Compatibility assessment of drug–poly(2-oxazoline) systems: COSMO-RS modeling and experimental validation

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22340%2F25%3A43932676" target="_blank" >RIV/60461373:22340/25:43932676 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S0014305725003544" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0014305725003544</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.eurpolymj.2025.114066" target="_blank" >10.1016/j.eurpolymj.2025.114066</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Compatibility assessment of drug–poly(2-oxazoline) systems: COSMO-RS modeling and experimental validation

Popis výsledku v původním jazyce

This study evaluates the compatibility of poly(2‑ethyl‑2‑oxazoline) (PEtOx) polymers with four active pharmaceutical ingredients (APIs) that have limited aqueous solubility—ibuprofen, indomethacin, naproxen, and paracetamol—through an integrated computational–experimental approach. Solid–liquid equilibrium (SLE) curves were predicted using the Conductor-like Screening Model for Real Solvents (COSMO‑RS), and validated against experimental solubility data obtained via differential scanning calorimetry (DSC) using the step-wise dissolution and melting enthalpy methods. Among the three tested PEtOx representations, the COSKF trimer model provided the best agreement with experimental results, effectively capturing key aspects of polymer flexibility and conformational behavior. The COSMO-RS predictions of SLE behavior demonstrated strong qualitative agreement—accurately reproducing solubility trends across the API–PEtOx binary systems—as well as satisfactory quantitative accuracy, with average deviations within acceptable margins. Sigma-profile analyses further supported the observed solubility behavior by revealing complementary polarity characteristics between the APIs and PEtOx. As the COSMO-RS approach is based entirely on molecular structure and intrinsic properties of the pure components—without requiring prior experimental data on their mixtures—it offers a practical and cost-effective tool for early-stage screening of API–poly(2-oxazoline) compatibility. These findings underscore the potential of combining COSMO-RS predictions with DSC-based solubility measurements to streamline formulation development and advance the design of polymer-based drug delivery systems.

Název v anglickém jazyce

Compatibility assessment of drug–poly(2-oxazoline) systems: COSMO-RS modeling and experimental validation

Popis výsledku anglicky

This study evaluates the compatibility of poly(2‑ethyl‑2‑oxazoline) (PEtOx) polymers with four active pharmaceutical ingredients (APIs) that have limited aqueous solubility—ibuprofen, indomethacin, naproxen, and paracetamol—through an integrated computational–experimental approach. Solid–liquid equilibrium (SLE) curves were predicted using the Conductor-like Screening Model for Real Solvents (COSMO‑RS), and validated against experimental solubility data obtained via differential scanning calorimetry (DSC) using the step-wise dissolution and melting enthalpy methods. Among the three tested PEtOx representations, the COSKF trimer model provided the best agreement with experimental results, effectively capturing key aspects of polymer flexibility and conformational behavior. The COSMO-RS predictions of SLE behavior demonstrated strong qualitative agreement—accurately reproducing solubility trends across the API–PEtOx binary systems—as well as satisfactory quantitative accuracy, with average deviations within acceptable margins. Sigma-profile analyses further supported the observed solubility behavior by revealing complementary polarity characteristics between the APIs and PEtOx. As the COSMO-RS approach is based entirely on molecular structure and intrinsic properties of the pure components—without requiring prior experimental data on their mixtures—it offers a practical and cost-effective tool for early-stage screening of API–poly(2-oxazoline) compatibility. These findings underscore the potential of combining COSMO-RS predictions with DSC-based solubility measurements to streamline formulation development and advance the design of polymer-based drug delivery systems.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10404 - Polymer science

Projekt

<a href="/cs/project/GA25-15646S" target="_blank" >GA25-15646S: Poly(2-oxazoliny): In silico úprava jejich vlastností pro vývoj lékově specifických systémů pro dodávání léčiv</a><br>

Návaznosti

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

Rok uplatnění

2025

Kód důvěrnosti údajů

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

Název periodika

EUROPEAN POLYMER JOURNAL

ISSN

0014-3057

e-ISSN

1873-1945

Svazek periodika

235

Číslo periodika v rámci svazku

červenec 2025

Stát vydavatele periodika

IE - Irsko

Počet stran výsledku

12

Strana od-do

114066

Kód UT WoS článku

001519906600001

EID výsledku v databázi Scopus

2-s2.0-105008492088