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

The transition temperature, Tt, 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, ΔH, between polymorphs, I and II, is equal to the diff...

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Bibliographic Details
Published in:Journal of pharmaceutical sciences 2001-09, Vol.90 (9), p.1277-1287
Main Authors: Gu, Chong‐Hui, Grant, David J.W.
Format: Article
Language:English
Subjects:
Anti-Infective Agents - chemistry
Antibacterial agents
Antibiotics. Antiinfectious agents. Antiparasitic agents
Biological and medical sciences
Drug Stability
enantiotrope
enthalpy of solution
General pharmacology
Hot Temperature
hydrate
Medical sciences
monotrope
Pharmacology. Drug treatments
Physicochemical properties. Structure-activity relationships
polymorph
Solubility
Solutions - chemistry
sulfamerazine
Sulfamerazine - chemistry
Temperature
Thermodynamics
transition temperature
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Summary:The transition temperature, Tt, 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, ΔH, between polymorphs, I and II, is equal to the difference between their heats of solution, whereas the free energy difference, ΔG, can be estimated by the equation, ΔG=−RTln (cI/cII) or ΔG=−RTln (JI/JII), where c is the solubility and J is the intrinsic dissolution rate. The entropy difference, ΔS, is evaluated as (ΔH − ΔG)/T. Because the heat capacity difference,ΔCp between polymorphs is small enough to be neglected, the transition temperature may be estimated by the equation, Tt=ΔH/ΔS. The thermodynamic stability relationships of the polymorphs (i.e., whether they are enantiotropes or monotropes) are predicted from the value of Tt and the melting temperature. The Tt values for auranofin, carbamazepine, chloramphenicol palmitate, cyclopenthiazide, gepirone hydrochloride, lamivudine, MK571, premafloxacin, 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 Tt are in good agreement with those reported using other methods, such as differential scanning calorimetry and interpretation of melting data. © 2001 Wiley‐Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 90:1277–1287, 2001
ISSN:0022-3549
1520-6017
DOI:10.1002/jps.1080