title: Solid-state dependent dissolution and oral bioavailability of piroxicam in rats.
abstract: The aim of this study was to gain understanding about the effects of different solid-state forms of a poorly water-soluble piroxicam on drug dissolution and oral bioavailability in rats. Three different solid-state forms of piroxicam were studied: anhydrate I (AH), monohydrate (MH), and amorphous form in solid dispersion (SD). In addition, the effect of a new polymeric excipient Soluplus® (polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer) on oral bioavailability of piroxicam was investigated. Significant differences in the dissolution and oral bioavailability were found between the solid-state forms of piroxicam. Amorphous piroxicam in SD showed the fastest dissolution in vitro and a solid-state transformation to MH in the dissolution medium. Despite the presence of solid-state transformation, SD exhibited the highest rate and extent of oral absorption in rats. Oral bioavailability of other two solid-state forms decreased in the order AH and MH. The use of Soluplus® was found to enhance the dissolution and oral bioavailability of piroxicam in rats. The present study shows the importance of solid-state form selection for oral bioavailability of a poorly water-soluble drug.
authors.affiliation: Department of Pharmacy, Faculty of Medicine, University of Tartu, Nooruse 1, 50411 Tartu, Estonia. andres.lust@ut.ee
authors.forename: Andres
authors.initials: A
authors.lastname: Lust
authors.forename: Ivo
authors.initials: I
authors.lastname: Laidmäe
authors.forename: Mirja
authors.initials: M
authors.lastname: Palo
authors.forename: Andres
authors.initials: A
authors.lastname: Meos
authors.forename: Jaakko
authors.initials: J
authors.lastname: Aaltonen
authors.forename: Peep
authors.initials: P
authors.lastname: Veski
authors.forename: Jyrki
authors.initials: J
authors.lastname: Heinämäki
authors.forename: Karin
authors.initials: K
authors.lastname: Kogermann
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D008297:Male; D010894:Piroxicam / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D033362:Powder Diffraction; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D014961:X-Ray Diffraction
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D010894:Piroxicam