Solubility of Acetaminophen in Cosolvents

Abstract

The solubilities of acetaminophen (N-(4-hydroxyphenyl)acetamide) (ACA) were determined in various aqueous cosolvent mixtures, i.e., ethanol-water, polyethylene glycol 400 (PEG 400)-water and polyethylene glycol 4000 (PEG 4000)-water, by ultraviolet spectrophotometry at 244 nm, a 30 ±2 C. The mixed solvents were prepared by mixing known volumes of solvents except in the case of PEG 4000-water where weight by volume (w/w) was used. In the above aqueous cosolvent systems, the solubility of ACA increased with cosolvent concentration and the maximum appeared at about 80% cosolvent concentration. When the solubilities of ACA were plotted against the approximate dielectric constants, which were calculated from the sum of the product of the volume composition with the dielectric constants of the individual components, peaks were found at dielectric constant values of 25 and 35 for PEG 400-water and ethanol-water, respectively. The solubility was fitted to a log linear solubility equation proposed by Yalkowski et al., which gave a good linear fit up to 40% cosolvent in all water-cosolvent mixtures. These results should be useful in the formulation of both oral and injectable ACA solutions. © 1984, The Pharmaceutical Society of Japan. All rights reserved.