The dehydration kinetics of theophylline monohydrate powder and tablet.

Abstract

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 plate 8cm in diameter. A powder bed was formed on a plate 3cm in diameter as a model of a loosely packed tablet, and a tablet 2.0cm 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.