Time temperature indicators made with sublimating azulene derivatives as the functional dye for use of fast reaction rate

Abstract

Time temperature indicators (TTIs) based on a dye sublimation process have been developed for full time monitoring of heat sensitive vaccines with shorter shelf‐life during cold chain transportation and storage. The structure of TTI and the methods to make the TTI are introduced. TTI 1 and TTI 2 introduced in the article were made with methyl azulene‐1‐carboxylate and methyl 3‐methylazulene‐1‐carboxylate as the functional dyes, respectively. The kinetic parameters of TTI 1 and TTI 2 were studied. To achieve a change of 30 in ∆E*ab, it takes 9.1 h at 37°C, 39.7 h at 25°C, 5.61 days at 15°C and 23.3 days at 5°C for TTI 1 and 37.2 h at 37°C, 128.8 h at 25°C, 37.5 days at 15°C and 102.5 days at 5°C for TTI 2. The activation energies (Ea) are calculated to be 91.87 kJ mol−1 and 97.99 kJ mol−1 for TTI 1 and TTI 2, respectively. A field simulation study was conducted on TTI 2 associated with bivalent oral polio vaccine (bOPV), yielding excellent correlation between the reaction rate of TTI 2 and the titre change of bOPV.