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Development of Pelubiprofen Tromethamine with Improved Gastrointestinal Safety and Absorption
- Source :
- Pharmaceutics, Vol 13, Iss 5, p 745 (2021)
- Publication Year :
- 2021
- Publisher :
- MDPI AG, 2021.
-
Abstract
- 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.
Details
- Language :
- English
- ISSN :
- 13050745 and 19994923
- Volume :
- 13
- Issue :
- 5
- Database :
- Directory of Open Access Journals
- Journal :
- Pharmaceutics
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.34812bcd0e9049e5839c9e4d24240ee5
- Document Type :
- article
- Full Text :
- https://doi.org/10.3390/pharmaceutics13050745