Study of Phase Behavior of Poly(ethylene glycol)–Polysorbate 80 and Poly(ethylene glycol)–Polysorbate 80–Water Mixtures

• Published in: Journal of pharmaceutical sciences Vol. 89; no. 7; pp. 946 - 950
• Main Authors: Tejwani, Ravindra W., Joshi, Hemant N., Varia, Sailesh A., Serajuddin, Abu T.M.
• Format: Journal Article
• Language: English
• Published: New York Elsevier Inc 01.07.2000; John Wiley & Sons, Inc; Wiley; American Pharmaceutical Association
• Subjects: Biological and medical sciences; consolute temperature; dosage form; Dosage Forms; Excipients - chemistry; General pharmacology; Medical sciences; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; phase diagram; phase separation; poly(ethylene glycol); Polyethylene Glycols - chemistry; polysorbate 80; Polysorbates - chemistry; solubility; Temperature; consolute temperature; dosage form; polysorbate 80; phase diagram; phase separation; poly(ethylene glycol); solubility; Water; Ethylene oxide polymer; Temperature; Pharmaceutical technology; Phase diagram; Phase separation; Dosage form; Miscibility; Drug carrier; Molecular weight; Physicochemical properties
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/1520-6017(200007)89:7<946::AID-JPS12>3.0.CO;2-2

Mixtures of poly(ethylene glycols) (PEGs) with polysorbate 80 are often used 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 polysorbate 80 with several low molecular weight PEGs and a ternary phase diagram of polysorbate 80 with PEG 400 and water are presented. Two phases were observed 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 increases 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 °C, respectively. The upper consolute temperature of PEG 1000–polysorbate 80 could not be determined because the melting temperature of the mixtures is ∼40 °C and the consolute temperature appeared to be less than this temperature. The decrease in upper consolute temperature with an increase in PEG molecular weight indicated a greater miscibility of the two components. In the ternary system, phase separation of polysorbate 80 was observed when the concentration of PEG 400 was >50–60 % (w/w), possibly because of the high exclusion volume of PEG 400. © 2000 Wiley‐Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 89:946–950, 2000