Abstract
Purpose. This review describes a conceptual approach to the characterization of pharmaceutical solids.
Methods. Four flow charts are presented: (1) polymorphs, (2) hydrates, (3) desolvated solvates, and (4) amorphous forms.
Results. These flow charts (decision trees) are suggested as tools to develop information on pharmaceutical solids for both scientific and regulatory purposes.
Conclusions. It is hoped that this review will lead to a more direct approach to the characterization of pharmaceutical solids and ultimately to faster approval of regulatory documents containing information on pharmaceutical solids.
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REFERENCES
A. Miyamae, S. Koda, S. Kitamura, Y. Okamoto, and Y. Morimoto. X-ray crystallographic characterization of two polymorphs of 8-(2-methoxycarbonylamino-6-methylbenzyloxy)-2-methyl-3-(2-propynyl)imidazo[1,2-a]pyridine, J. Pharm. Sci. 79: 189–195 (1990).
P. A. Saindon, N. S. Cauchon, P. A. Sutton, C. J. Chang, G. Peck, and S. R. Byrn. Solid-state nuclear magnetic resonsance (NMR) spectra of pharmaceutical dosage forms, Pharm. Res. 10: 197–203 (1993).
D. E. Bugay. Solid-state nuclear magnetic resonance spectroscopy: Theory and pharmaceutical applications, Pharm. Res. 10: 317–327.
J. K. Haleblian and W. C. McCrone. Pharmaceutical Applications of Polymorphism, J. Pharm. Sci. 58: 911 (1969).
W. I. Higuchi, P. K. Lau, T. Higuchi, and J. W. Shell. Polymorphism and Drug Availability, J. Pharm. Sci. 52: 150–153 (1963).
D. P. Ip, G. S. Brenner, J. M. Stevenson, S. Lindenbaum, A. W. Douglas, S. D. Klein, and J. A. McCauley. High resolution spectroscopic evidence and solution calorimetry studies on the polymorphs of enalapril maleate, Int. J. Pharm. 28: 183–191 (1986).
Y. Matsuda, E. Tatsumi, E. Chiba, and Y. Miwa. Kinetic study of the polymorphic transformations of phenylbutazone, J. Pharm. Sci. 73: 1453–1460 (1984).
V. P. Tanninen and J. Yliruusi. X-ray powder diffraction profile fitting in quantitative determination of two polymorphs from their powder mixture, Int. J. Pharm. 81: 169–177 (1992).
G. A. Stephenson, J. G. Stowell, P. H. Toma, D. E. Dorman, J. R. Greene, and S. R. Byrn. Solid-State Analysis of Polymorphic, Isomorphic, and Solvated Forms of Dirithromycin, J. Am. Chem. Soc. 116: 5766–5773 (1994).
C. A. Hirsch, R. J. Messenger, and J. L. Brannon. Fenoprofen: drug form selection and preformulation stability studies, J. Pharm. Sci. 67: 231–236 (1978).
S. Niazi. Thermodynamics of mercaptopurine dehydration, J. Pharm. Sci. 67: 488–491 (1978).
T. Ishida, M. Doi, M. Shimamoto, N. Minamino, K. Nonaka, and M. Inoue. Physicochemical properties of crystalline forms of ethynylestradiol solvates: comparison of thermal behavior with x-ray crystal structure, J. Pharm. Sci. 78: 274 (1989).
G. Zografi, D. Hollenbeck, S. Laughlin, M. Pikal, J. Schwartz, and L. VanCampen. Report of the advisory panel on moisture specifications, Pharmacopeial Forum: 1459–1474 (1991).
C. T. Lin, P. Perrier, G. G. Clay, P. A. Sutton, and S. R. Byrn. Solid-State Photooxidation of Cortisol-21-tert-butylacetate to Cortisone-21-tert-butylacetate, J. Org. Chem. 47: 2978–82 (1982).
S. R. Byrn, P. A. Sutton, B. Tobias, J. Frye, and P. Main. Crystal structure, solid-state NMR spectra, and oxygen reactivity of five crystal forms of prednisolone tert-butylacetate, J. Am. Chem. Soc. 110: 1609–1614 (1988).
Y. Matsuda and E. Tatsumi. Physicochemical characterization of furosemide modifications, Intl. J. Pharm. 60: 11–26 (1990).
C. Doherty and P. York. Furosemide crystal forms; solid state and physicochemical analyses, Int. J. Pharm. 47: 141–155 (1988).
E. Shefter and T. Higuchi. Dissolution behavior of crystalline solvated and nonsolvated forms of some pharmaceuticals, J. Pharm. Sci. 52: 781–791 (1963).
I. Himuro, Y. Tsuda, K. Sekiguchi, I. Horikoshi, and M. Kanke. Studies on the method of size reduction of medicinal compounds. IV. Solvate formation of chloramphenicol and its application to size reduction, Chem. Pharm. Bull. 19: 1034–1040 (1971).
M. J. Pikal, A. L. Lukes, J. E. Lang, and K. Gaines. Quantitative crystallinity determinations for beta-lactam antibiotics by solution calorimetry: correlations with stability, J. Pharm. Sci. 67: 767–769 (1978).
E. Fukuoka, M. Makita, and S. Yamamura. Some physicochemical properties of glassy indomethacin, Chem. Pharm. Bull. 34: 4314–4321 (1986).
E. Fukuoka, M. Makita, and S. Yamamura. Glassy state of pharmaceuticals III. Thermal properties and stability of glassy pharmaceuticals and their binary glass systems, Chem. Pharm. Bull. 37: 1047–1050 (1989).
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Byrn, S., Pfeiffer, R., Ganey, M. et al. Pharmaceutical Solids: A Strategic Approach to Regulatory Considerations. Pharm Res 12, 945–954 (1995). https://doi.org/10.1023/A:1016241927429
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DOI: https://doi.org/10.1023/A:1016241927429