Physical Stability of an Amorphous Sugar Matrix Dried From Methanol as an Amorphous Solid Dispersion Carrier and the Influence of Heat Treatment

Koji Takeda, Takanari Sekitoh, Akiho Fujioka, Kayoko Yamamoto, Takashi Okamoto, Tsutashi Matsuura, Hiroyuki Imanaka, Naoyuki Ishida, Koreyoshi Imamura

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

An amorphous sugar matrix, after drying from an organic solvent, was investigated for use as a method for dispersing hydrophobic drugs (solid dispersion). However, the amorphous sugar, originally contained in the organic solvent, had a significantly low glass transition temperature (T g ), thus rendering it physically unstable. In this study, we examined the physicochemical properties of a sugar in a dried matrix and in an organic solvent, using α-maltose and methanol as a representative sugar and organic solvent. The apparent molar volume of α-maltose was ∼30% smaller in methanol than in water. The methanol-originated amorphous α-maltose exhibited a much greater degree of hydrogen bonding than the water-originated one. Considering these findings, we conclude that the α-maltose maintained its compact conformation in the dried state and consequently caused the markedly low T g . Second, it was found that heating under appropriate conditions resulted in an increase in the T g of the methanol-originated amorphous α-maltose as well as a decrease in the level of hydrogen bonding. The aqueous dissolution of 2 model hydrophobic drugs (indomethacin and ibuprofen) from the solid dispersion was also improved as the result of the heat treatment, whereas, to the contrary, the dissolution of another model drug (curcumin) was lowered.

Original languageEnglish
JournalJournal of Pharmaceutical Sciences
DOIs
Publication statusPublished - Jan 1 2019

Keywords

  • amorphous solid dispersion
  • glass transition temperature
  • heat treatment
  • hydrophobic drug

ASJC Scopus subject areas

  • Pharmaceutical Science

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