کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2486759 | 1114392 | 2010 | 9 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Transformation Pathways of Cocrystal Hydrates When Coformer Modulates Water Activity Transformation Pathways of Cocrystal Hydrates When Coformer Modulates Water Activity](/preview/png/2486759.png)
ABSTRACTAn important attribute of cocrystals is that their properties can be tailored to meet required solubility and stability specifications. But before such practical uses can be realized, a better understanding of the factors that dictate cocrystal behavior is needed. This study attempts to explain the phase behavior of anhydrous/hydrated cocrystals when the coformer modulates both water activity and cocrystal solubility. Stability dependence on solution composition and water activity was studied for theophylline-citric acid (THP–CTA) anhydrous and hydrated cocrystals by both suspension and vapor equilibration methods. Eutectic points and associated water activities were measured by suspension equilibration methods to determine stability regions and phase diagrams. The critical water activity for the anhydrous-hydrate cocrystal was found to be 0.8. It is shown that (a) both water and coformer activities determine phase stability, and (b) excipients that alter water activity can profoundly affect the hydrate/ anhydrous eutectic points and phase stability. Vapor phase stability studies demonstrate that cocrystals of highly water soluble coformers, such as citric acid, are predisposed to conversions due to moisture uptake and deliquescence of the coformer. The presence of such coformers as trace level impurities with cocrystal will alter hygroscopic behavior and stability.
Journal: Journal of Pharmaceutical Sciences - Volume 99, Issue 9, September 2010, Pages 3977–3985