A Study of the Molecular Properties of Water in Hydrated Mannitol

• Published in: Journal of pharmaceutical sciences 2002-04, Vol.91 (4), p.1080-1088
• Main Authors: Derbyshire, Helen M., Feldman, Yuri, Bland, Chris R., Broadhead, Joanne, Smith, Geoff
• Format: Article
• Language: English
• Subjects: Analysis; Biological and medical sciences; Calorimetry, Differential Scanning; dielectric relaxation spectroscopy (DRS); differential scanning calorimetry (DSC); General pharmacology; mannitol; Mannitol - chemistry; Medical sciences; Microscopy, Electron, Scanning; near infrared spectroscopy (NIR); nuclear magnetic resonance spectroscopy (NMR); Nuclear Magnetic Resonance, Biomolecular; Pharmaceutical Preparations - chemistry; Pharmacology. Drug treatments; Spectroscopy, Near-Infrared; water; Water - chemistry; X-ray powder diffraction (XRPD)
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.10111

An understanding of the properties of water in hydrated saccharides and saccharide derivatives is relevant to a number of pharmaceutical processes, including wet granulation. This study uses a range of physical measurement techniques [viz. nuclear magnetic resonance spectroscopy (NMR), dielectric relaxation spectroscopy (DRS), near infrared spectroscopy (NIR), and differential scanning calorimetry (DSC)] to analyze the molecular properties of water in hydrated mannitol (containing up to 0.45 g water per gram of dry sample). The resulting measurements show a correlation between the different techniques, in that each technique shows two transitions (ht1 and ht2) in the properties of the hydrated material (at water contents of ∼0.1 g/g and 0.25–0.3 g/g, respectively). It is suggested that ht1 and ht2 mark the appearance of a second and a third population of water and that these transitions are due to different stages of microdissolution of the solid. Evidence is presented that shows that this second population of water undergoes a thermodynamic phase transition close to 0°C, and therefore the material must contain some water that is behaving like free water. The significance of the transitions (ht1 and ht2) and the mobility of water (above and below these transitions) are yet to be established for mixtures of sugars and other materials. However, it is probable that this information will contribute to our understanding of the how these types of materials are processed (e.g., during the wet granulation process) and how drugs maintain their stability during processes that involve the significant hydration of a powder blend. © 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:1080–1088, 2002