Preparation, Characterization, and Formulation Development of Drug–Drug Protic Ionic Liquids of Diphenhydramine with Ibuprofen and Naproxen

• DOI: 10.1021/acs.molpharmaceut.8b00569
• Publication Date: 2018-07-23T23:06:50Z
• Authors: Chenguang Wang; Sujay A. Chopade; Yiwang Guo; Julia T. Early; Boxin Tang; En Wang; Marc A. Hillmyer; Timothy P. Lodge; Changquan Calvin Sun
• Keywords: Ibuprofen

Diphenhydramine (DPH) has been used with ibuprofen (IBU) or naproxen (NAP) in combined therapies to provide better clinical efficacy as an analgesic and sleep aid. We discovered that DPH can form protic ionic liquids (PILs) IBU NAP, which opens the opportunity for a new delivery mode of these combination drugs. [DPH][IBU] [DPH][NAP] PILs exhibit low ionicity, confirmed by Fourier transform infrared 1H NMR spectroscopy, accompanied diffusivity, high viscosity, poor conductivity. Evaluation pharmaceutical properties two showed PILs, despite solubility good wettability, exhibited dissolution rates, owing dispersion PIL drops resultant small surface area during dissolution. However, when loaded into mesoporous carrier, PIL-carrier composites improved rates along excellent flow easy handling. Oral capsules both were developed using such composites. Such capsule products acceptable drug release bioavailability demonstrated predictive artificial stomach–duodenum test.