Abstract |
Creatine phosphate sodium (CPS) salt is a first-line cardiovascular drug for severe diastolic heart failure. The drug exists in different hydrate forms. The marketed drug form was determined as CPS·4.5H2 O (H1); however, the reference standard was supplied as CPS·6H2 O (H2). In this work, we present two newly identified hydrate forms: a thermodynamically stable low hydrate form, CPS·1.5H2 O (H3), and a pressure-sensitive transit form, CPS·7H2 O (H4). The hydrate forms were discovered through a comprehensive solid-state screening experiment and fully characterized using a range of analytical techniques including X-ray powder diffraction (XRPD), FTIR, Raman spectroscopy, hot-stage microscopy (HSM), thermogravimetric analysis, and differential scanning calorimetry. Stability tests revealed that H3 was the most stable hydrate under thermal stimulation. H4 is a pressure-sensitive hydrate and easily transforms to H2 and then H1 upon grinding. The form transformation process was closely monitored using the HSM, variable-temperature XRPD (VT-XRPD), and VT-Raman spectroscopy techniques. Specifically, the transformation of H4 to H1 is characterized in a single-crystal-to-single-crystal transformation process. The newly discovered hydrate form H3 has superior physicochemical properties than the marketed forms and is worthy of further development.
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Authors | Yun Xu, Linglei Jiang, Ying Huang, Jian-Rong Wang, Xuefeng Mei |
Journal | Journal of pharmaceutical sciences
(J Pharm Sci)
Vol. 103
Issue 11
Pg. 3688-3695
(Nov 2014)
ISSN: 1520-6017 [Electronic] United States |
PMID | 25223726
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association. |
Chemical References |
- Cardiotonic Agents
- Phosphocreatine
- Water
|
Topics |
- Calorimetry, Differential Scanning
- Cardiotonic Agents
(chemistry, standards)
- Chemistry, Pharmaceutical
- Crystallization
- Crystallography, X-Ray
- Drug Packaging
- Drug Stability
- Drug Storage
- Microscopy, Polarization
- Molecular Structure
- Phosphocreatine
(chemistry, standards)
- Powder Diffraction
- Pressure
- Quality Control
- Spectroscopy, Fourier Transform Infrared
- Spectrum Analysis, Raman
- Technology, Pharmaceutical
(methods)
- Temperature
- Thermogravimetry
- Water
(chemistry)
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