Enhanced Bioavailability and Gastric Protection of the NSAIDs Meloxicam-Cyclodextrin Microparticles

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely prescribed for painful and inflammatory disorders; however, poor bioavailability and gastric ulceration may limit therapeutic outcomes. This study, the first to integrate four cyclodextrins (CDs), gastric safety, bioavailability, and green HPLC validation, aimed to prepare meloxicam (Melo)-CD supramolecular complexes to enhance solubility, dissolution, bioavailability, and reduce ulcerogenic potential following 10-day repeated administration. Native β-CD and three derivatives were complexed with Melo using physical mixing (PM) and coprecipitation (Coppt). The optimized Melo (HP)-β-CD Coppt was compressed into tablets and compared with commercial immediate-release tablets. Complexes were characterized by particle size analysis, solubility, molecular docking, dissolution, differential scanning calorimetry, and Fourier-transform infrared spectroscopy, followed by in vivo gastric safety evaluation in rodents. A rapid, sensitive, eco-friendly, and cost-effective greenness-assisted HPLC method was developed and validated for Melo determination in plasma. Docking suggested inclusion complexation with HP- and hydroxyethyl (HE)-β-CDs. Solubility and dissolution increased by up to 575- and 25-fold, respectively. HEβ-CD complexes provided superior gastric protection without submucosal scarring or fibrosis. HP β-CD complexes significantly enhanced oral Melo bioavailability by over fivefold versus commercial tablets (P < 0.01). These findings highlight CDs as promising solubilizing and safety-enhancing excipients for Melo and potentially other NSAIDs.