MONITORING CRYSTAL MODIFICATIONS IN SYSTEMS CONTAINING IBUPROFEN

Qualitative and quantitative crystal analysis, including differential scanning calorimetry, X-ray powder diffraction and scanning electron microscopy were performed at different stages of ibuprofen tablet manufacture obtained at three levels of compaction. Melting points and enthalpy of fusion were carefully monitored and compared using statistical techniques (ANOVA and one degree of freedom procedures). Drug-disintegrant interactions were investigated using a fractional factorial design. Wetting and compaction affected the crystal surface as measured by a 0.2-8.6 kJ/mol decrease in the heat of fusion, and a shift of 2-3-degrees-C in the melting point. The differences were too small to suggest the existence of enantiotropically or monotropically related polymorphs. The results, however, indicated a lattice modification of ibuprofen during processing which we think occurred at the surface. The initial dissolution rates appeared to be inversely related to the amounts of ibuprofen in the formulation and the fastest drug release was obtained for a 1:3 intragranular ratio.