[learn_more caption=”Peter L.D. Wildfong”] Peter L.D. Wildfong,

Duquesne University[/learn_more]

Abstract:

Mechanical energy has been demonstrated to cause changes to the structure of small molecule organic materials during high shear secondary processing steps in pharmaceutical manufacturing. Here, PXRD and total scattering analysis was used to evaluate structural changes imparted on anyhydrous theophylline following compaction, either alone, or as part of a binary mixture with microcrystalline cellulose or lactose monohydrate. To prevent loss of structural information, intact compacts were evaluated in transmission mode PXRD, which allowed for full volume interrogation. Diffraction data attributable solely to theophylline was stripped from the patterns resulting from each PXRD experiment, and pair distribution function (PDF) transformed data was used to evaluation consolidation-related changes. Changes in the PDF patterns following consolidation were consistent with formation of regions of localized disorder, induced at pressures typical of pharmaceutical tableting operations. The role that the excipients played in preventing or facilitating localized disorder of the theophylline warrants future investigation. Disordering was observed for theophylline compacted in the presence of microcrystalline cellulose, however, little, if any structural changes were observed for theophylline compacted in the presence of lactose monohydrate.