Titre du document / Document title

Phase behavior of amorphous molecular dispersions II: Role of hydrogen bonding in solid solubility and phase separation kinetics

Auteur(s) / Author(s)

VASANTHAVADA Madhav ; TONG Wei-Qin ; JOSHI Yatindra ; SERPIL KISLALIOGLU M. ;

Résumé / Abstract

Purpose. To determine the factors influencing "solid solubility" and phase separation kinetics of drugs from amorphous solid dispersions. Methods. Solid dispersions of griseofulvin-poly(vinyl pyrrolidone) (PVP) and indoprofen-PVP were prepared using solvent evaporation technique. Dispersions demonstrating single T^g were exposed to 40°C/69% RH for 90 days. Drug solid solubility in the polymer and phase separation rates were determined from changes in T^g of solid dispersions. FTIR spectroscopy and XRD were used to characterize drug-polymer interactions and drug crystallinity, respectively. Results. Freshly prepared solid dispersion of up to 30% w/w griseofulvin and indoprofen were molecularly miscible with PVP. Hydrogen bonding was evident in indoprofen-PVP, but not in griseofulvin-PVP dispersions. When exposed to 40°C/69% RH, griseofulvin phase separated completely, whereas the solid solubility of indoprofen was determined as 13% w/w. The first-order rate constants of phase separation for 10%. 20%, and 30% w/w griseofulvin dispersions were estimated as 4.66, 5.19, and 12.50 (×10₂) [day_-1], and those of 20% and 30% w/w indoprofen dispersions were 0.62 and 1.25 (×10₂) [day_-1], respectively. Conclusions. Solid solubility of griseofulvin and indoprofen in PVP is -0% w/w and -13% w/w, respectively. Drug-polymer hydrogen bonding in indoprofen-PVP dispersions favors solid solubility. Phase separation rate of drug from the solid dispersions depends on the initial drug content and the nature of drug-polymer interactions.

Revue / Journal Title

Pharmaceutical research   ISSN 0724-8741   CODEN PHREEB 

Source / Source

2005, vol. 22, n^o3, pp. 440-448 [9 page(s) (article)]

Langue / Language

Anglais

Editeur / Publisher

Springer, New York, NY, ETATS-UNIS  (1984) (Revue)

Localisation / Location

INIST-CNRS, Cote INIST : 20257, 35400012953064.0130