Influence of Temperature on Solvent-Mediated Anhydrate-to-Hydrate Transformation Kinetics
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.
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.
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.
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.
KEY WORDSanhydrate-to-hydrate crystallization phase transformation supersaturation
Financial support from the Danish Council for Independent Research, Technology and Production Sciences (Project No. 274-09-0028) is acknowledged. Lundbeckfonden (Denmark, project No. 479/06) is acknowledged for the financial support of XRPD instrument.
- 1.Morris KR. Structural aspects of hydrates and solvates. In: Brittain HG, editor. Polymorphism in pharmaceutical solids. New York: Marcel Dekker, Inc; 1999. p. 125–81.Google Scholar
- 3.Grant DJW, Higuchi T. Solubility behavior of organic compounds. New York: Willey; 1990.Google Scholar
- 10.Krahn FU, Mielck JB. Relations between several polymorphic forms and the dihydrate of carbamazepine. Pharm Acta Hel. 1987;62:247–54.Google Scholar
- 12.Reboul PJ, Cristau B, Soyfer JC. 5H-Dibenz[b, f]azepine-5-carboxamide (carbamazepine). Acta Crystallogr. 1981;B37:1844–8.Google Scholar
- 13.Mihalic M, Hofman H, Kajfez F, Kuftinec J, Blazvic N, Zinic M. Physico-chemical and analytical characteristics of piroxicam. Acta Pharm Jugosl. 1982;32:13–20.Google Scholar
- 18.Wu JX, Tian F, Cornett C, Munk T, Savolainen M, Rantanen J. Building a robust quantitative model for process monitoring of solid state transformation AAPS Annual meeting Nov 8–12. USA: Los Angeles; 2009.Google Scholar
- 20.Draper NR, Smith H. Applied regression analysis, Wiley, ISBN: 0-471-02995-5, 1981.Google Scholar
- 27.Mullin JW. Crystallization. Oxford: Butterworth-Heinemann; 2001.Google Scholar