Abstract
The potassium (K), sodium (NA), calcium (CA), and magnesium (MG) salts of p-aminosalicylic acid were obtained, and their thermal behavior was characterized by means of differential scanning calorimetry (DSC) and thermogravimetric analysis (TG). Their crystal and molecular structures were determined by single-crystal X-ray diffraction after powder patterns had shown them to be nonisomorphous. Different degrees of hydration were observed for the solid salts, and an assessment of hydrate stability to dehydration was made from thermogravimetric studies. The onset temperature of dehydration (T t) of each salt varied within the series and exhibited correlation with X-ray determined structure. The observed onset of dehydration of MG and CA was higher than that of NA and is consistent with stronger ion-dipole interactions for the divalent salts. Crystallographic determination of the bond lengths between the metal ion and the water oxygens were 2.4 and 2.9 Å for NA, between 2.0 and 2.1 Å for MG, and 2.4 Å for CA. The open nature and presence of a channel feature in the structure of the sodium salt may have facilitated escape of water molecules from the crystal. Particle presentation (e.g., size, crystallinity) was also shown to affect dehydration behavior.
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REFERENCES
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).
L. Gu, O. Huynh, A. Becker, S. Peters, H. Nguyen, and N. Chu. Preformulation selection of a proper salt for a weak acid-base (RS-82856)—a new positive inotropic agent. Drug Dev. Ind. Pharm. 13:437–448 (1987).
P. H. Jones, E. K. Rowley, A. L. Weiss, D. L. Bishop, and A. H. C. Chun. Insoluble erythromycin salts. J. Pharm. Sci. 58:337–339 (1969).
E. J. Benjamin and L. H. Lin. Preparation and in vitro evaluation of salts of an antihypertensive agent to obtain slow release. Drug Dev. Ind. Pharm. 11:771–790 (1985).
W. D. Walkling, B. E. Reynolds, B. J. Fegely, and C. A. Janicki. Xilobam: Effect of salt form on pharmaceutical properties. Drug Dev. Ind. Pharm. 9:809–819 (1983).
A. A. Kondritzer, R. I. Ellin, and L. J. Edberg. Mineral acid salts of lidocaine. J. Pharm. Sci. 50:109–112 (1961).
H. M. Koehler and J. J. Heffenen. Investigation of methyl pyridium-2-aldoxime salts. J. Pharm. Sci. 53:1126–1127 (1964).
S. M. Berge, L. D. Bighley, and D. C. Monkhouse. Pharmaceutical salts. J. Pharm. Sci. 66:1–19 (1977).
P. L. Gould. Salt selection for basic drugs. Int. J. Pharm. 33:201–217 (1986).
S. R. Byrn. Solid-State Chemistry of Drugs Academic Press, New York, 1982.
D. F. Adams. Inorganic Solids John Wiley and Sons, London, 1974.
C. T. Lin, P. Y. Siew, and S. R. Byrn. Solid-state dehydrochlorination and decarboxylation reactions. 1. Reactions of p-aminosalicylic acid hydrochloride and p-aminosalicylic acid, and revised crystal structure of p-aminosalicylic acid. J. Chem. Soc. Perkin Trans II:957–962 (1978).
C. T. Lin, P. Y. Siew, and S. R. Byrn. Solid-state dehydrochlorination and decarboxylation reactions. 2. Reactions of three crystal habits of p-aminosalicylic acid hydrochloride and the crystal structure of p-aminosalicylic acid hydrochloride. J. Chem. Soc. Perkin Trans II:963–968 (1978).
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Forbes, R.T., York, P., Fawcett, V. et al. Physicochemical Properties of Salts of p-Aminosalicylic Acid. I. Correlation of Crystal Structure and Hydrate Stability. Pharm Res 9, 1428–1435 (1992). https://doi.org/10.1023/A:1015806812349
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DOI: https://doi.org/10.1023/A:1015806812349