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

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.

The Development and Characterization of Novel Ionic Liquids Based on Mono- and Dicarboxylates with Meglumine for Drug Solubilizers and Skin Permeation Enhancers

“…FRP, a lipophilic drug previously studied in transdermal systems, was used as the model drug [ 55 , 56 ]. To improve FRP percutaneous absorption through ionic liquidation, we have previously reported that the drug–drug IL of FRP and lidocaine, a local anesthetic, solves the problem of skin permeation [ 57 ]. Although some progress has been made, further research is needed to optimize the use of ILs as skin permeation enhancers for FRP transdermal delivery.…”

Drug complexes: Perspective from Academic Research and Pharmaceutical Market

“…In addition to inclusion complex formation, CDs and drug-CD complexes at higher concentrations can form aggregates in aqueous media, and aggregate formation is proportional to CD and drug-CD complex concentration. These aggregates are formed through non-inclusion complexation or micellar Solvent evaporation method Enhancing solubility and permeability of Flurbiprofen [64] effects. Numerous studies reported that aggregates could also enhance the solubility of lipophilic drugs by acting as drug reservoirs [75].…”

Strategies for Improving Transdermal Administration: New Approaches to Controlled Drug Release

“…Researchers created an amorphous molecular complex by combining different antiinflammatory substances (flurbiprofen, etodolac, naproxen, piroxicam and indomethacin) and lidocaine and examined the physicochemical properties of the complex [44][45][46][47].…”

“…The focus was on intermolecular flurbiprofen-lidocaine interaction. They found that the solubility of flurbiprofen was 100 times higher than the product alone, and the solubility of lidocaine was 2 times higher [46]. The conclusion was that it was possible to develop a transdermal preparation with anti-inflammatory and analgesic effects useful for treating the pain of various diseases [46,47].…”