Implications of Drug-Polymer Interactions on Time-Temperature-Transformation: A Tool to Assess the Crystallization Propensity in Amorphous Solid Dispersions.
Mol Pharm
; 20(3): 1806-1817, 2023 03 06.
Article
em En
| MEDLINE
| ID: mdl-36744878
ABSTRACT
The critical cooling rate (CRcrit) to prevent drug crystallization during the preparation of nifedipine amorphous solid dispersions (ASDs) was determined through the time-temperature-transformation (TTT) diagram. ASDs were prepared with polyvinylpyrrolidone, hydroxypropylmethyl cellulose acetate succinate, and poly(acrylic acid). ASDs were subjected to isothermal crystallization over a wide temperature range, and the time and temperature dependence of nifedipine crystallization onset time (tC) was determined by differential scanning calorimetry (DSC) and synchrotron X-ray diffractometry. TTT diagrams were generated for ASDs, which provided the CRcrit for the dispersions prepared with each polymer. The observed differences in CRcrit could be explained in terms of differences in the strength of interactions. Stronger drug-polymer interactions led to longer tC and decreased CRcrit. The effect of polymer concentrations (4-20% w/w) was also influenced by the strength of the interaction. The CRcrit of amorphous NIF was â¼17.5 °C/min. Addition of 20% w/w polymer resulted in a CRcrit of â¼0.05, 0.2, and 11 °C/min for the dispersions prepared with PVP, HPMCAS, and PAA, respectively.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Polímeros
/
Nifedipino
Idioma:
En
Revista:
Mol Pharm
Assunto da revista:
BIOLOGIA MOLECULAR
/
FARMACIA
/
FARMACOLOGIA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos