Can Pure Predictions of Activity Coefficients from PC-SAFT Assist Drug-Polymer Compatibility Screening?
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22340%2F23%3A43928131" target="_blank" >RIV/60461373:22340/23:43928131 - isvavai.cz</a>
Result on the web
<a href="https://doi.org/10.1021/acs.molpharmaceut.3c00124" target="_blank" >https://doi.org/10.1021/acs.molpharmaceut.3c00124</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/acs.molpharmaceut.3c00124" target="_blank" >10.1021/acs.molpharmaceut.3c00124</a>
Alternative languages
Result language
angličtina
Original language name
Can Pure Predictions of Activity Coefficients from PC-SAFT Assist Drug-Polymer Compatibility Screening?
Original language description
The bioavailability of poorly water-soluble active pharmaceutical ingredients (APIs) can be improved via the formulation of an amorphous solid dispersion (ASD), where the API is incorporated into a suitable polymeric carrier. Optimal carriers that exhibit good compatibility (i.e., solubility and miscibility) with given APIs are typically identified through experimental means, which are routinely labor- and cost-inefficient. Therefore, the perturbed-chain statistical associating fluid theory (PC-SAFT) equation of state, a popular thermodynamic model in pharmaceutical applications, is examined in terms of its performance regarding the computational pure prediction of API-polymer compatibility based on activity coefficients (API fusion properties were taken from experiments) without any binary interaction parameters fitted to API-polymer experimental data (that is, kij = 0 in all cases). This kind of prediction does not need any experimental binary information and has been underreported in the literature so far, as the routine modeling strategy used in the majority of the existing PC-SAFT applications to ASDs comprised the use of nonzero kij values. The predictive performance of PC-SAFT was systematically and thoroughly evaluated against reliable experimental data for almost 40 API-polymer combinations. We also examined the effect of different sets of PC-SAFT parameters for APIs on compatibility predictions. Quantitatively, the total average error calculated over all systems was approximately 50% in the weight fraction solubility of APIs in polymers, regardless of the specific API parametrization. The magnitude of the error for individual systems was found to vary significantly from one system to another. Interestingly, the poorest results were obtained for systems with self-associating polymers such as poly(vinyl alcohol). Such polymers can form intramolecular hydrogen bonds, which are not accounted for in the PC-SAFT variant routinely applied to ASDs (i.e., that used in this work). However, the qualitative ranking of polymers with respect to their compatibility with a given API was reasonably predicted in many cases. It was also predicted correctly that some polymers always have better compatibility with the APIs than others. Finally, possible future routes to improve the cost-performance ratio of PC-SAFT in terms of parametrization are discussed. © 2023 The Authors. Published by American Chemical Society.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10403 - Physical chemistry
Result continuities
Project
<a href="/en/project/GA22-07164S" target="_blank" >GA22-07164S: Rational design of drug delivery systems based on tailored biodegradable polymers using an iterative in silico and experimental approach</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2023
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
MOLECULAR PHARMACEUTICS
ISSN
1543-8384
e-ISSN
1543-8392
Volume of the periodical
20
Issue of the periodical within the volume
8
Country of publishing house
US - UNITED STATES
Number of pages
15
Pages from-to
3960-3974
UT code for WoS article
001020628800001
EID of the result in the Scopus database
2-s2.0-85164835680