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 polymorphs I (TA-I) and II (TA-II) were evaluated. Solid-state identification of powders and compacts was accomplished by powder X-ray diffraction. A compaction 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-II form during storage. All theophylline modifications primarily deformed by plastic flow. Increased water content decreased resistance towards densification and deformation of TMIX and TMO when compared to TA-II or TA-I, demonstrating viscoelasticity. Permanent densification behaviours of TMIX and TMO approached to that of TA-II during storage. Tensile strength of the different theophylline forms were practically equal after 1 h of storage. Tensile strength and porosity of TMIX and TMO compacts increased during the storage. Dynamic solid-state transformations from TMO, TMIX and TA-I to TA-II were associated with parallel changes in their densification and compact properties. The extent of these changes was also dependent on the materials' water content.
Suihko
E
E
Department of Pharmaceutics, University of Kuopio, PO Box 1627, FIN-70211, Kuopio, Finland. eero.suihko@uku.fi
Lehto
V P
VP
Ketolainen
J
J
Laine
E
E
Paronen
P
P
D001993:Bronchodilator Agents / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D019245:Compressive Strength; D004356:Drug Storage; D016062:Porosity; D011208:Powders; D013607:Tablets; D013718:Tensile Strength; D013806:Theophylline / Q000737:chemistry*; D014867:Water / Q000032:analysis*; D014961:X-Ray Diffraction
D001993:Bronchodilator Agents; D011208:Powders; D013607:Tablets; D014867:Water; D013806:Theophylline