DEHYDRATION OF THEOPHYLLINE MONOHYDRATE - A 2-STEP PROCESS

The physicochemical properties of theophylline monohydrate and anhydro us polymorphic form II were evaluated using crystallographic, calorime tric and computational methods. The heats of solution of theophylline monohydrate and its anhydrous form were 28.6 and 19.4 kJ/mol, respecti vely, and the heat of hydration of theophylline anhydrous was 12.2 kJ/ mol, as determined by solution calorimetry. Dehydration of theophyllin e monohydrate was studied by DSC. Under closed, hermetic conditions, t he heat of dehydration, 10.7 kJ/mol, was almost equal to the heat of h ydration. Under open conditions, the measured heat of dehydration was 47.3 kJ/mol. The dehydration phenomenon was examined also by molecular modelling and the computed heat changes were equal to those determine d experimentally. The obtained experimental and theoretical results in dicated that the monohydrate-anhydrate transition of theophylline is e nergetically reversible. Under closed conditions and in the aqueous me dia, the reversible monohydrate-anhydrate transition comprised only th e dehydration or hydration step and the heat of transitions were consi derably lower than under open conditions. Under open conditions, the d ehydration of theophylline monohydrate proceeds in two steps even thou gh the steps are overlapping. The first step is dehydration and the se cond is evaporation of the loosened crystal water. (C) 1997 Elsevier S cience B.V.