Influence of Glass Forming Ability on the Physical Stability of Supersaturated Amorphous Solid Dispersions

Lasse Ingerslev Blaabjerg, Bulut Bulduk, Eleanor Lindenberg, Korbinian Löbmann*, Thomas Rades, Holger Grohganz

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

36 Citations (Scopus)

Abstract

In this study, the influence of the glass-forming ability (GFA) of a drug on its physical stability in a supersaturated solid dispersion was investigated. Nine drugs were classified according to their GFA using their respective critical cooling rate. Their respective solubility in poly(vinylpyrrolidone-co-vinyl acetate) 6:4 (PVPVA64) was predicted using the melting point depression method based on the Flory-Huggins lattice theory. Supersaturated amorphous solid dispersions at a level of 25% w/w drug above saturation solubility in the polymer were prepared by film-casting, and their respective physical stability at temperatures of 10°C or 20°C above or below their respective T g (dry conditions) was monitored by the use of polarized light microscopy. This study showed that drugs with good GFA (class 3) on average have higher physical stability in supersaturated amorphous solid dispersion compared to drug with modest GFA (class 2), which in turn have higher physical stability in supersaturated amorphous solid dispersion than drugs with poor GFA (class 1). These results indicate that the GFA of a drug and its physical stability in a supersaturated amorphous solid dispersion stored at a temperature above or below its T g are correlated.

Original languageEnglish
JournalJournal of Pharmaceutical Sciences
Volume108
Issue number8
Pages (from-to)2561-2569
ISSN0022-3549
DOIs
Publication statusPublished - 1 Jan 2019

Keywords

  • amorphous
  • crystallization
  • formulation
  • glass
  • physical stability
  • solid dispersion
  • solid state
  • solubility

Cite this