Bioavailability of ibuprofen from hot-melt extruded mini-matrices.
The bioavailability of ibuprofen from hot-melt extruded mini-matrices based on ethyl cellulose and a hydrophilic excipient was tested. During the in vivo evaluation an oral dose of 300 mg ibuprofen was administered to healthy volunteers (n = 9) in a randomized cross-over study and compared with a commercially available sustained release product (Ibu-slow). The plasma samples were analysed by a validated HPLC-UV method. One mini-matrix formulation (F-1) consisted of 30% ibuprofen, 35% ethyl cellulose and 35% hydroxypropyl methylcellulose (Metolose 60 SH 50), while the second formulation (F-2) contained 60% ibuprofen, 20% ethyl cellulose and 20% xanthan gum. These mini-matrices were administered in hard gelatine capsules. Both formulations behaved in vivo as sustained release formulations with an HVD(t50% Cmax) value (time span during which the plasma concentration is at least 50% of the Cmax value) of 7.6 and 12.0 h for formulations F-1 and F-2, respectively, whereas a value of 5.2 h was obtained for Ibu-slow. Although a significantly higher Cmax and AUC(0-24 h) was seen for the reference product, the relative bioavailability of both experimental formulations was about 80%.
De Brabander
Caroline
C
Laboratory of Pharmaceutical Technology, Ghent University, Harelbekestraat 72, 9000 Gent, Belgium.
Vervaet
Chris
C
Van Bortel
Luc
L
Remon
Jean-Paul
JP
D000293:Adolescent; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002214:Capsules; D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005260:Female; D006801:Humans; D065347:Hypromellose Derivatives; D007052:Ibuprofen / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D008875:Middle Aged; D011135:Polysaccharides, Bacterial / Q000737:chemistry; D012995:Solubility
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002214:Capsules; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011135:Polysaccharides, Bacterial; D065347:Hypromellose Derivatives; C013517:ethyl cellulose; D002482:Cellulose; D008747:Methylcellulose; C002563:xanthan gum; D007052:Ibuprofen