Quantitative Analysis of Drug Supersaturation Region by Temperature-Variable Nuclear Magnetic Resonance Measurements, Part 1: Effects of Polymer and Drug Chiralities.
Mol Pharm
; 20(4): 1861-1871, 2023 04 03.
Article
en En
| MEDLINE
| ID: mdl-36939575
We examined the effects of the polymer-additive and drug chiralities on the ketoprofen (KTP) supersaturation region using temperature-variable nuclear magnetic resonance (NMR). Quantitative NMR analysis revealed that the racemic KTP and corresponding S-enantiomer (rac- and s-KTP) exhibited similar amorphous solubilities in a buffer, while the crystalline solubility of s-KTP was higher than that of rac-KTP. Therefore, rac-KTP exhibited a larger supersaturation region than s-KTP. In contrast, polyvinylpyrrolidone (PVP) reduced the amorphous solubility of both rac- and s-KTP, whereas the crystalline solubility of KTP remained unchanged. Partitioning PVP into the KTP-rich phase reduced the chemical potential of KTP in the KTP-rich phase and the amorphous solubility of KTP. At higher temperatures, the distribution of PVP into the KTP-rich phase became more significant, which considerably reduced the amorphous solubility. Because the upper limit of the KTP supersaturation decreased, PVP narrowed the KTP supersaturation region. The maximum KTP supersaturation ratio decreased with increasing temperature, and the supersaturated dissolvable area of KTP finally disappeared. The maximum temperature at which KTP can form the supersaturation was lowered by replacing rac- with s-KTP and the addition of PVP. The maximum supersaturation temperature was dominated by the melting behavior of crystalline KTP in an aqueous solution. The present study highlighted that a quantitative understanding of the supersaturation region is essential to determine whether supersaturated formulations are beneficial for improving the oral absorption of poorly water-soluble drugs.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Polímeros
/
Cetoprofeno
Idioma:
En
Revista:
Mol Pharm
Asunto de la revista:
BIOLOGIA MOLECULAR
/
FARMACIA
/
FARMACOLOGIA
Año:
2023
Tipo del documento:
Article
País de afiliación:
Japón
Pais de publicación:
Estados Unidos