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: T(trs)(II/I)=536.8+/-2.2K; Delta(trs)H(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+/-0.2K and Delta(fus)H(I)=29.37+/-0.29 kJ/mol.
Legendre
Bernard
B
Laboratoire de Chimie Physique Minérale et Bioinorganique, EA 401, Faculté de Pharmacie, 5 rue J.B. Clément, 92290 Châtenay, Malabry, France.
Randzio
Stanislaw L
SL
D002152:Calorimetry, Differential Scanning; D006358:Hot Temperature; D044367:Phase Transition; D033362:Powder Diffraction; D013806:Theophylline / Q000737:chemistry*; D014961:X-Ray Diffraction
D013806:Theophylline