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|Title:||Effect of water activity on the transformation between hydrate and anhydrate of carbamazepine|
|Citation:||Li, Y., Chow, P.S., Tan, R.B.H., Black, S.N. (2008-03). Effect of water activity on the transformation between hydrate and anhydrate of carbamazepine. Organic Process Research and Development 12 (2) : 264-270. ScholarBank@NUS Repository. https://doi.org/10.1021/op7001497|
|Abstract:||Pharmaceutical hydrates have substantial impact on the bioavailability of drugs, and controlling the formation of hydrates is of significant importance in the pharmaceutical crystallization and formulation processes. The relative stability of carbamazepine anhydrate (CBZA) and dihydrate(CBZD) at room temperature was investigated by using slurry experiments. Optical microscopy, powder X-ray diffraction, Karl Fischer titration, thermogravimetric analysis, and differential scanning calorimetry were used to characterize CBZA and CBZD. The results of slurry experiments showed that the water content at equilibrium plays a vital role in determining the relative stability of CBZA and CBZD. At 20°C, CBZD is more stable than CBZA when the water content of the solvent mixture in equilibrium (Cwe) is higher than 19.6%, and vice versa. It was also found that CBZD and CBZA can coexist in equilibrium when C we is equal to 19.6% or water activity of 0.636 at 20°C. The three-component phase diagram was established for better understanding of the relationship between the water content and the relative stability of CBZD and CBZA. The compositions at which CBZD and CBZA can coexist at high CBZ content can be displayed usefully by the three-component phase diagram. This demonstrates the importance of three-component phase diagrams for analyzing the relative stability of pharmaceutical anhydrates and hydrates. © 2008 American Chemical Society.|
|Source Title:||Organic Process Research and Development|
|Appears in Collections:||Staff Publications|
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