Kinetics and optimization of lipophilic kojic acid derivative synthesis in polar aprotic solvent using lipozyme RMIM and its rheological study

• Main Authors: Ishak, Nurazwa, Lajis, Ahmad, Mohamad, Rosfarizan, Ariff, Arbakariya, Mohamed, Mohd Shamzi, Halim, Murni, Wasoh, Helmi
• Format: Article
• Language: English
• Published: MDPI AG 2018
• Online Access: http://psasir.upm.edu.my/id/eprint/74790/1/Kinetics%20and%20optimization%20of%20lipophilic%20kojic%20acid%20derivative%20synthesis%20in%20polar%20aprotic%20solvent%20using%20lipozyme%20RMIM%20and%20its%20rheological%20study.pdf; http://psasir.upm.edu.my/id/eprint/74790/; https://www.mdpi.com/1420-3049/23/2/501

The synthesis of kojic acid derivative (KAD) from kojic and palmitic acid (C16:0) in the presence of immobilized lipase from Rhizomucor miehei (commercially known as Lipozyme RMIM), was studied using a shake flask system. Kojic acid is a polyfunctional heterocycles that acts as a source of nucleophile in this reaction allowing the formation of a lipophilic KAD. In this study, the source of biocatalyst, Lipozyme RMIM, was derived from the lipase of Rhizomucor miehei immobilized on weak anion exchange macro-porous Duolite ES 562 by the adsorption technique. The effects of solvents, enzyme loading, reaction temperature, and substrate molar ratio on the reaction rate were investigated. In one-factor-at-a-time (OFAT) experiments, a high reaction rate (30.6 × 10−3 M·min−1) of KAD synthesis was recorded using acetone, enzyme loading of 1.25% (w/v), reaction time of 12 h, temperature of 50 °C and substrate molar ratio of 5:1. Thereafter, a yield of KAD synthesis was optimized via the response surface methodology (RSM) whereby the optimized molar ratio (fatty acid: kojic acid), enzyme loading, reaction temperature and reaction time were 6.74, 1.97% (w/v), 45.9 °C, and 20 h respectively, giving a high yield of KAD (64.47%). This condition was reevaluated in a 0.5 L stirred tank reactor (STR) where the agitation effects of two impellers; Rushton turbine (RT) and pitch-blade turbine (PBT), were investigated. In the STR, a very high yield of KAD synthesis (84.12%) was achieved using RT at 250 rpm, which was higher than the shake flask, thus indicating better mixing quality in STR. In a rheological study, a pseudoplastic behavior of KAD mixture was proposed for potential application in lotion formulation.