Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10162462 | Journal of Pharmaceutical Sciences | 2014 | 8 Pages |
Abstract
The relationship between the miscibility of formulation ingredients and their crystallization during the freezing segment of the lyophilization process was studied. The thermal properties of frozen solutions containing myo-inositol and cosolutes were obtained by performing heating scans from â70°C before and after heat treatment at â20°C to â5°C. Addition of dextran 40,000 reduced and prevented crystallization of myo-inositol. In the first scan, some frozen solutions containing an inositol-rich mixture with dextran showed single broad transitions (Tgâ²s: transition temperatures of maximally freeze-concentrated solutes) that indicated incomplete mixing of the concentrated amorphous solutes. Heat treatment of these frozen solutions induced separation of the solutes into inositol-dominant and solute mixture phases (Tgâ² splitting) following crystallization of myo-inositol (Tgâ² shifting). The crystal growth involved myo-inositol molecules in the solute mixture phase. The amorphous-amorphous phase separation and resulting loss of the heteromolecular interaction in the freeze-concentrated inositol-dominant phase should allow ordered assembly of the solute molecules required for nucleation. Some dextran-rich and intermediate concentration ratio frozen solutions retained single Tgâ²s of the amorphous solute mixture, both before and after heat treatments. The relevance of solute miscibility on the crystallization of myo-inositol was also indicated in the systems containing glucose or recombinant human albumin.
Keywords
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Authors
Ken-Ichi Izutsu, Hiroko Shibata, Hiroyuki Yoshida, Yukihiro Goda,