Dehydration of trehalose dihydrate at low relative humidity and ambient temperature.
The physico-chemical behaviour of trehalose dihydrate during storage at low relative humidity and ambient temperature was investigated, using a combination of techniques commonly employed in pharmaceutical research. Weight loss, water content determinations, differential scanning calorimetry and X-ray powder diffraction showed that at low relative humidity (0.1% RH) and ambient temperature (25 degrees C) trehalose dihydrate dehydrates forming the alpha-polymorph. Physical examination of trehalose particles by scanning electron microscopy and of the dominant growth faces of trehalose crystals by environmentally controlled atomic force microscopy revealed significant changes in surface morphology upon partial dehydration, in particular the formation of cracks. These changes were not fully reversible upon complete rehydration at 50% RH. These findings should be considered when trehalose dihydrate is used as a pharmaceutical excipient in situations where surface properties are key to behaviour, for example as a carrier in a dry powder inhalation formulations, as morphological changes under common processing or storage conditions may lead to variations in formulation performance.
Jones
Matthew D
MD
Pharmaceutical Surface Science Research Group, Department of Pharmacy and Pharmacology, University of Bath, Bath BA2 7AY, UK.
Hooton
Jennifer C
JC
Dawson
Michelle L
ML
Ferrie
Alan R
AR
Price
Robert
R
D002152:Calorimetry, Differential Scanning; D018360:Crystallography, X-Ray; D003890:Desiccation; D005079:Excipients / Q000737:chemistry*; D006813:Humidity; D018625:Microscopy, Atomic Force; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D013499:Surface Properties; D013696:Temperature; D014199:Trehalose / Q000737:chemistry*; D014867:Water / Q000737:chemistry
D005079:Excipients; D014867:Water; D014199:Trehalose