| 1. |
- Nordström, Fredrik, et al.
(författare)
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Analysis of solution nonideality of a pseudomorphic drug system through a comprehensive thermodynamic framework for the design of a crystallization process
- 2004
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Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549 .- 1520-6017. ; 93:4, s. 995-1004
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Tidskriftsartikel (refereegranskat)abstract
- Solutions of a semipolar drug belonging to the alpha(v) beta(iii) integrin antagonist class of compounds were studied in a comprehensive thermodynamic framework. The solubility of two pseudomorphic forms (an anhydrate and a monohydrate) was measured at several temperatures and various solvent mixtures of acetonitrile and water. Both forms displayed a bell-shaped solubility behavior as a function of cosolvent composition. Thermodynamic framework used to analyze the data comprised van't Hoff and enthalpy-entropy compensation analyses. The two pseudomorphs exhibited linear temperature dependence from 25 to 65degreesC at all solvent compositions (i.e., ideal behavior with temperature for fixed solvent composition). Plots of enthalpy of solublization and Gibbs free energy showed two distinct regions with contrasting thermodynamic, and consequently, underlying structural properties (indicating non-deal behavior with solvent composition for a fixed temperature). Solubility increased due to entropy effects in the acetonitrile rich region, whereas enthalpy effects dominated solublization in the water-rich region. Quantification of this phenomenon by plotting DeltaH versus DeltaG showed considerable nonlinearity, and that the two regions were separated by a significant discontinuity-a trend rarely seen before in the literature. The reason behind this behavior is believed to be due to the complex interactions in the solution of the drug in water acetonitrile solvent system. A very significant aspect of the comprehensive thermodynamic analysis is that it helped explain the puzzling feature of the data, which showed that the free energy of phase transformation between the two pseudomorphic forms for a given temperature was not independent of the solvent composition. The resulting explanation has major consequences for crystallization process development.
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| 2. |
- Sheikh, J. A., et al.
(författare)
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Isovector and isoscalar superfluid phases in rotating nuclei
- 2000
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 6205:5
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Tidskriftsartikel (refereegranskat)abstract
- The subtle interplay between the two nuclear superfluids, isovector T=1, and isoscalar T=0 phases are investigated in an exactly soluble model. It is shown that T=1 and T=0 pair modes decouple in the exact calculations with the T=1 pair energy being independent of the T=0 pair strength and vice verse. In the rotating field, the isoscalar correlations remain constant in contrast to the well-known quenching of isovector pairing. An increase of the isoscalar (J=1,T=0) pair field results in a delay of the hand crossing frequency. This behavior is shown to be present only near the N=Z line and its experimental confirmation would imply a strong signature for isoscalar pairing collectivity. The solutions of the exact model are also discussed in the Hartree-Fock-Bogoliubov approximation.
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