Study of phase behavior of poly(ethylene glycol)-polysorbate 80 and poly(ethylene glycol)-polysorbate 80-water mixtures

Mixtures of poly(ethylene glycols) (PEGs) with polysorbate 80 are often use d to dissolve poorly water-soluble drugs in dosage forms, where polysorbate 80 helps either in enhancing dispersion or in inhibiting precipitation of drugs once the solution is mixed with water. Binary phase diagrams of polys orbate 80 with several low molecular weight PEGs and a ternary phase diagra m of polysorbate 80 with PEG 400 and water are presented. Two phases were o bserved in the binary mixtures when the concentration of PEG 200, PEG 300, PEG 400, or PEG 600 was >55%(w/w). The miscibility of the binary mixtures i ncreases with an increase in temperature; the upper consolute temperatures of PEG 200-polysorbate 80, PEG 300-polysorbate 80, PEG 400-polysorbate 80, and PEG 600-polysorbate 80 mixtures were 100, 85, 75, and 40 degrees C, res pectively. The upper consolute temperature of PEG 1000-polysorbate 80 could not be determined because the melting temperature of the mixtures is simil ar to 40 degrees C and the consolute temperature appeared to be less than t his temperature. The decrease in upper consolute temperature with an increa se in PEG molecular weight indicated a greater miscibility of the two compo nents. In the ternary system, phase separation of polysorbate 80 was observ ed when the concentration of PEG 400 was >50-60 % (w/w), possibly because o f the high exclusion volume of PEG 400. (C) 2000 Wiley-Liss, Inc. and the A merican Pharmaceutical Association.