Zaltoprofen

Ionic liquid transdermal penetration enhancers (IL@TPEs) as new enhancement methods have significant advantages in the transdermal drug delivery system. However, the scientific frameworks for the design of efficient IL@TPEs and their applications in transdermal formulations were still lack. So, a series of novel biomimetic phospholipid-inspired IL@TPEs (PIL@TPEs) were designed and synthesized. The developed QSARs proved that enhancement efficacy of PIL@TPEs depended on pKa of drugs and M.W., Polar., and pKa of cations. Surprisingly, the PIL@TPEs dissociated during transdermal process, and skin penetration amounts of acidic drugs was inversely proportional to skin retention amounts of cations, which showed that action modes of PIL@TPEs were different from conventional enhancers. The novel mechanisms of PIL@TPEs were elucidated by quantitative determination of dynamic interaction among cations, anions, drugs, and skins. The PIL@TPEs with high enhancement efficiency owned strong interactions with drugs determined by ATR-FTIR, Raman and NOESY. Moreover, the PIL@TPEs owning better stability in skin ensured the production of strong interactions with lipids and keratins characterized by ATR-FTIR, ¹H NMR and CLSM. The good safety of optimized PIL@TPEs was proved by determining cytotoxicity, apoptosis, inflammatory cells, and cytokines. In conclusion, this project will make an important contribution to the design and application of IL@TPEs.

Deuterated and tritiated analogs of drugs are valuable compounds for pharmaceutical and medicinal chemistry. In this work, we present a novel hydrogen isotope exchange reaction of drugs using non‐directed homogeneous Pd‐catalysis. Aromatic C−H activation is achieved by a commercially available pyridine ligand. Using the most convenient and cheapest deuterium source, D2O, as the only solvent 39 pharmaceuticals were labelled with clean reaction profiles and high deuterium uptakes. Additionally, we describe the first application of non‐directed homogeneous Pd‐catalysis for H/T exchange on three different pharmaceuticals by using T2O as isotopic source, demonstrating the applicability to the synthesis of radiotracers.