Dynamic solid-state and tableting properties of four theophylline forms

Relationships between solid-state, densification and compact properties of theophylline monohydrate (TMO), a mixture of forms (TMIX), and anhydrous po lymorphs I (TA-I) and II (TA-II) were evaluated. Solid-state identification of powders and compacts was accomplished by powder X-ray diffraction. A co mpaction simulator was used to assess deformation behaviour of the powders and to prepare compacts. Porosity and tensile strength of the compacts were determined after 1, 24, and 168 h of storage at 22% relative humidity. TA- II was stable, whereas TA-I, TMIX and TMO partially transformed to the TA-I I form during storage. All theophylline modifications primarily deformed by plastic flow. Increased water content decreased resistance towards densifi cation and deformation of TMIX and TMO when compared to TA-II or TA-I, demo nstrating viscoelasticity. Permanent densification behaviours of TMIX and T MO approached to that of TA-II during storage. Tensile strength of the diff erent theophylline forms were practically equal after 1 h of storage. Tensi le strength and porosity of TMIX and TMO compacts increased during the stor age. Dynamic solid-state transformations from TMO, TMIX and TA-I to TA-II w ere associated with parallel changes in their densification and compact pro perties. The extent of these changes was also dependent on the materials' w ater content. (C) 2001 Elsevier Science B.V. All rights reserved.