AUTHOR=Qiao Yuchao , Wang Xuchun , Ren Hao , Cui Yu , Ren Jiahui , Hao Chongqi , Zhao Zhiyang , Liu Jing , Zhao Ruiqing , Li Yiting , Tian Qingping , Qiu Lixia 

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

JOURNAL=Frontiers in Pharmacology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1272454

DOI=10.3389/fphar.2023.1272454

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> Topical lidocaine microemulsion preparations with low toxicity, low irritation, strong transdermal capability and convenient administration are urgently needed.</p><p><bold>Methods:</bold> Box-Behnken design was performed for three preparation conditions of 5% lidocaine microemulsions: mass ratio of the mass ratio of surfactant/(oil phase + surfactant) (X<sub>1</sub>), the mass ratio of olive oil/(α-linolenic acid + linoleic acid) (X<sub>2</sub>) and the water content W% (X<sub>3</sub>). 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.</p><p><bold>Results:</bold> Non-dominated Sorting Genetic Algorithm-II was used for 30 random searches. Among these, Scheme 2: X<sub>1</sub> = 0.75, X<sub>2</sub> = 0.35, X<sub>3</sub> = 75%, which resulted in Y<sub>1</sub> = 0.17 μg/(cm<sup>2</sup>·s) and Y<sub>2</sub> = 0.74 mg/cm<sup>2</sup>; and the Scheme 19: X<sub>1</sub> = 0.68, X<sub>2</sub> = 1.42, X<sub>3</sub> = 75% which resulted in Y<sub>1</sub> = 0.14 μg/(cm<sup>2</sup>·s) and Y<sub>2</sub> = 0.80 mg/cm<sup>2</sup>, 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 Y<sub>1</sub> and Y<sub>2</sub> and the predicted values obtained by optimization (<italic>p</italic> &gt; 0.05) and are close to the target value.</p><p><bold>Conclusion:</bold> Two lidocaine microemulsion preparation protocols were proposed in this study. These preparations resulted in good transdermal performance or long anesthesia duration, respectively.</p>