The dehydration kinetics of theophylline monohydrate powder and tablet.

The dehydration of theophylline monohydrate in powder and tablet forms was studied by using an infrared water-content measuring instrument.Intact theophylline powder was recrystallized from distilled water,and ground powder was obtained by grinding in a ceramic mortar with a pestle.The samples were dehydrated as follows.The intact and ground powders were placed on a plate8cm in diameter.A powder bed was formed on a plate 3cm in diameter as a model of a loosely packed tablet,and a tablet2.0cm in diameter was obtained by compression at 1.0t/cm2. Dehydration kinetic mechanisms of various dosage forms of theophylline monohydrate were clarified by using various kinds of solid-state kinetic models.The dehydrations of intact and ground powders followed two-dimensional growth of nuclei and three-dimensional growth of nuclei equations,and the activation energies(Ea)were 20.1 and 23.0 kcal/mol,respectively.The dehydrations of powder bed and tablet followed two-dimensional phase boundary and threedimensional phase boundary equations,and the Ea values were 15.4 and 11.5 kcal/mol,respectively. It seems that the dehydration of intact powder starts randomly at each particle and proceeds two dimensionally,but that of ground crystals proceeds three-dimensionally from the cracks in particles.In the case of the powder bed the dehydration proceeds two-dimensionally from the surface particles of the powder bed into the inner particles.The dehydration of a tablet proceeds three-dimensionally from the outside of the tablet into its inside. Keywords-theophylline;hydrate;thermal kinetics;dehydration;dosage form