Development of Pelubiprofen Tromethamine with Improved Gastrointestinal Safety and Absorption.

Pelubiprofen (PEL), which is a commercialized non-steroidal anti-inflammatory drug (NSAID), is associated with the risk of gastrointestinal (GI) adverse events following long-term exposure and has poor water-soluble properties. Here, a new pelubiprofen tromethamine (PEL-T) with improved solubility, permeability, GI safety, and absorption, compared to PEL, has been developed. The nuclear magnetic resonance spectroscopy (NMR), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FT-IR) results confirmed that the PEL-T was well formed. The powder of PEL-T showed the presence of additional 6H protons at δ 3.66-3.61 in the 1H NMR spectrum, and shifted the sharp endothermic peaks at 129 °C in DSC, and the spectrum of distinct absorption peaks in FT-IR. In addition, compared with PEL, PEL-T showed a significantly improved solubility in various media and an increased permeability coefficient (Kp) in Caco-2 cells. Furthermore, compared to PEL oral administration, PEL-T was found to significantly reduce the damaged area in an acute gastric damage rat model. The pharmacokinetic study of the PEL-T powder showed higher maximum plasma concentration (Cmax) and area under the plasma concentration-time curve from 0 h to the last time point (AUCt) than those of the PEL powder. Taken together, our data suggest that PEL-T is a recommendable candidate with enhanced gastrointestinal safety and better absorption compared with commercial PEL.

Determination and validation of LJ-2698, a potent human A3 adenosine receptor antagonist, in rat plasma by liquid chromatography-tandem mass spectrometry and its application in pharmacokinetic study.

LJ-2698, a highly potent human A3 adenosine receptor antagonist with nucleoside structure, was designed to have a minimal species dependence. For further pre-clinical studies, analytical method for the detection of LJ-2698 in rat plasma was developed by liquid chromatography-tandem mass. Plasma samples were processed by protein precipitation method with acetonitrile, using losartan as the internal standard (IS). Chromatographic separation was carried out using a Kinetex C18 column (100 × 4.6 mm; 100 Å; 2.6 µ) with acetonitrile/water with 0.2% (v/v) formic acid (65:35, v/v) in the isocratic mode at a flow rate of 0.4 mL/min. Mass spectrometric detection in multiple reaction monitoring mode was performed with positive electrospray ionization. The mass transitions of LJ-2698 and IS were m/z 412.3 â†’ 294.1 and m/z 423.1 â†’ 207.2, respectively. The calibration curves were linear in the range 5.00-5000 ng/mL (r 2 ≥ 0.998). The lower limit of quantification was established as 5.00 ng/mL. Within- and between-run precisions were <7.01%, as relative standard deviation; and accuracies were in the range 3.37-3.64%, as relative error. The validated method was successfully applied to its pharmacokinetic evaluation after intravenous and oral administration in rats, and the dose-dependent pharmacokinetic behavior of LJ-2698 was elucidated for the first time.

Development of HPLC Method for the Determination of Buspirone in Rat Plasma Using Fluorescence Detection and Its Application to a Pharmacokinetic Study.

A simple and sensitive analytical method for the quantitative determination of buspirone in rat plasma by HPLC with fluorescence detection was developed and validated using naproxen as an internal standard. A relatively small-volume (150 µL) aliquot of rat plasma sample was prepared by a simple deproteinization procedure using acetonitrile as a precipitating organic solvent. Chromatographic separation was performed using Kinetex® C8 column with an isocratic mobile phase consisting of acetonitrile and 10-mM potassium phosphate buffer (pH 6.0) at a flow rate of 1.0 mL/min. The eluent was monitored by fluorescence detector at a wavelength pair of 237/380 nm (excitation/emission). The linearity was established at 20.0-5000 ng/mL, and the limit of detection was 6.51 ng/mL. The precision (≤14.6%), accuracy (89.2-108%), and stability (89.1-101%) were within acceptable ranges. The newly developed method was successfully applied to intravenous and oral pharmacokinetic studies of buspirone in rats.

Application of montmorillonite in bentonite as a pharmaceutical excipient in drug delivery systems.

Montmorillonite is a multifunctional clay mineral and a major component of bentonite. Montmorillonite has been used in various industrial and pharmaceutical fields due to its unique characteristics, which include swelling and adsorption. The high adsorption capacity of montmorillonite contributes to increase drug entrapment and sustained-release of drugs. Montmorillonite generally sustains drug release in many formulations by strongly adsorbing to the drug. In addition, montmorillonite enhances the dissolution rate and bioavailability of hydrophobic drugs. Moreover, montmorillonite was applied to form composites with other polymer-based delivery systems. Thus, montmorillonite could be applied to formulate diverse drug delivery systems to control and/or improve the pharmaceutical properties of drugs, including solubility, dissolution rate, and absorption. In this review, perspectives of applying montmorillonite as a pharmaceutical excipient in drug delivery systems are discussed.