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 II and I in anhydrous theophylline. In this manner it was univocally proved, that forms II and I in theophylline are enantiotropically related. The temperature and enthalpy for that transition are as follows: Ttrs(II/I) = 536.8 ± 2.2 K; ΔtrsH(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: Tfus(I) = 546.5 ± 0.2 K and ΔfusH(I) = 29.37 ± 0.29 kJ/mol.