期刊
MOLECULAR PHARMACEUTICS
卷 7, 期 1, 页码 227-236出版社
AMER CHEMICAL SOC
DOI: 10.1021/mp900221e
关键词
Poorly soluble drugs; porous silicon; solid state stability; in vitro dissolution; in vivo pharmacokinetics; in vitro-in vivo correlation (IVVC)
资金
- Australian Research Council [LP0562379]
- pSivida Ltd
- Australian Research Council
Surface functionalized mesoporous silicon (pSi) microparticles are reported as a solid dispersion carrier for improving dissolution and enhancing the orally administered pharmacokinetics (fasted rat model) of indomethacin (IMC), employed as a model poorly soluble BCS type 11 drug. IMC was loaded via immersion/solvent evaporation onto the thermally oxidized pSi particles, which provide a stable hydrophilic matrix with a nanoporous structure. The solid state properties of IMC loaded pSi were characterized by Fourier transform infrared spectroscopy, X-ray powder diffraction, differential scanning calorimetry and thermogravametric analysis. IMC molecules are encapsulated in a noncrystalline state due to geometric confinement in the nanopores; stability of the noncrystalline state has been demonstrated for several months under accelerated storage conditions. The pSi carrier facilitates accelerated immediate release of IMC and enhanced oral delivery performance in comparison with crystalline indomethacin and Indocid i.e. a 4-times reduction on T-max, a 200% increase on C-max and a significant increase in bioavailability. The in vitro-in vivo correlation is discussed based on the noncompartment model and gives insight into the delivery mechanism for the pSi carrier.
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