Development of Pelubiprofen Tromethamine with Improved Gastrointestinal Safety and Absorption

• Published in: Pharmaceutics Vol. 13; no. 5; p. 745
• Main Authors: Park, Ji Yeon, Oh, Dong Ho, Park, Sang-Wook, Chae, Bo Ram, Kim, Chul Woo, Han, Sang Heon, Shin, Hyeon Jong, Yeom, Soo Bin, Lee, Da Yeong, Park, Min Kyu, Park, Sang-Eun, Park, Jun-Bom, Lee, Kyung-Tae
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 18.05.2021; MDPI
• Subjects: absorption; Arthritis; Bioavailability; gastrointestinal safety; Gene expression; High density polyethylenes; Humidity; pelubiprofen tromethamine; Permeability; solubility; Spectrum analysis; United States > US; Germany
• ISSN: 1999-4923; 1999-4923
• DOI: 10.3390/pharmaceutics13050745

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.