Other approaches
Researchers at the University of Missouri recently reported on a new method for converting drugs from one crystalline form
to another by applying gas-induced transformations of the antibiotic clarithromycin and lansoprazole, the API in the gastrointestinal
drug Prevacid.
For clarithromycin, the researchers converted the kinetic solvent and guest-free crystal forms to the commercially thermodynamically
stable polymorph with a reduction in energy costs relative to other commonly used methods. Typical methods involve desolvation
of the initial form to a second form, which is heated for 18 h at 110 °C to finally produce the desired polymorph. In the
gas-induced process, the clarithromycin crystals were pressurized with carbon dioxide at 350 psi for direct conversion of
the initial form to the final thermodynamically stable form in 4 h. For lansoprazole, the researchers also used carbon dioxide
to convert the ethanol hydrate of lansoprazole to the solvent-free form that is used commercially. This process improved the
approach used in synthesizing lansoprazole, which involves a solvate that readily decomposes and is stirred in water, filtered,
and dried intensively (8, 9).
Patricia Van Arnum is a senior editor at Pharmaceutical Technology, 485 Route One South, Bldg F, First Floor, Iselin, NJ 08830 tel. 732.346.3072, pvanarnum@advanstar.com
.
References
1. S.J. Byard et al., J. Pharm. Sci. 94 (6), 1321– 1335 (2005).
2. T.N. Pham et al., Mol. Pharm. 7 (5), 1667–1691 (2010).
3. NMR Crysallography, R. Harris, R.E. Wasylisher, and M.J. Duer, Eds. (John Wiley & Sons, Chichester, UK, 2009).
4. S.M. Reutzell-Edens, "NMR Crystallography and the Elucidation of Structure–Property Relationships in Crystalline Solids,"
in Engineering of Crystalline Materials Properties, NATO Science for Peace and Security Series B: Physics and Biophysics, J. Novoa, D. Braga, and L. Addadi Eds (Springer, Dordrecht, The Netherlands, 2008), pp. 351–374.
5. J.S. Stevens, S.J. Byard, and S.L.M. Schroeder, J. Pharm. Sci.
99 (11), 4453–4457 (2010).
6. J. S. Stevens et al., J. Phys. Chem. B. 114 (44) 13961–13969 (2010).
7. J.S. Stevens et al., J. Pharm. Sci.
100 (3) 942– 948 (2011).
8. J. Tian, S.J. Dalgarno, and J.L. Atwood, J. Am. Chem. Soc.
133 (5), 1399–1404 (2011).
9. C. Arnaud, Chem. & Eng News
89 (3), 8 (2011).
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