title: Development of meloxicam salts with improved dissolution and pharmacokinetic behaviors in rats with impaired gastric motility.
abstract: OBJECTIVE
  Because of its poor solubility in acidic solution, oral absorption and efficacy of meloxicam (MEL) may be reduced in severe pain patients with impaired gastric motility. The present study aimed to develop salt forms to overcome these drawbacks.
  
  
  METHODS
  Upon MEL salt screening with eight counterions, five MEL salts were obtained. The physicochemical properties of these MEL salts were characterized with a focus on morphology, crystallinity, thermal behavior, dissolution, and chemical/photo-stability. Pharmacokinetic profiling of an orally administered MEL salt was also carried out in both normal rats and rats treated with propantheline for the suppression of gastric motility.
  
  
  RESULTS
  Dissolution behaviors for all obtained MEL salts were markedly better than that of crystalline MEL; in particular, the initial dissolution rate of arginine MEL dihydrate (MEL/Arg) was ca. 14-fold higher than that of crystalline MEL. MEL/Arg was found to be chemically and physically stable. There was ca. 18-fold reduction of AUC(0-4) for orally dosed crystalline MEL (1.0 mg-MEL/kg) in propantheline-treated rats compared with that in normal rats. In contrast, there was only a ca. 3-fold difference in AUC(0-4) between normal and propantheline-treated rats after oral administration of MEL/Arg (1.0 mg-MEL/kg).
  
  
  CONCLUSIONS
  From these findings, MEL/Arg may provide improved oral absorption in severe pain patients.
authors.affiliation: Department of Pharmacokinetics and Pharmacodynamics School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Ochi
authors.forename: Ryo
authors.initials: R
authors.lastname: Inoue
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Yamauchi
authors.forename: Shizuo
authors.initials: S
authors.lastname: Yamada
authors.forename: Satomi
authors.initials: S
authors.lastname: Onoue
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001120:Arginine / Q000737:chemistry; D005769:Gastrointestinal Motility / Q000187:drug effects; D008297:Male; D000077239:Meloxicam; D018727:Muscarinic Antagonists / Q000494:pharmacology; D014677:Pharmaceutical Vehicles / Q000737:chemistry*; D011413:Propantheline / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012492:Salts / Q000737:chemistry*; D012995:Solubility; D013843:Thiazines / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D013844:Thiazoles / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D018727:Muscarinic Antagonists; D014677:Pharmaceutical Vehicles; D012492:Salts; D013843:Thiazines; D013844:Thiazoles; D011413:Propantheline; D001120:Arginine; D000077239:Meloxicam