Improving solubility and pharmacokinetics of meloxicam via multiple-component crystal formation.
Meloxicam is a nonsteroidal anti-inflammatory drug prescribed for rheumatoid arthritis, osteoarthritis, postoperative pain and fever. Meloxicam exhibits low solubility in acidic aqueous media and a slow onset of action in biological subjects. An oral dosage form of meloxicam with enhanced aqueous solubility is desired to enable a faster onset of action and its use for mild-to-medium-level acute pain relief. With this in mind, we examine the solubility and pharmacokinetics of 12 meloxicam cocrystals with carboxylic acids. Dissolution studies of meloxicam and its cocrystals were performed in pH 6.5 phosphate buffer solutions at 37 °C. In addition, pharmacokinetic profiles over four hours were acquired after oral administration of a 10 mg/kg (meloxicam equivalent) solid suspension in rats. The majority of meloxicam cocrystals were found to achieve higher meloxicam concentrations in dissolution media and enhanced oral absorption compared to that of pure meloxicam. All meloxicam cocrystals were converted to meloxicam form I when the slurry reached equilibrium. To better understand how cocrystallization impacts the absorption of meloxicam after oral administration, correlations between the in vitro and in vivo data were explored. The results suggest that the meloxicam cocrystals with a faster dissolution rate would exhibit increased oral absorption and an earlier onset of action.
Thar Pharmaceuticals Inc, 3802 Spectrum Boulevard, Suite 120, Tampa, Florida 33612, United States.
David R
DR
Weyna
Miranda L
ML
Cheney
Ning
N
Shan
Mazen
M
Hanna
Michael J
MJ
Zaworotko
Vasyl
V
Sava
Shijie
S
Song
Juan R
JR
Sanchez-Ramos
D000042:Absorption; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002264:Carboxylic Acids / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003460:Crystallization / Q000379:methods; D006863:Hydrogen-Ion Concentration; D008297:Male; D000077239:Meloxicam; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013843:Thiazines / Q000737:chemistry* / Q000493:pharmacokinetics*; D013844:Thiazoles / Q000737:chemistry* / Q000493:pharmacokinetics*
D002264:Carboxylic Acids; D013843:Thiazines; D013844:Thiazoles; D000077239:Meloxicam