass-forming ability (GFA) on the LTPS was evaluated through the selection of two APIs with contrasting GFA (i.e., indomethacin (IND; good GFA) and naproxen (NAP; poor GFA)). Even though the predicted solubility of both APIs in PVA was less than 1 wt% at T = 25 °C, IND remained fully amorphous in HME-formulated IND–PVA extrudates with initial API loadings of 50, 40, and 30 wt% after a 24-month storage period. Meanwhile, NAP recrystallized to a considerable degree in each analogous sample with an amorphous NAP content of 22.5–23.5 wt% remaining after a 12-month storage period. While the constructed T–C phase diagrams were still in agreement with their respective LTPS study, they did not account for the impact of water uptake as well as potential HME-induced effects on the extrudate glass-transition temperature. This work may serve as a useful reference point for researchers who are interested in determining the solubility of an API in a semi-crystalline polymer and the challenges therein. © 2022 Elsevier B.V.

Název v anglickém jazyce

API solubility in semi-crystalline polymer: Kinetic and thermodynamic phase behavior of PVA-based solid dispersions

Popis výsledku anglicky

The formulation of amorphous solid dispersions (ASDs) represents a promising strategy for improving the poor bioavailability of many active pharmaceutical ingredients (APIs). The objective of this study was to investigate and compare the long-term physical stability (LTPS) of polyvinyl alcohol (PVA)-based solid dispersions formulated via hot-melt extrusion (HME) with their respective API–PVA temperature–composition (T–C) phase diagram. Furthermore, the impact of API glass-forming ability (GFA) on the LTPS was evaluated through the selection of two APIs with contrasting GFA (i.e., indomethacin (IND; good GFA) and naproxen (NAP; poor GFA)). Even though the predicted solubility of both APIs in PVA was less than 1 wt% at T = 25 °C, IND remained fully amorphous in HME-formulated IND–PVA extrudates with initial API loadings of 50, 40, and 30 wt% after a 24-month storage period. Meanwhile, NAP recrystallized to a considerable degree in each analogous sample with an amorphous NAP content of 22.5–23.5 wt% remaining after a 12-month storage period. While the constructed T–C phase diagrams were still in agreement with their respective LTPS study, they did not account for the impact of water uptake as well as potential HME-induced effects on the extrudate glass-transition temperature. This work may serve as a useful reference point for researchers who are interested in determining the solubility of an API in a semi-crystalline polymer and the challenges therein. © 2022 Elsevier B.V.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10404 - Polymer science

Projekt

<a href="/cs/project/GA22-07164S" target="_blank" >GA22-07164S: Racionální návrh systémů pro dodávání léčiv založených na laditelných biodegradabilních polymerech: iterativní in silico a experimentální postup</a><br>

Návaznosti

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

Rok uplatnění

2022

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

1873-3476

Svazek periodika

623

Číslo periodika v rámci svazku

červenec 2022

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

12

Strana od-do

121855

Kód UT WoS článku

000830017200004

EID výsledku v databázi Scopus

2-s2.0-85132941348