title: Mesoporous silica sub-micron spheres as drug dissolution enhancers: Influence of drug and matrix chemistry on functionality and stability.
abstract: Mesoporous silica particles prepared through a simplified Stöber method and low temperature solvent promoted surfactant removal are evaluated as dissolution enhancers for poorly soluble compounds, using a powerful anticancer agent belonging to pyrroloquinolinones as a model for anticancer oral therapy, and anti-inflammatory ibuprofen as a reference compound. Mesoporous powders composed of either pure silica or silica modified with aminopropyl residues are produced. The influence of material composition and drug chemical properties on drug loading capability and dissolution enhancement are studied. The two types of particles display similar size, surface area, porosity, erodibility, drug loading capability and stability. An up to 50% w/w drug loading is reached, showing correlation between drug concentration in adsorption medium and content in the final powder. Upon immersion in simulating body fluids, immediate drug dissolution occurred, allowing acceptor solutions to reach concentrations equal to or greater than drug saturation limits. The matrix composition influenced drug solution maximal concentration, complementing the dissolution enhancement generated by a mesoporous structure. This effect was found to depend on both matrix and drug chemical properties allowing us to hypothesise general prediction behaviour rules.
authors.affiliation: Department of Industrial Engineering and INSTM Padova RU, University of Padova, via Marzolo 9, 35131 Padova, Italy; Micro System Technology RU, Center for Materials and Microsystems, Bruno Kessler Foundation, via Sommarive 18, 38123 Trento, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Brigo
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, University of Padova, via Marzolo 5, 35131, Padova, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Scomparin
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, University of Padova, via Marzolo 5, 35131, Padova, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Galuppo
authors.affiliation: Helmholtz-Zentrum Geesthacht, Institute of Materials Research - Dept. of Nanotechnology, Max-Planck-Strasse 1, D-21502 Geesthacht, Germany.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Capurso
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, University of Padova, via Marzolo 5, 35131, Padova, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Ferlin
authors.affiliation: Department of Physics and Astronomy Galileo Galilei, University of Padova, via Marzolo 8, 35131 Padova, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Bello
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, University of Padova, via Marzolo 5, 35131, Padova, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Realdon
authors.affiliation: Department of Industrial Engineering and INSTM Padova RU, University of Padova, via Marzolo 9, 35131 Padova, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Brusatin
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, University of Padova, via Marzolo 5, 35131, Padova, Italy. Electronic address: margherita.morpurgo@unipd.it.
authors.forename: Margherita
authors.initials: M
authors.lastname: Morpurgo
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D004355:Drug Stability; D008863:Microspheres; D053758:Nanoparticles / Q000737:chemistry*; D044367:Phase Transition; D012822:Silicon Dioxide / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D012822:Silicon Dioxide
keywords: Anticancer oral therapy; Drug dissolution enhancement; Mesoporous materials; Microparticles; Nanoparticles; Sol–gel process