Powdered self-emulsified lipid formulations of meloxicam as solid dosage forms for oral administration.
The objectives of this study were to prepare a powdered self-emulsified (SEDDS) formulation of meloxicam and to compare its oral bioavailability against commercial Mobic tablets. The SEDDS formulation was prepared by in situ salt formation of meloxicam in a blend of lipid excipients and aqueous tris (hydroxymethyl) aminomethane solution. The liquid SEDDS was subsequently adsorbed on silica powder and was tested for size, flow, and crystal growth. The flowability index of the powdered SEDDS was borderline acceptable. Absence of crystal growth with storage was confirmed by DSC and PXRD studies. Dissolution of meloxicam from the powdered SEDDS was >90% vs. <12% for powdered meloxicam and <80% for the commercial tablets. Stability of the powdered formulations after storage in gelatin and HPMC capsules was also evaluated to study the effect of water migration from the fill into capsule shells. Capsules softened to a different extent as a function of fill material with HPMC capsules showing greater resistance to water migration. Finally, oral bioavailability of the formulations was evaluated in beagle dogs. Powdered meloxicam SEDDS formulation showed a 1.3-fold increase in AUC vs. commercial Mobic® tablets. Overall, this study described a novel SEDDS formulation of meloxicam and outlined a systematic approach to adsorbing and testing the flow and stability behavior of powdered SEDDS formulations.
CIMA, a Cephalon Company , Brooklyn Park, MN.
Vikas
V
Agarwal
Alaadin
A
Alayoubi
Akhtar
A
Siddiqui
Sami
S
Nazzal
D000284:Administration, Oral; D000818:Animals; D017849:Animals, Inbred Strains; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics; D001682:Biological Availability; D002214:Capsules; D055598:Chemical Phenomena; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics; D004285:Dogs; D004339:Drug Compounding; D004355:Drug Stability; D004356:Drug Storage; D004655:Emulsions; D005079:Excipients / Q000737:chemistry*; D008055:Lipids / Q000737:chemistry*; D000077239:Meloxicam; D010316:Particle Size; D011208:Powders; D012822:Silicon Dioxide / Q000737:chemistry; D012995:Solubility; D013843:Thiazines / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics; D013844:Thiazoles / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics; D014325:Tromethamine / Q000737:chemistry
D000894:Anti-Inflammatory Agents, Non-Steroidal; D018501:Antirheumatic Agents; D002214:Capsules; D016861:Cyclooxygenase Inhibitors; D004655:Emulsions; D005079:Excipients; D008055:Lipids; D011208:Powders; D013843:Thiazines; D013844:Thiazoles; D014325:Tromethamine; D012822:Silicon Dioxide; D000077239:Meloxicam