title: Physicochemical stability of high indomethacin payload ordered mesoporous silica MCM-41 and SBA-15 microparticles.
abstract: Stability of high indomethacin (IMC) content formulations based on ordered mesoporous silica MCM-41 and SBA-15 materials was studied before and after a 3 month storage in stressed conditions (30°C/56% RH). Overall, the physical stability of the samples was found satisfactory after the storage. However, some issues with the chemical stability were noted, especially with the MCM-41 based samples. The stability issues were evident from the decreased HPLC loading degrees of the drug after stressing as well as from the observed extra peaks in the HPLC chromatograms of the drug in the stressed samples. Drug release from the mesoporous formulations before stressing was rapid at pH 1.2 in comparison to bulk crystalline IMC. The release profiles also remained similar after stressing. Even faster and close to complete IMC release was achieved when the pH was raised from 1.2 to 6.8. To our knowledge, this is the first report of chemical stability issues of drugs in mesoporous silica drug formulations. The present results encourage further study of the factors affecting the chemical stability of drugs in mesoporous silica MCM-41 and SBA-15 formulations in order to realize their potential in oral drug delivery.
authors.affiliation: University of Helsinki, FI-00014, Finland. tarja.limnell@orionpharma.com
authors.forename: Tarja
authors.initials: T
authors.lastname: Limnell
authors.forename: Teemu
authors.initials: T
authors.lastname: Heikkilä
authors.forename: Hélder A
authors.initials: HA
authors.lastname: Santos
authors.forename: Sanna
authors.initials: S
authors.lastname: Sistonen
authors.forename: Sanna
authors.initials: S
authors.lastname: Hellstén
authors.forename: Timo
authors.initials: T
authors.lastname: Laaksonen
authors.forename: Leena
authors.initials: L
authors.lastname: Peltonen
authors.forename: Narendra
authors.initials: N
authors.lastname: Kumar
authors.forename: Dmitry Yu
authors.initials: DY
authors.lastname: Murzin
authors.forename: Marjatta
authors.initials: M
authors.lastname: Louhi-Kultanen
authors.forename: Jarno
authors.initials: J
authors.lastname: Salonen
authors.forename: Jouni
authors.initials: J
authors.lastname: Hirvonen
authors.forename: Vesa-Pekka
authors.initials: VP
authors.lastname: Lehto
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding / Q000379:methods*; D004355:Drug Stability; D004356:Drug Storage / Q000379:methods; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007213:Indomethacin / Q000737:chemistry*; D010316:Particle Size; D016062:Porosity; D012822:Silicon Dioxide / Q000138:chemical synthesis / Q000737:chemistry*; D012995:Solubility
chemical_list: D004337:Drug Carriers; C509968:MCM-41; C509969:SBA-15; D012822:Silicon Dioxide; D007213:Indomethacin