Improved absorption of meloxicam via salt formation with ethanolamines.
The present study aimed to investigate the effect of ethanolamine salt formation on the dissolution as well as in vivo pharmacokinetics of meloxicam. Three meloxicam-ethanolamine salts were prepared and their in vitro dissolution profiles were examined at pH 1.2 and 6.8. The pharmacokinetic profiles of meloxicam following an oral administration of meloxicam or its ethanolamine salts were also evaluated in rats. The dissolution rates of meloxicam and its ethanolamine salts were similarly slow at pH 1.2, however, at pH 6.8, ethanolamine salt formation significantly enhanced the dissolution rate of meloxicam. Meloxicam diethanolamine salt exhibited the highest dissolution rate at pH 6.8. The faster dissolution of meloxicam via ethanolamine salt formation at pH 6.8 appeared to be correlated well with more rapid absorption of meloxicam in rats. Tmax of meloxicam was significantly (p<0.05) shortened following an oral administration of ethanolamine salts. Furthermore, ethanolamine salts exhibited a trend toward the increase in AUC0-4 (initial exposure), while the overall exposure (AUC0-24) was similar between meloxicam and its salts. In conclusion, the ethanolamine salts of meloxicam, particularly diethanolamine salt of meloxicam, facilitated the rapid absorption of meloxicam while maintaining the prolonged exposure and may be used for the earlier onset of action for meloxicam.
Han
Hyo-Kyung
HK
College of Pharmacy, Chosun University, Dong-gu, Gwangju, Republic of Korea.
Choi
Hoo-Kyun
HK
D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002626:Chemistry, Pharmaceutical; D004983:Ethanolamines / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D006863:Hydrogen-Ion Concentration; D007408:Intestinal Absorption; D008297:Male; D000077239:Meloxicam; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013843:Thiazines / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D013844:Thiazoles / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004983:Ethanolamines; D013843:Thiazines; D013844:Thiazoles; D000077239:Meloxicam