An investigation into the thermal behaviour of a model drug mixture with amorphous trehalose.

The thermal and structural properties of amorphous trehalose mixed with a model drug, paracetamol, have been studied with a view to developing understanding of the thermal events undergone by such binary systems. A physical mixture of paracetamol and spray dried trehalose (1:9 weight ratio) was studied using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), hot stage microscopy (HSM), and variable temperature powder X-ray diffraction (VTPXRD). The presence of the drug resulted in a lower temperature recrystallization exotherm for the trehalose compared to the disaccharide alone. Evidence is presented for the trehalose recrystallization being triggered by the melting rather than simply the presence of the paracetamol particles. HSM studies indicated that the trehalose recrystallized around the drug on heating, with the recrystallization temperature again corresponding to the melting of the drug. VTPXRD indicated that the presence of the drug again lowered the recrystallization temperature of the trehalose, although the trehalose anhydrate diffraction peaks were discernible at a lower temperature for both the pure trehalose and the mixed systems than was observed for the DSC studies, suggesting that the association between recrystallization and drug melting was not apparent when using this approach. It is suggested that while the trehalose recrystallization process is not significantly influenced by the presence of the drug when studied over relatively long time periods such as those used for the VTPXRD studies, the process is triggered by the melting of the paracetamol when short experimental times and scanning conditions are used such as those relevant to DSC studies. These data have implications for the quality control of trehalose products using DSC, the characterisation of the physical structure of the binary systems and the prediction of the corresponding physical stability.

2,8-Dihydroxy-1,3,7,9-tetramethyl-6,12-dihydrodipyrido

The 2,8-dihydroxy-1,3,7,9-tetramethyl-6,12-dihydrodipyrido[1,2-a:1', 2'-d]pyrazinediylium dication possesses 2/m symmetry and lies in the mirror plane together with a chloride anion and the water O atom. The dication also lies on an inversion centre, i.e. C(16)H(20)N(2)O(2)(2+).2Cl(-).2H(2)O. Due to these symmetry constrictions the dication adopts an unexpected planar conformation. Molecules are linked by O-H.O and O-H.Cl hydrogen bonds to form chains, which are cross-connected by C-H.Cl attractive interactions forming a complex three-dimensional hydrogen-bond network.