In vitro release and in vivo absorption in beagle dogs of meloxicam from Eudragit FS 30 D-coated pellets.
The objective of this study was to develop meloxicam-loaded colon-specific pellets coated with Eudragit FS 30 D and further evaluate their in vitro release and in vivo absorption in beagle dogs. Meloxicam-loaded cores (drug loading, 4.8%, w/w) were prepared by layering drug-binder (HPMC)-solubilizer (beta-cyclodextrin) solution onto nonpareils (710-850 microm) and then coated with a copolymer of methyl acrylate, methyl methacrylate and methacrylic acid (Eudragit FS 30 D). The obtained pellets with 15% (w/w) coating level had a spherical form and a smooth surface with coating thickness approximately 28 microm. The in vitro drug release from the pellets was pH-dependent with sufficient gastric resistance (pH 1.2: no release; pH 6.8: 6%; pH 7.0: 52%; pH 7.2: 100%; pH 7.4: 100%, after 3 h incubation). In vivo study was carried out using pentagastrin-pretreated beagle dogs. The onset of meloxicam absorption from the coated pellets with 15% (w/w) Eudragit FS 30 D (3.0+/-0.8 h) was significantly delayed (p<0.05) compared to that from the uncoated drug-layered cores (0.6+/-0.3 h). The area under the meloxicam plasma concentration-time curve (AUC(0-->96)(h) was not significantly different between the two preparations (p>0.05), although AUC(0-->96)(h) obtained after oral administration of coated pellets (142.5+/-59.6 microg h/ml) was lower than that obtained after administration of uncoated drug-layered cores (180.8+/-61.9 microg h/ml). These results suggested that meloxicam could be delivered to the colon with 15% (w/w) coating level of Eudragit FS 30 D and this polymer coating had no significant influence on the relative bioavailability of meloxicam of the pellets.
Gao
Chunsheng
C
Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing 100850, PR China.
Huang
Jian
J
Jiao
Yan
Y
Shan
Li
L
Liu
Yan
Y
Li
Ying
Y
Mei
Xingguo
X
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations; D004285:Dogs; D006863:Hydrogen-Ion Concentration; D065347:Hypromellose Derivatives; D007408:Intestinal Absorption; D008297:Male; D000077239:Meloxicam; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D011109:Polymethacrylic Acids / Q000737:chemistry*; D012995:Solubility; D013843:Thiazines / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics; D013844:Thiazoles / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D011109:Polymethacrylic Acids; D013843:Thiazines; D013844:Thiazoles; C038300:methylmethacrylate-methacrylic acid copolymer; D065347:Hypromellose Derivatives; D008747:Methylcellulose; D000077239:Meloxicam