Comparative Study of DSC-Based Protocols for API-Polymer Solubility Determination

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22340%2F21%3A43922293" target="_blank" >RIV/60461373:22340/21:43922293 - isvavai.cz</a>

Result on the web

<a href="https://pubs.acs.org/doi/abs/10.1021/acs.molpharmaceut.0c01232" target="_blank" >https://pubs.acs.org/doi/abs/10.1021/acs.molpharmaceut.0c01232</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.molpharmaceut.0c01232" target="_blank" >10.1021/acs.molpharmaceut.0c01232</a>

Result language

angličtina

Original language name

Comparative Study of DSC-Based Protocols for API-Polymer Solubility Determination

Original language description

Knowledge of the active pharmaceutical ingredient (API) solubility in a polymer is imperative for successful amorphous solid dispersion design and formulation but acquiring this information at storage temperature is challenging. Various solubility determination methods have been established, which utilize differential scanning calorimetry (DSC). In this work, three commonly used DSC-based protocols [i.e., melting point depression (MPD), recrystallization, and zero-enthalpy extrapolation (Z-EE)] and a method that we have developed called &quot;step-wise dissolution&quot;(S-WD) were analyzed. For temperature-composition phase diagram construction, two glass-transition temperature equations (i.e., those of Gordon-Taylor and Kwei) and three solid-liquid equilibrium curve modeling approaches [i.e., the Flory-Huggins model, an empirical equation, and the perturbed-chain statistical associating fluid theory (PC-SAFT) equation of state (EOS)] were considered. Indomethacin (IND) and Kollidon 12 PF (PVP K12) were selected as the API and polymer, respectively. An annealing time investigation revealed that the IND-PVP K12 dissolution process was remarkably faster than demixing, which contradicted previously published statements. Thus, the recrystallization method overestimated the solubility of IND in PVP K12 when a 2-h time of annealing was set as the benchmark. Likewise, the MPD and Z-EE methods overestimated the API solubility because of unreliable IND melting endotherm evaluation at lower API loadings and a relatively slow heating rate, respectively. When the experimental results obtained using the S-WD method (in conjunction with the Kwei equation) were applied to the PC-SAFT EOS, which was regarded as the most reliable combination, the predicted IND solubility in PVP K12 at T = 25 °C was approximately 40 wt %. When applicable, the S-WD method offers the advantage of using a limited number of DSC sample pans and API-polymer physical mixture compositions, which is both cost- and time-effective. © 2021 American Chemical Society.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10403 - Physical chemistry

Project

<a href="/en/project/GA19-02889S" target="_blank" >GA19-02889S: Stability of amorphous solid dispersions: Predictions by SAFT equations of state and their experimental verification</a><br>

Continuities

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

Publication year

2021

Confidentiality

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

Name of the periodical

Molecular Pharmaceutics

ISSN

1543-8384

e-ISSN

—

Volume of the periodical

18

Issue of the periodical within the volume

4

Country of publishing house

US - UNITED STATES

Number of pages

16

Pages from-to

1742-1757

UT code for WoS article

000637870700022

EID of the result in the Scopus database

2-s2.0-85103429680