A study on the preparation conditions of lidocaine microemulsion based on multi-objective genetic algorithm

Abstract

Background: Topical lidocaine microemulsion preparations with low toxicity, low irritation, strong transdermal capability and convenient administration are urgently needed.Methods: Box-Behnken design was performed for three preparation conditions of 5% lidocaine microemulsions: mass ratio of the mass ratio of surfactant/(oil phase + surfactant) (X1), the mass ratio of olive oil/(α-linolenic acid + linoleic acid) (X2) and the water content W% (X3). Then, five multi-objective genetic algorithms were used to optimize the three evaluation indices to optimize the effects of lidocaine microemulsion preparations. Finally, the ideal optimization scheme was experimentally verified.Results: Non-dominated Sorting Genetic Algorithm-II was used for 30 random searches. Among these, Scheme 2: X1 = 0.75, X2 = 0.35, X3 = 75%, which resulted in Y1 = 0.17 μg/(cm2·s) and Y2 = 0.74 mg/cm2; and the Scheme 19: X1 = 0.68, X2 = 1.42, X3 = 75% which resulted in Y1 = 0.14 μg/(cm2·s) and Y2 = 0.80 mg/cm2, provided the best matches for the objective function requirements. The maximum and average fitness of the method have reached stability after 3 generations of evolution. Experimental verification of the above two schemes showed that there were no statistically significant differences between the measured values of Y1 and Y2 and the predicted values obtained by optimization (p > 0.05) and are close to the target value.Conclusion: Two lidocaine microemulsion preparation protocols were proposed in this study. These preparations resulted in good transdermal performance or long anesthesia duration, respectively.