Physicochemical Properties and Transdermal Absorption of a Flurbiprofen and Lidocaine Complex in the Non-Crystalline Form

Qihui Xu; Takayuki Furuishi; Kaori Fukuzawa; Etsuo Yonemochi

doi:10.3390/pharmaceutics15020318

Physicochemical Properties and Transdermal Absorption of a Flurbiprofen and Lidocaine Complex in the Non-Crystalline Form

Pharmaceutics. 2023 Jan 18;15(2):318. doi: 10.3390/pharmaceutics15020318.

Authors

Qihui Xu¹, Takayuki Furuishi¹, Kaori Fukuzawa^{1

2}, Etsuo Yonemochi¹

Affiliations

¹ Department of Physical Chemistry, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
² Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita 565-0871, Japan.

Abstract

Amorphous drug formulations exploiting drug-drug interactions have been extensively studied. This study aims to develop a transdermal system containing an amorphous complex of the nonsteroidal anti-inflammatory drug (NSAID) flurbiprofen (FLU) and lidocaine (LDC) for alleviating chronic pain. The high-viscosity complex between FLU and LDC (Complex) was obtained by heating in ethanol. For the complex, attenuated total reflection-Fourier transform infrared spectroscopy showed a shift in the carboxy-group-derived peak of FLU, and differential scanning calorimetry indicated the endothermic peaks associated with the melting of FLU and LDC disappeared. ¹³C dipolar decoupling and ¹⁵N cross-polarization magic-angle spinning nuclear magnetic resonance measurement suggested the interaction between the carboxyl group of FLU and the secondary amine of LDC. The interaction between the aromatic rings of FLU and LDC contributed to the molecular complex formation. The solubility of FLU from the complex was about 100 times greater than FLU alone. The skin permeation flux of FLU from the complex through the hairless mouse skin was 3.8 times higher than FLU alone in hypromellose gel. Thus, adding LDC to the formulation can be an effective method for enhancing the skin permeation of NSAIDs, which can prove useful for treating chronic pain and inflammatory diseases.

Keywords: amorphous; flurbiprofen; lidocaine; molecular complex; transdermal.

Grants and funding

This study was supported by Hoshi University Grant-in-Aid for Leading Research Project grants in 2017 and 2018 by the OTC Self-Medication Promotion Foundation 2018 and the Mochida Memorial Foundation for Medical and Pharmaceutical Research 2019–2020 (T.F.).