Quantitative Structure-Activity Relationship of Enhancers of Licochalcone A and Glabridin Release and Permeation Enhancement from Carbomer Hydrogel

• Published in: Pharmaceutics Vol. 14; no. 2; p. 262
• Main Authors: Wang, Zhuxian, Xue, Yaqi, Zhu, Zhaoming, Hu, Yi, Zeng, Quanfu, Wu, Yufan, Wang, Yuan, Shen, Chunyan, Jiang, Cuiping, Liu, Li, Zhu, Hongxia, Liu, Qiang
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 22.01.2022; MDPI
• Subjects: Binding sites; Bond strength; carbomer hydrogel; Drug delivery systems; drug release and permeation; enhancement site and mechanism; enhancers; Hydrogels; Lipids; Pharmaceuticals; Polyethylene glycol; Retention; Rheology; Transdermal medication; Viscosity; whitening agents; Beijing China; New York; United States > US; China; drug release and permeation; carbomer hydrogel; enhancement site and mechanism; whitening agents; enhancers
• ISSN: 1999-4923; 1999-4923
• DOI: 10.3390/pharmaceutics14020262

This study aimed to systematically compare licochalcone A (LicA) and glabridin (Gla) (whitening agents) release and permeation from Carbomer 940 (CP) hydrogels with different enhancers, and evaluate the relationship between the quantitative enhancement efficacy and structures of the enhancers. An in vitro release study and an in vitro permeation experiment in solution and hydrogels using porcine skin were performed. We found that the Gla-CP hydrogel showed a higher drug release and skin retention amount than LicA-CP due to the higher solubility in medium and better miscibility with the skin of Gla than that of LicA. Enhancers with a higher molecular weight (MW) and lower polarizability showed a higher release enhancement effect (ER ) for both LicA and Gla. The Van der Waals forces in the drug-enhancers-CP system were negatively correlated with the drug release percent. Moreover, enhancers with a higher log P and polarizability displayed a higher retention enhancement effect in solution (ER ) for LicA and Gla. Enhancers decreased the whole intermolecular forces indrug-enhancers-skin system, which had a linear inhibitory effect on the drug retention. Moreover, C=O of ceramide acted asthe enhancement site for drug permeation. Consequently, Transcutol P (TP) and propylene glycol (PG), seven enhancers showed a higher retention enhancement effect in hydrogel (ER ) for LicA and Gla. Taken together, the conclusions provide a strategy for reasonable utilization of enhancers and formulation optimization in topical hydrogel whitening.