Dehydration behavior of nedocromil magnesium pentahydrate.
The dehydration of nedocromil magnesium (NM) pentahydrate proceeds in two steps, corresponding to the loss of four water molecules in the first step and one water molecule in the second step. The effects of temperature, particle size, sample weight, water vapor pressure and dehydration-rehydration cycle on both the kinetics and activation energy of the dehydration of NM pentahydrate were studied using isothermal TGA and temperature-ramp DSC analyzed by Kissinger's method. The dehydration kinetics for both steps are best described by the Avrami-Erofeev equations, suggesting a nucleation-controlled mechanism. The high activation energy for the second dehydration step indicates that the last water molecule, which is bonded both to a magnesium ion and to a carboxylate oxygen atom, is more 'tightly bound'. The activation energy decreased with increasing sample weight and decreasing particle size. The dehydration rate increased with decreasing water vapor pressure and with repetition of the dehydration-hydration cycle. Dynamic and isothermal PXRD, and 13C solid-state NMR were employed to provide an insight into the dehydration mechanism and the nature of solid-state phase transformation during the dehydration. Molecular modeling with Cerius(2) was used to visualize the crystal structure and to construct the molecular packing diagram. A correlation was noted between the dehydration behavior and the bonding environment of the water molecules in the crystal structure.
Pharmaceutical Development Discovery Department, Glaxo Wellcome Inc., Research Triangle Park, NC 27709, USA. hjz40534@glaxowellcome.com
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Grant
D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003890:Desiccation; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008853:Microscopy; D008958:Models, Molecular; D008970:Molecular Weight; D017835:Nedocromil / Q000031:analogs & derivatives* / Q000737:chemistry*; D010316:Particle Size; D013696:Temperature; D014961:X-Ray Diffraction
D017835:Nedocromil