Solvation mechanisms of nedocromil sodium from activation energy and reaction enthalpy measurements of dehydration and dealcoholation

• Published in: Journal of pharmaceutical sciences Vol. 91; no. 4; p. 1101
• Main Authors: Richards, Alison C, McColm, Ian J, Harness, J Barrie
• Format: Journal Article
• Language: English
• Published: United States 01-04-2002
• Subjects: Anti-Allergic Agents - chemistry; Desiccation - methods; Nedocromil - chemistry; Solvents - chemistry; Temperature
• ISSN: 0022-3549
• DOI: 10.1002/jps.10047

Two independent athermal methods of analysis have been used to determine the activation energies associated with the dehydration of nedocromil sodium hydrates. For the highest temperature reaction, monohydrate to the anhydrate, the differences in the measured activation energies indicate a three-dimensional nucleation mechanism in the bulk of the crystal with subsequent three-dimensional anhydrate crystal growth. The number of critical nuclei varies inversely with heating rate. Measured enthalpy values for successive removal of water molecules at 31.7 +/- 1.0, 91.3 +/- 0.8, and 193 +/- 0.6 degrees C are the same, within experimental error, at 21.6 +/- 2.6 kJ (mol H(2)O)(-1), as determined from differential thermal analysis traces. This result implies that an earlier concept of "strong" and "weak" water binding is not relevant and temperatures at which H(2)O molecules are removed is related to nucleation effects and not bond energies. The low temperature shoulder on the 91.3 degrees C peak is identified as an effect arising from open pan analysis conditions. The appearance of "transient" peaks in the conditioning stage of nedocromil sodium trihydrate thermal analysis experiments have been investigated and an explanation based on the presence of alcoholates [(NS)(4) small middle dot 5CH(3)OH, (NS)(5) small middle dot 9C(2)H(5)OH, and (NS)(2) small middle dot C(3)H(7)OH] in the preparations is proposed.