Evaluation of Direct Esterification of Fatty Acid Derivative of Kojic Acid in Co-solvent System: A Statistical Approach

Abstract

The present work deals with direct esterification method to synthesize Kojic acid using immobilized lipase as a biocatalyst in acetonitrile with the addition of dimethylsulfoxide (DMSO) as a solubilizing agent Co-solvent respectively. To increase the esterification yield of KMO, modifications of the process were evaluated, including the use of a cosolvent and the use of Novozyme 435 (Candida antarctica) as a catalyst. The KMO synthesis has been developed and optimized by using Response Surface Methodology (RSM) with Central Composite Rotatable Design (CCRD). The optimized condition of enzyme was 3.35 wt% and 1:3.64 molar ratio of kojic acid and oleic acid at 82.39°C for 255.24 min of reaction. With these condition, the maximum percentage yield was 42.73% with R2 value of 0.866914 and indicated that 86.69% of the variability in the response could be explained by the model. The model was significant and fitted well with the experimental data and the lack of fit was not significant. The efficacy for cosmetic application was successfully tested and showed as non-irritating with a Human Irritancy Equivalent score between 0.55-0.83 which safe to be applied in cosmetic ingredient.

An Improved Nanoemulsion Formulation Containing Kojic Monooleate: Optimization, Characterization and In Vitro Studies

“…The process parameters involved in producing nanoemulsion should be optimized in order to obtain the desired droplet size. The conventional method (one factor at a time) is time-consuming and costly [33]. The desired droplet size of nanoemulsion can be optimized by using Response Surface Methodology (RSM).…”

In vitro Kinetic Release Study, in vivo Hydration and Moisturizing Effect of Peel-off Oil-in-Water (O/W) Nanoemulsion Containing Kojic Monooleate for Topical Application

“…15 A potent tyrosinase inhibitor, the metabolite kojic acid (5-hydroxymethyl)-1, 4-pyrone is produced by fungus, such as Aspergillus, Acetobacter, and Penicilium. [16][17][18] Kojic monooleate (KMO) is a derivative of kojic acid that improves the storage instability, oilsolubility, and toxicity of kojic acid. [16][17][18][19] KMO was also found to be a better tyrosinase inhibitor compared to kojic acid and exhibits strong antioxidant activity.…”

Regioselective Enzymatic Synthesis of Kojic Acid Monoesters

“…Free kojic acid is rather instable at ambient conditions. Several attempts have been made to improve its stability and water-solubility by enzymatic glycosylation [6][7][8][9][10][11], and also to widen its use in oil-based foods and cosmetic products by lipase catalyzed esterification [5,[12][13][14][15][16][17][18][19][20][21][22][23][24]. Data on the enzymatic esterification (which is in fact an acylation) of kojic acid are, however, rather confusing with respect to the regioselectivity of the reaction.…”

“…Data on the enzymatic esterification (which is in fact an acylation) of kojic acid are, however, rather confusing with respect to the regioselectivity of the reaction. For example, Kobayashi et al [18] published a paper on the semi-continual production of kojic 7-laurate by the direct esterification of kojic acid with free lauric acid using lipase from Free kojic acid is rather instable at ambient co made to improve its stability and water-solubility by also to widen its use in oil-based foods and cosmeti fication [5,[12][13][14][15][16][17][18][19][20][21][22][23][24]. Data on the enzymatic esterificat kojic acid are, however, rather confusing with resp tion.…”