Transitiometric analysis of solid II/solid I transition in anhydrous theophylline

For the first time, with the use of a high sensitivity, low heating rate, scanning transitiometry, it was possible to distinguish and characterise the polymorphic equilibrium transition between forms 11 and I in anhydrous theophylline. In this manner it was univocally proved, that forms 11 and I in theophylline, are enantiotropically related. The temperature and enthalpy for that transition are as follows: T-trs(II/I) = 536.8 +/- 2.2 K; Delta H-trs(II/I) = 1.99 +/- 0.09 kJ/mol. Making use of advantages of very slow heating rate and of a high energetic sensitivity of the transitiometer it was possible to observe in detail the polymorphic transition followed by melting of high temperature form I and to stop the solid I-liquid transition at a desired point of equilibrium. Such a solid I-liquid equilibrium could be stabilised and then displaced back to the crystallisation of form I with an adequate use of a precise temperature programming. In such a way a pure single phase of form I of theophylline was prepared. This fact was confirmed by X-ray powder diffraction patterns and calorimetric traces of fusion of the crystallised product. The temperature and enthalpy of the form I-liquid transition are as follows: T-fus(I) = 546.5 +/- 0.2 K and Delta H-fus(I) = 29.37 +/- 0.29 kJ/mol. (C) 2007 Elsevier B.V. All rights reserved.