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

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 alpha-maltose and methanol as a representative sugar and organic solvent. The apparent molar volume of alpha-maltose was similar to 30% smaller in methanol than in water. The methanol-originated amorphous alpha-maltose exhibited a much greater degree of hydrogen bonding than the water-originated one. Considering these findings, we conclude that the alpha-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 alpha-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. (c) 2019 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.