title: Prediction of color changes in acetaminophen solution using the time-temperature superposition principle.
abstract: A prediction method for color changes based on the time-temperature superposition principle (TTSP) was developed for acetaminophen solution. Color changes of acetaminophen solution are caused by the degradation of acetaminophen, such as hydrolysis and oxidation. In principle, the TTSP can be applied to only thermal aging. Therefore, the impact of oxidation on the color changes of acetaminophen solution was verified. The results of our experiment suggested that the oxidation products enhanced the color changes in acetaminophen solution. Next, the color changes of acetaminophen solution samples of the same head space volume after accelerated aging at various temperatures were investigated using the Commission Internationale de l'Eclairage (CIE) LAB color space (a*, b*, L* and ΔE*ab), following which the TTSP was adopted to kinetic analysis of the color changes. The apparent activation energies using the time-temperature shift factor of a*, b*, L* and ΔE*ab were calculated as 72.4, 69.2, 72.3 and 70.9 (kJ/mol), respectively, which are similar to the values for acetaminophen hydrolysis reported in the literature. The predicted values of a*, b*, L* and ΔE*ab at 40 °C were obtained by calculation using Arrhenius plots. A comparison between the experimental and predicted values for each color parameter revealed sufficiently high R(2) values (>0.98), suggesting the high reliability of the prediction. The kinetic analysis using TTSP was successfully applied to predicting the color changes under the controlled oxygen amount at any temperature and for any length of time.
authors.affiliation: a Department of Pharmaceutics , Hoshi University , 2-4-41 Ebara , Shinagawa-ku , Tokyo , Japan ;|b Oral Formulation Laboratory , R & D Laboratories, Self Medication Business, Taisho Pharmaceutical Co. Ltd , 1-403 Yoshino-Cho, Kita-Ku , Saitama Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Mochizuki
authors.affiliation: a Department of Pharmaceutics , Hoshi University , 2-4-41 Ebara , Shinagawa-ku , Tokyo , Japan ;
authors.forename: Kozo
authors.initials: K
authors.lastname: Takayama
mesh_terms: D000082:Acetaminophen / Q000737:chemistry / Q000592:standards*; D002626:Chemistry, Pharmaceutical; D003116:Color; D004355:Drug Stability; D007700:Kinetics; D010084:Oxidation-Reduction; D010100:Oxygen / Q000032:analysis; D019999:Pharmaceutical Solutions / Q000737:chemistry / Q000592:standards; D011237:Predictive Value of Tests; D013696:Temperature
chemical_list: D019999:Pharmaceutical Solutions; D000082:Acetaminophen; D010100:Oxygen
keywords: Arrhenius plots; acetaminophen; color change; kinetic analysis; pharmaceutical development; prediction; quality control; time–temperature superposition principle