Figure 12
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The crystal habit and aspect ratio of length-to-breath of (R, S)-(±)-sodium ibuprofen dihydrate crystals produced from the nine pure solvents are shown in Figure 11. Most of the crystals
grown from THF, n-butyl alcohol, IPA, benzyl alcohol, ethanol, methanol, and water were hexagonal plates. There was a strong correlation between
high values of the polar component (δp) and the aspect ratio of crystals. For polar aprotic good solvents such as DMF and DMSO, high δp might have induced the rapid growth of polar (001) faces containing sodium ions and carboxylic groups (12, 26) in the [010]
direction to form long needles rather than two-dimensional plates as verified by the SEM micrograph showing the (001) faces
without the sandwiched layers as the major (010) planes (see Figures 10 and 12). The hexagonal plate and rod-like crystal
habits grown from the nine pure solvents were all plotted against the Hansen parameters in Figure 13. To test the predictability
of the 3-D Hansen plot (see Figure 13), (R, S)-(±)-sodium ibuprofen dihydrate was grown in another polar aprotic solvent, acetonitrile with a high δp of 18 MPa1/2. Needle-shape crystals were produced as expected (see Figure 14).
Conclusion
Figure 13
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Useful scale-up and drug development data of solubility, polymorphism, crystallinity, crystal habit, and drying schemes of
(R, S)-(±)-sodium ibuprofen dihydrate crystals were generated by the initial solvent-screening method. Solubility data were processed
and treated with the van't Hoff equation, form space, and solubility sphere. The dependency of crystal habits on solvents
and drying schemes were derived using optical microscopy and scanning electron microscopy. The relationships between crystal
habits and microscopic properties of solvents were plotted by a 3-D Hansen model. In principle, the initial solvent-screening
strategy can be readily extended to and integrated with food, explosives, optoelectronics, agricultural, and ceramics products.
Acknowledgment
Figure 14
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This work was supported by a grant from the National Science Council of Taiwan, Republic of China (NSC 95-2113-M-008-012-MY2).
Assistance from Ling-I Hung, PhD, postdoctoral, at the Solid-State Inorganic Chemistry Laboratory on Diamond 3.1 computer
software, suggestions from Jui-Mei Huang in differential scanning calorimetry and thermal gravimetric analysis, and Shew-Jen
Weng in X-ray diffraction, all with the Precision Instrument Center at the National Central University gratefully are acknowledged.
Tu Lee,* PhD, is an assistant professor at the Department of Chemical and Materials Engineering and the Institute of Materials Science
and Engineering, National Central University, 300 Jhong-Da Rd, Jhong-Li City 320, Taiwan, Republic of China tel. + 886-3-422-7151, ext. 34204, fax + 886-3-425-2296, tulee@cc.ncu.edu.tw
Ying Hsiu Chen and Chyong Wen Zhang are graduate students, the Department of Chemical and Materials Engineering, National Central University.
*To whom all correspondence should be addressed.
Submitted: Dec. 11, 2006. Accepted:Jan. 24, 2007.
Key words: form space, Hansen model, racemic (R,S)-(±) sodium ibuprofen dihydrate, solubility sphere
References
1. B. J. Armitage, J. F. Lampard, and A. Smith, "Composition of S-Sodium Ibuprofen," US Patent 6,242,000 B1 (2001).
2. A. Gracin and A.C. Rasmuson, "Solubility of Phenylacetic Acid, P-hydroxyphenylacetic Acid, P-aminophenylacetic acid, P-hydroxybenzoic acid, and Ibuprofen in Pure Solvents," J. Chem. Eng. Data 47 (6), 1379–1383 (2002).
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