title: Influence of neutron activation factors on matrix tablets for site specific delivery to the colon.
abstract: The impact of the neutron activation procedure, i.e. incorporation of samarium oxide (Sm(2)O(3)) and neutron irradiation, on the compression properties (including the crushing strength) and in vitro dissolution of potential colonic delivery systems based on matrix tablets of amidated pectin (Am.P) or two types of hydroxypropyl methylcellulose (HPMC) was investigated. The neutron activation factors did not influence the compression properties of the tablets. Replacement of magnesium stearate with samarium stearate in directly compressed Am.P tablets to achieve both radiolabelling and lubrication resulted in a greater extent of concentration-dependent reduction of the crushing strength. Dissolution tests demonstrated that irradiation increased the release of the model drug ropivacaine from the tablets. The extent of this increase was unexpectedly low considering the previously observed degradation of the polymer expressed as an irradiation-induced viscosity reduction in solutions prepared from the polymers. Delayed-release coating with Eudragit L 100 protected the HPMC tablets against the release-increasing effect of irradiation until the late phases of release. Sm(2)O(3) retarded the release to a varying extent depending on particle characteristics. Incorporation of Sm(2)O(3) in the coating layer did not influence the release. However, one-third of the radioactivity leached from the coating within 60 min in 0.1 M HCl.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, University of Oslo, Norway. s.f.ahrabi@farmasi.uio.no
authors.forename: S F
authors.initials: SF
authors.lastname: Ahrabi
authors.forename: J
authors.initials: J
authors.lastname: Heinämäki
authors.forename: S A
authors.initials: SA
authors.lastname: Sande
authors.forename: C
authors.initials: C
authors.lastname: Graffner
mesh_terms: D000577:Amides / Q000008:administration & dosage / Q000493:pharmacokinetics; D000704:Analysis of Variance; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003106:Colon / Q000378:metabolism*; D004339:Drug Compounding; D005079:Excipients; D006244:Hardness / Q000528:radiation effects; D007785:Lactose / Q000031:analogs & derivatives; D008747:Methylcellulose / Q000031:analogs & derivatives; D008855:Microscopy, Electron, Scanning; D009502:Neutrons; D010078:Oxazines; D010368:Pectins; D011109:Polymethacrylic Acids; D000077212:Ropivacaine; D012493:Samarium / Q000008:administration & dosage / Q000493:pharmacokinetics; D012995:Solubility; D013228:Stearates / Q000008:administration & dosage / Q000493:pharmacokinetics; D013607:Tablets / Q000528:radiation effects*
chemical_list: D000577:Amides; D005079:Excipients; D010078:Oxazines; D011109:Polymethacrylic Acids; D013228:Stearates; D013607:Tablets; C038300:methylmethacrylate-methacrylic acid copolymer; D012493:Samarium; D000077212:Ropivacaine; D010368:Pectins; D008747:Methylcellulose; C071191:MK 458; D007785:Lactose