Influence of polyethylene glycol 4000 on the polymorphic forms of diflunisal

Abstract

The present study was carried out to investigate the physico-chemical characteristics of diflunisal–PEG 4000 solid dispersions prepared by melting, solvent and melting–solvent methods. The solvents chosen were chloroform, methanol and ethanol–water due to the fact that the drug presents different polymorphic forms in these solvents. The characterization of solid dispersions was performed by X-ray powder diffraction because this technique has the advantage over other identification methods that it can detect both drug and ligand simultaneously. The X-ray diffraction patterns of the diflunisal–PEG systems suggested that the drug/polymer ratio and the solvent nature play an important role in the crystallization of the drug. In this regard, diflunisal crystallizes in form I at high concentrations of the drug (drug/polymer 2:1) in the solidified melt dispersions, however, polymorph III is mainly obtained as the polymer content increases (1:1 and 2:3). Likewise, in solid systems obtained by the solvent and melting solvent methods the drug solidifies in form III in ethanol/water and methanol while polymorph IV crystallizes in chloroform. Finally, DSC thermograms and hot-stage microscopy data of solid dispersions prepared by the melting method have allowed to draw the diflunisal–PEG 4000 solid–liquid phase diagram.