Unusual Effect of Water Vapor Pressure on Dehydration of Dibasic Calcium Phosphate Dihydrate

Dibasic calcium phosphate occurs as an anhydrate (DCPA; CaHPO4) and as a dihydrate (DCPD; CaHPO4 center dot 2H(2)O). Our objective was to investigate the unusual behavior of these phases. Dibasic calcium phosphate dihydrate was dehydrated in a (i) differential scanning calorimeter (DSC) in different pan configurations; (ii) variable-temperature X-ray diffractometer (XRD) at atmospheric and under reduced pressure, and in sealed capillaries; and (iii) water vapor sorption analyzer at varying temperature and humidity conditions. Dehydration was complete by 210 degrees C in an open DSC pan and under atmospheric pressure in the XRD. Unlike "conventional" hydrates, the dehydration of DCPD was facilitated in the presence of water vapor. Variable-temperature XRD in a sealed capillary and DSC in a hermetic pan with pinhole caused complete dehydration by 100 degrees C and 140 degrees C, respectively. Under reduced pressure, conversion to the anhydrate was incomplete even at 300 degrees C. The increase in dehydration rate with increase in water vapor pressure has been explained by the Smith-Topley effect. Under "dry" conditions, a coating of poorly crystalline product is believed to form on the surface of particles and act as a barrier to further dehydration. However, in the presence of water vapor, recrystallization occurs, creating cracks and channels and facilitating continued dehydration. (c) 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:1456-1466, 2011