Paracetamol-propyphenazone interaction and formulation difficulties associated with eutectic formation in combination solid dosage forms

Polymorphic behaviours of paracetamol and propyphenazone and interaction be tween these two compounds were investigated using differential scanning cal orimetry (DSC), X-ray powder diffraction and Fourier transform-infrared (FT -IR)-spectroscopy. Binary mixtures containing various ratios of the compoun ds were prepared as physical and fused mixtures and analysed by DSC to stud y their thermal behaviours, Phase diagrams obtained from the melting endoth erms of the binary mixtures demonstrated formation of an eutectic mixture a t a paracetamol-propyphenazone combination of about 35 : 65 (w/w) with an e utectic temperature of 56 degrees C. The FT-IR spectroscopy revealed no che mical interaction due to eutectic formation, and a lower degree of crystall inity of the eutectic mixture than individual substances was observed by X- ray powder diffraction analysis. The DSC and X-ray powder diffraction data demonstrated a polymorphic change in propyphenazone as a result of melting of the compound. Tablets, containing both paracetamol and propyphenazone in a combination formulation and prepared using standard wet granulation tech nology, were found to have physical instability when packed in either polyv inylchloride//aluminium or polyvinylchloride/polyvinyldienechloride//alumin ium blisters and stored for one month at 40 degrees C with either 75% relat ive humidity or without any humidity control. The instability of the tablet s was more apparent under the high humidity condition.