Structure and glass transition temperature of amorphous dispersions of model pharmaceuticals with nucleobases from molecular dynamics

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22340%2F21%3A43923028" target="_blank" >RIV/60461373:22340/21:43923028 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.mdpi.com/1999-4923/13/8/1253" target="_blank" >https://www.mdpi.com/1999-4923/13/8/1253</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/pharmaceutics13081253" target="_blank" >10.3390/pharmaceutics13081253</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Structure and glass transition temperature of amorphous dispersions of model pharmaceuticals with nucleobases from molecular dynamics

Popis výsledku v původním jazyce

Glass transition temperature (Tg) is an important material property, which predetermines the kinetic stability of amorphous solids. In the context of active pharmaceutical ingredients (API), there is motivation to maximize their Tg by forming amorphous mixtures with other chemicals, la-beled excipients. Molecular dynamics simulations are a natural computational tool to investigate the relationships between structure, dynamics, and cohesion of amorphous materials with an all-atom resolution. This work presents a computational study, addressing primarily the predictions of the glass transition temperatures of four selected API (carbamazepine, racemic ibuprofen, indo-methacin, and naproxen) with two nucleobases (adenine and cytosine). Since the classical non-po-larizable simulations fail to reach the quantitative accuracy of the predicted Tg, analyses of internal dynamics, hydrogen bonding, and cohesive forces in bulk phases of pure API and their mixtures with the nucleobases are performed to interpret the predicted trends. This manuscript reveals the method for a systematic search of beneficial pairs of API and excipients (with maximum Tg when mixed). Monitoring of transport and cohesive properties of API–excipients systems via molecular simulation will enable the design of such API formulations more efficiently in the future. © 2021 by the author. Licensee MDPI, Basel, Switzerland.

Název v anglickém jazyce

Structure and glass transition temperature of amorphous dispersions of model pharmaceuticals with nucleobases from molecular dynamics

Popis výsledku anglicky

Glass transition temperature (Tg) is an important material property, which predetermines the kinetic stability of amorphous solids. In the context of active pharmaceutical ingredients (API), there is motivation to maximize their Tg by forming amorphous mixtures with other chemicals, la-beled excipients. Molecular dynamics simulations are a natural computational tool to investigate the relationships between structure, dynamics, and cohesion of amorphous materials with an all-atom resolution. This work presents a computational study, addressing primarily the predictions of the glass transition temperatures of four selected API (carbamazepine, racemic ibuprofen, indo-methacin, and naproxen) with two nucleobases (adenine and cytosine). Since the classical non-po-larizable simulations fail to reach the quantitative accuracy of the predicted Tg, analyses of internal dynamics, hydrogen bonding, and cohesive forces in bulk phases of pure API and their mixtures with the nucleobases are performed to interpret the predicted trends. This manuscript reveals the method for a systematic search of beneficial pairs of API and excipients (with maximum Tg when mixed). Monitoring of transport and cohesive properties of API–excipients systems via molecular simulation will enable the design of such API formulations more efficiently in the future. © 2021 by the author. Licensee MDPI, Basel, Switzerland.

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

2021

Kód důvěrnosti údajů

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

Název periodika

PHARMACEUTICS

ISSN

1999-4923

e-ISSN

—

Svazek periodika

13

Číslo periodika v rámci svazku

8

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

14

Strana od-do

1253

Kód UT WoS článku

000690033300001

EID výsledku v databázi Scopus

2-s2.0-85113292646