Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8513672 | Journal of Pharmaceutical Sciences | 2018 | 34 Pages |
Abstract
Meloxicam (MEL) shows a slow onset of action in severe pain patients on account of delayed gastric motility. This study aimed to develop an amorphous solid dispersion (ASD) of MEL to achieve rapid oral absorption in severe pain patients. ASD formulations of MEL with hydroxypropylmethylcellulose (ASD-MEL/HPMC) and polyacrylates and polymethacrylates (ASD-MEL/EUD) were prepared and physicochemically characterized. Oral absorption behavior of MEL samples was also clarified in both normal and propantheline (PPT)-pretreated rats with impaired gastric motility. MEL in the formulations was amorphous, and ASD formulations of MEL exhibited high dissolution behavior in acidic solution. After oral administration of crystalline MEL (1 mg-MEL/kg), a 69% reduction in AUC0-4 was observed between normal and PPT-pretreated rats. For orally dosed ASD-MEL/HPMC (1 mg-MEL/kg), there were approximately 9- and 12-fold increases of AUC0-4 in normal and PPT-pretreated rats, respectively, in comparison with crystalline MEL (1 mg-MEL/kg). However, the oral absorption behavior of ASD-MEL/EUD (1 mg-MEL/kg) was low and similar to that of crystalline MEL. The infrared spectroscopic study revealed potent interactions between MEL and EUD, possibly leading to marked attenuation of MEL absorption. This ASD approach might provide rapid oral absorption of MEL in severe pain patients, possibly leading to better clinical outcomes.
Keywords
CmaxNBTtmaxNSAIDESI-MSPPTMELPLMNaPBMrOSXRPDarea under the curve of blood concentration versus time curveEUDHPMCAUCDMSOnitroblue tetrazoliumVIsAmorphousElectrospray Ionization Mass SpectrometryUltravioletsodium phosphate bufferdrug-excipient interactionOral absorptionmaximum concentrationGastrointestinal transitstandard errorGERnonsteroidal anti-inflammatory drugPoorly water-soluble drugsDimethyl sulfoxidetime to maximum concentrationInfraredSEMMeloxicamgastric emptying rateScanning electron microscopyPolarized light microscopyVisible lightHydroxypropylmethylcelluloseX-ray powder diffractionSolid dispersionPropantheline
Related Topics
Health Sciences
Pharmacology, Toxicology and Pharmaceutical Science
Drug Discovery
Authors
Hiroki Suzuki, Keisuke Yakushiji, Saori Matsunaga, Yukinori Yamauchi, Yoshiki Seto, Hideyuki Sato, Satomi Onoue,