Formation of Composite Crystals by Precipitation in Supercritical CO2

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• 作者：Boris Y. Shekunov ; Simon Bristow ; Albert H. L. Chow ; Lachlan Cranswick ; David J. W. Grant ; and Peter York
• 刊名：Crystal Growth & Design
• 出版年：2003
• 出版时间：July 2003
• 年：2003
• 卷：3
• 期：4
• 页码：603 - 610
• 全文大小：230K
• 年卷期：v.3,no.4(July 2003)
• ISSN：1528-7505

文摘

Acetaminophen (A) and p-acetoxyacetanilide (PAA) were used as model drug substances to studypurification and coformulation of structurally similar molecules by crystallization from supercritical CO₂. Incorporation of PAA into the crystal structure of A was defined by the mutual solubility of crystals of both molecules accordingto their different solvent-solute interactions, by the thermodynamics of the A-PAA solid solution phase, and by thekinetics of crystallization reflected by the specific surface interactions. The interaction between PAA and A resultedin significant changes to the crystal bulk and surface free energy, particle size, and morphology. Accuratedetermination of the lattice constants revealed the formation of a secondary A-PAA phase with a deformed crystallattice. The observed changes in the thermal behavior of the resulting solid solutions are explained mainly by changesof the entropy of the solid phase with smaller changes in enthalpy and even smaller elastic energy contributions.