Influence of polyethylene glycol 4000 on the polymorphic forms of diflunisal

The present study was carried out to investigate the physico-chemical chara cteristics of diflunisal-PEG 4000 solid dispersions prepared by melting, so lvent and melting-solvent methods. The solvents chosen were chloroform, met hanol and ethanol-water due to the fact that the drug presents different po lymorphic forms in these solvents. The characterization of solid dispersion s was performed by X-ray powder diffraction because this technique has the advantage over other identification methods that it can detect both drug an d ligand simultaneously. The X-ray diffraction patterns of the diflunisal-P EG systems suggested that the drug/polymer ratio and the solvent nature pla y an important role in the crystallization of the drug. In this regard, dif lunisal crystallizes in form I at high concentrations of the drug (drug/pol ymer 2:1) in the solidified melt dispersions, however, polymorph III is mai nly obtained as the polymer content increases (1:1 and 2:3). Likewise, in s olid systems obtained by the solvent and melting solvent methods the drug s olidifies in form III in ethanol/water and methanol while polymorph IV crys tallized in chloroform. Finally, DSC thermograms and hot-stage microscopy d ata of solid dispersions prepared by;he melting method have allowed to draw the diflunisal-PEG 4000 solid-liquid phase diagram. (C) 1999 Elsevier Scie nce B.V. All, rights reserved.