title: Influence of temperature on solvent-mediated anhydrate-to-hydrate transformation kinetics.
abstract: OBJECTIVE
  To achieve an in-depth understanding of the underlying mechanism of the acceleration or deceleration effect of temperature on solvent-mediated anhydrate-to-hydrate phase transformation.
  
  
  METHODS
  The effect of temperature on the phase transformation rate and onset time of two model compounds was investigated using in situ Raman spectroscopy. The thermodynamic driving force of the phase transformation (e.g. supersaturation) at different temperatures was determined by measuring the solubility of the anhydrate and the hydrate.
  
  
  RESULTS
  Both acceleration and deceleration effects of temperature on the phase transformation were observed. The mechanism of these temperature effects was studied by exploring the influence of temperature on supersaturation level and crystallization kinetics. Increasing temperature usually leads to accelerated phase transformation kinetics, but it simultaneously decreases supersaturation, which has the opposite effect on the kinetics of the phase transformation. The overall effect of temperature on the phase transformation is therefore determined by the combined effects of supersaturation and temperature on the nucleation and crystal growth kinetics of the hydrate.
  
  
  CONCLUSIONS
  By differentiating and comparing the effects of temperature and supersaturation on the anhydrate-to-hydrate phase transformation, a deeper understanding of the underlying principle of the acceleration and deceleration effects of temperature on the phase transformation has been achieved.
authors.affiliation: Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen Ø, Denmark. haq@kbm.sdu.dk
authors.forename: Haiyan
authors.initials: H
authors.lastname: Qu
authors.forename: Tommy
authors.initials: T
authors.lastname: Munk
authors.forename: Claus
authors.initials: C
authors.lastname: Cornett
authors.forename: Jian X
authors.initials: JX
authors.lastname: Wu
authors.forename: Johan P
authors.initials: JP
authors.lastname: Bøtker
authors.forename: Lars P
authors.initials: LP
authors.lastname: Christensen
authors.forename: Jukka
authors.initials: J
authors.lastname: Rantanen
authors.forename: Fang
authors.initials: F
authors.lastname: Tian
mesh_terms: D002220:Carbamazepine / Q000737:chemistry*; D003460:Crystallization; D004355:Drug Stability; D007700:Kinetics; D008956:Models, Chemical; D044367:Phase Transition; D010894:Piroxicam / Q000737:chemistry*; D012995:Solubility; D012997:Solvents; D013059:Spectrum Analysis, Raman; D013678:Technology, Pharmaceutical / Q000379:methods; D013696:Temperature; D013816:Thermodynamics
chemical_list: D012997:Solvents; D010894:Piroxicam; D002220:Carbamazepine