An approach to early-phase salt selection: Application to NBI-75043

Organic Process Research and Development

Volumn 11, Issue 3, 2007, Pages 365-377

  Gross, Timothy D ^a   Schaab, Kevin ^a   Ouellette, Michael ^a   Zook, Scott ^a   Reddy, Jayachandra P ^a   Shurtleff, Arthur ^a   Sacaan, Aida I ^a   Alebic Kolbah, Tanja ^a   Bozigian, Haig ^a  

^a NEUROCRINE BIOSCIENCES INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 39049163486     PISSN: 10836160     EISSN: None     Source Type: Journal    
DOI: 10.1021/op060221a     Document Type: Article

References (26)

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5. (a) Kaneko, Y.; Shimada, K.; Saitou, K.; Sugimoto, Y.; Kamei, C. Methods Find. Exp. Clin. Pharmacol. 2000, 22, 163-168.
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7. (c) Timmerman, H. In Therapeutic Index of Antihistamines; Church, M. K., Rihoux, J.-P., Eds.; Bern, Hogrefe & Huber: New York, Toronto, 1992; pp 19-31.
8. Details of route development and scale-up work will be the subject of a future paper.
9. (a) Gould, P. L. Int. J. Pharm. 1986, 33, 201-217.
10. (b) Berge, S. M.; Bighley, L. D.; Monkhouse, D. C. J. Pharm. Sci. 1977, 66 (1), 1-19.
11. (c) Maurin, M. B.; Rowe, S. M.; Koval, C. A.; Hussain, M. A. J. Pharm. Sci. 1994, 83 (10), 1418-1420.
12. (d) Bastin, R. J.; Bowker, M. J.; Slater, B. Org. Proc. Res. Dev. 2000, 4, 427-435.
13. (e) Handbook of Pharmaceutical Salts Properties, Selection, and Use; Stahl, P. H., Wermuth, C. G., Eds.; Wiley-VCH: Weinheim, 2002.
14. To form a stable salt, it is recommended to have 3 pK units difference between the base and counterion (see ref 5d).
15. Caution should be exercised when selecting maleic or fumaric acid as these acids are known to form covalent adducts with amines. See Anderson, N. G. Practical Process Research & Development; Academic Press: San Diego; 2000; pp 239-240.
16. Chen, C.-K.; Singh, A. K. Org. Process Res. Dev. 2001, 5, 509.
17. (a) Physical Characterization of Pharmaceutical Solids; Brittain, H. G., Ed.; Drugs and the Pharmaceutical Sciences, Vol. 70; New York: Marcel Dekker, 1995; pp 14-18.
18. (b) Polymorphism in Pharmaceutical Solids; Brittain, H. G., Ed.; Drugs and the Pharmaceutical Sciences, Vol. 95; New York: Marcel Dekker, 1999; pp 251-256.
19. Rankell, A.; Lieberman, H. A. In The Theory and Practice of Industrial Pharmacy; Lachman, L., Lieberman, H. A., Kanig, J. L., Eds.; Lea & Febiger: Philadelphia, 1970; pp 62-67.
20. Purity values reported exclude any contributions from the acids (if any) at 260 nm.
21. There were small differences in th PXRD data presented in Figure 3: the peak at ∼ 14.5 2θ is diminished in the ethyl acetate sample an the peak at ∼ 41 2θ is increased in the acetonitrile sample. These changes are most likely due to particle size or orientation and do not suggest different polymorphs. Subtle shifts on the PXRD for different polymorphs may lead to processing challenges. See Remenar, J. F.; MacPhee, J. M.; Larson, B.; Almarsson, O. Org. Process Res. Dev. 2003, 7, 990. It is particularly useful to employ orthogonal methods of characterization when undertaking studies of polymorphism in pharmaceutical solids (see ref 9a). In addition to powder and single-crystal X-ray diffraction techniques, DSC, FTIR spectroscopy (see: Roy, S.; Atipamula, S.; Nangia, A. Cryst. Growth Des. 2005, 5, 2268-2276; Park, K.; Evans, J. M. B.; Myerson, A. S. Cryst. Growth Des. 2003, 3, 991-995), Raman spectroscopy (see: Wang, F.; Wachter, J. A.; Antosz, F J.; Berglund, K. A. Org. Process Res. Dev. 2000, 4, 291-295), optical microscopy (see: Cashell, C.; Sutton, D.; Corcoran, D.; Hodnett, B. K. Cryst. Growth Des. 2003, 3, 869-872; Wahlstrom, E. E. Optical Crystallography, 5th ed.; J. Wiley and Sons: New York, 1979), and crystal modeling (see: Arslantas, A.; Ermler, W. C.; Yazici, R.; Kalyon, D. M. Int. J. Mol. Sci. 2005, 6, 291-302) are conventional techniques employed in characterizing polymorphism in pharmaceutical solids. Additional general texts for the characterization of pharmaceutical solids include (a) Byrn, S. R. Solid-State Chemistry of Drugs; Academic Press: New York, 1982.
22. (b) Allen, L. V.; Popovich, N. G.; Ansel, H. C. Ansel's Pharmaceutical Dosage Forms and Drug Delivery Systems, 8th ed.; Lippincott Williams and Wilkins: Baltimore, MD, 2005.
23. Guidance fo Industry Q3C - Tables and Lists; U.S. Department of Health and Human Services Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER), ICH, revision 1: Washington, D.C., November, 2003.
24. The feasibility of thermal conversion was under investigation. Chloroform, a class 2 solvent was selected as it possesses vastly different properties than the esters. Had thermal conversion been successful, a search for alternate solvents would have been performed.
25. A similar conversion of an API salt to a more stable form by controlling water to >0.2% has been reported by Grosso, J. A. U.S. Patent 5,162,543, 1992. Ethanol/water, 95:5, is the solvent most often used for salt formation when performing optical resolutions (Jaques, J.; Collet, A.; Wilen, S. H. Enantiomers, Racemates and Resolutions; Wiley: New York, 1981; pp 381-395). Its inclusion in a solvent screen may be helpful in identifying hydrated forms.
26. McCrone, W. C. Physics and Chemistry of the Organic Solid State; Wiley-Interscience Publishers: New York, 1965; pp 725-767.