Purely Predicting the Pharmaceutical Solubility: What to Expect from PC-SAFT and COSMO-RS?

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22340%2F22%3A43924910" target="_blank" >RIV/60461373:22340/22:43924910 - isvavai.cz</a>

Výsledek na webu

<a href="https://doi.org/10.1021/acs.molpharmaceut.2c00573" target="_blank" >https://doi.org/10.1021/acs.molpharmaceut.2c00573</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.molpharmaceut.2c00573" target="_blank" >10.1021/acs.molpharmaceut.2c00573</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Purely Predicting the Pharmaceutical Solubility: What to Expect from PC-SAFT and COSMO-RS?

Popis výsledku v původním jazyce

A pair of popular thermodynamic models for pharmaceutical applications, namely, the perturbed-chain statistical associating fluid theory (PC-SAFT) equation of state and the conductor-like screening model for real solvents (COSMO-RS) are thoroughly benchmarked for their performance in predicting the solubility of active pharmaceutical ingredients (APIs) in pure solvents. The ultimate goal is to provide an illustration of what to expect from these progressive frameworks when applied to the thermodynamic solubility of APIs based on activity coefficients in a purely predictive regime without specific experimental solubility data (the fusion properties of pure APIs were taken from experiments). While this kind of prediction represents the typical modus operandi of the first-principles-aided COSMO-RS, PC-SAFT is a relatively highly parametrized model that relies on experimental data, against which its pure-substance and binary interaction parameters (kij) are fitted. Therefore, to make this benchmark as fair as possible, we omitted any binary parameters of PC-SAFT (i.e., kij = 0 in all cases) and preferred pure-substance parameter sets for APIs not trained to experimental solubility data. This computational approach, together with a detailed assessment of the obtained solubility predictions against a large experimental data set, revealed that COSMO-RS convincingly outperformed PC-SAFT both qualitatively (i.e., COSMO-RS was better in solvent ranking) and quantitatively, even though the former is independent of both substance- and mixture-specific experimental data. Regarding quantitative comparison, COSMO-RS outperformed PC-SAFT for 9 of the 10 APIs and for 63% of the API-solvent systems, with root-mean-square deviations of the predicted data from the entire experimental data set being 0.82 and 1.44 log units, respectively. The results were further analyzed to expand the picture of the performance of both models with respect to the individual APIs and solvents. Interestingly, in many cases, both models were found to qualitatively incorrectly predict the direction of deviations from ideality. Furthermore, we examined how the solubility predictions from both models are sensitive to different API parametrizations. © 2022 American Chemical Society.

Název v anglickém jazyce

Purely Predicting the Pharmaceutical Solubility: What to Expect from PC-SAFT and COSMO-RS?

Popis výsledku anglicky

A pair of popular thermodynamic models for pharmaceutical applications, namely, the perturbed-chain statistical associating fluid theory (PC-SAFT) equation of state and the conductor-like screening model for real solvents (COSMO-RS) are thoroughly benchmarked for their performance in predicting the solubility of active pharmaceutical ingredients (APIs) in pure solvents. The ultimate goal is to provide an illustration of what to expect from these progressive frameworks when applied to the thermodynamic solubility of APIs based on activity coefficients in a purely predictive regime without specific experimental solubility data (the fusion properties of pure APIs were taken from experiments). While this kind of prediction represents the typical modus operandi of the first-principles-aided COSMO-RS, PC-SAFT is a relatively highly parametrized model that relies on experimental data, against which its pure-substance and binary interaction parameters (kij) are fitted. Therefore, to make this benchmark as fair as possible, we omitted any binary parameters of PC-SAFT (i.e., kij = 0 in all cases) and preferred pure-substance parameter sets for APIs not trained to experimental solubility data. This computational approach, together with a detailed assessment of the obtained solubility predictions against a large experimental data set, revealed that COSMO-RS convincingly outperformed PC-SAFT both qualitatively (i.e., COSMO-RS was better in solvent ranking) and quantitatively, even though the former is independent of both substance- and mixture-specific experimental data. Regarding quantitative comparison, COSMO-RS outperformed PC-SAFT for 9 of the 10 APIs and for 63% of the API-solvent systems, with root-mean-square deviations of the predicted data from the entire experimental data set being 0.82 and 1.44 log units, respectively. The results were further analyzed to expand the picture of the performance of both models with respect to the individual APIs and solvents. Interestingly, in many cases, both models were found to qualitatively incorrectly predict the direction of deviations from ideality. Furthermore, we examined how the solubility predictions from both models are sensitive to different API parametrizations. © 2022 American Chemical Society.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10403 - Physical chemistry

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

Molecular Pharmaceutics

ISSN

1543-8384

e-ISSN

1543-8392

Svazek periodika

19

Číslo periodika v rámci svazku

11

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

21

Strana od-do

4212-4232

Kód UT WoS článku

000860585400001

EID výsledku v databázi Scopus

2-s2.0-85138856543