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

Abstract

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) with IBU and NAP, which opens the opportunity for a new delivery mode of these combination drugs. [DPH][IBU] and [DPH][NAP] PILs exhibit low ionicity, as confirmed by Fourier transform infrared and H NMR spectroscopy, and accompanied by low diffusivity, high viscosity, and poor ionic conductivity. Evaluation of pharmaceutical properties of the two PILs showed that these PILs, despite high solubility and good wettability, exhibited low dissolution rates, owing to the poor dispersion of the PIL drops and the resultant small surface area during dissolution. However, when loaded into a mesoporous carrier, the PIL-carrier composites exhibited improved dissolution rates along with excellent flow properties and easy handling. Oral capsules of both PILs were developed using such composites. Such capsule products exhibited acceptable drug release and bioavailability as demonstrated by a predictive artificial stomach-duodenum dissolution test.

Polymerizable Ionic Liquids for Solid-State Polymer Electrolytes

“…Ionic liquids (ILs) possess a wide range of applications, being employed in CO 2 adsorption [1], catalysis [2] or as solvents [3]. They are promising candidates in drug design [4] and drug delivery systems [5] due to their high biological activity [6] and the possibility to combine bioactive cations with bioactive anions, e.g., the salicylate (Sal) ionic liquid (IL) [EMIM-OSal][Sal] [7]. Within the field of energy storage systems, such as lithium ion batteries, ionic liquids are discussed as alternatives to conventional electrolytes [8].…”

Discovery, Characterization, and Pharmaceutical Applications of Two Loratadine–Oxalic Acid Cocrystals

“…The larger red-shift of Lor-Oxa hydrate (26 cm −1 ) than Lor-Oxa CAB (9 cm −1 ) of the C=O peak can be explained by the O-H•••O (2.977 Å) hydrogen bond formation between ester C=O and water. The ≥100 cm −1 red-shift of the C=O absorption band of a fully deprotonated carboxylate group [33] was not obvious in the FT-IR spectra of both Lor-Oxa hydrate and Lor-Oxa CAB because of the overlapping of the much stronger C=O absorption bands of Lor. The low intensity of O-H absorption bands of Oxa in Lor-Oxa CAB is attributed to its participation in strong charge-…”

“…The larger red-shift of Lor-Oxa hydrate (26 cm −1 ) than Lor-Oxa CAB (9 cm −1 ) of the C=O peak can be explained by the O-H•••O (2.977 Å) hydrogen bond formation between ester C=O and water. The ≥100 cm −1 red-shift of the C=O absorption band of a fully deprotonated carboxylate group [33]…”

Mechanism for the Reduced Dissolution of Ritonavir Tablets by Sodium Lauryl Sulfate

“…The ASD apparatus was similar to that previously described. 14,22,23 In brief, it consists of 2 jacketed beakers with temperature controlled at 37 C using a water bath to simulate stomach and duodenum, where the fluid flow is regulated by a programmatically controlled peristaltic pump (Masterflex L/S Easy-Load II pump; Cole-Parmer, Vernon Hills, IL).…”