Estimating the relative stability of polymorphs and hydrates from heats of solution and solubility data

✍ Scribed by Chong-Hui Gu; David J. W. Grant

• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: English
• Weight: 183 KB
• Volume: 90
• Category: Article
• ISSN: 0022-3549
• DOI: 10.1002/jps.1080

✦ Synopsis

The transition temperature, T t , of polymorphs is estimated from both their heats of solution and solubilities (or intrinsic dissolution rates) determined at any one temperature (e.g., ambient). At a given temperature, T, the enthalpy difference, DH, between polymorphs, I and II, is equal to the difference between their heats of solution, whereas the free energy difference, DG, can be estimated by the equation, DG ÀRTln (c I /c II ) or DG ÀRTln (J I /J II ), where c is the solubility and J is the intrinsic dissolution rate. The entropy difference, DS, is evaluated as (DH À DG)/T. Because the heat capacity difference, DC p between polymorphs is small enough to be neglected, the transition temperature may be estimated by the equation, T t DH/DS. The thermodynamic stability relationships of the polymorphs (i.e., whether they are enantiotropes or monotropes) are predicted from the value of T t and the melting temperature. The T t values for aurano®n, carbamazepine, chloramphenicol palmitate, cyclopenthiazide, gepirone hydrochloride, lamivudine, MK571, prema¯oxacin, sulfamerazine, sulfamethoxazole, sulfathiazole, and urapidil, were calculated from reported values of the heats of solution and solubilities (or dissolution rates). The stability relationships deduced from the calculated values of T t are in good agreement with those reported using other methods, such as differential scanning calorimetry and interpretation of melting data.