Non-ordered Mesoporous Silica Research Articles

Study of Disordered Mesoporous Silica Regarding Intrinsic Compound Affinity to the Carrier and Drug-Accessible Surface Area.

There is increasing research interest in using mesoporous silica for the delivery of poorly water-soluble drugs that are stabilized in a noncrystalline form. Most research has been done on ordered silica, whereas far fewer studies have been published on using nonordered mesoporous silica, and little is known about intrinsic drug affinity to the silica surface. The present mechanistic study uses inverse gas chromatography (IGC) to analyze the surface energies of three different commercially available disordered mesoporous silica grades in the gas phase. Using the more drug-like probe molecule octane instead of nitrogen, the concept of a "drug-accessible surface area" is hereby introduced, and the effect on drug monolayer capacity is addressed. In addition, enthalpic interactions of molecules with the silica surface were calculated based on molecular mechanics, and entropic energy contributions of volatiles were estimated considering molecular flexibility. These free energy contributions were used in a regression model, giving a successful comparison with experimental desorption energies from IGC. It is proposed that a simplified model for drugs based only on the enthalpic interactions can provide an affinity ranking to the silica surface. Following this preformulation research on mesoporous silica, future studies may harness the presented concepts to guide formulation scientists.

Low-Field NMR to Characterize the Crystalline State of Ibuprofen Confined in Ordered or Nonordered Mesoporous Silica.

The crystalline state of ibuprofen (IBU) confined in mesoporous silica was characterized using low-field time-domain nuclear magnetic resonance (TD-NMR). IBU was loaded into ordered (Santa Barbara Amorphous-15 [SBA-15]; SBA) or nonordered mesoporous silica (Sylysia 320; SYL) using a well-known incipient wetness impregnation method. The dissolution profile of IBU from the silica was measured. The IBU-loaded SBA showed a relatively higher drug concentration at 10 and 20 min, which was typical of a supersaturated solution. However, it did not maintain that concentration. By contrast, the IBU-loaded SYL did not show such a dissolution profile in the early stage. To characterize the crystalline state of IBU confined in silica, the T1 relaxation time of IBU-loaded silica powder was measured and analyzed by curve fitting. Monophasic T1 relaxation was observed for IBU-loaded SBA. This may indicate that the amorphous phase, which has various molecular mobilities, was close to within the length of 1H spin diffusion. The TD-NMR technique, even if the sample is powder, can rapidly and easily measure NMR relaxation. Therefore, it can be useful toward fully characterizing the crystalline state of drugs confined in mesopores.

Fabrication, In Vitro and In Vivo Evaluation of Non-Ordered Mesoporous Silica-Based Ternary Solid Dispersions for Enhanced Solubility of Flurbiprofen

The aim of this study was to improve the solubility and prevent the ulcerogenic effect of flurbiprofen. Initially, binary and ternary solid dispersions (BSDs and TSDs) of flurbiprofen were prepared by using non-ordered mesoporous silica and gelucire. After preformulation testing (solubility, flow properties, % yield, and entrapment efficiency), four formulations were selected for further detailed studies. Solid-state characterization of optimized formulations (S1, S6, S7, and S12) showed successful drug incorporation in the solid dispersion at the molecular state without any noticeable interactions. The in vitro solubility and release study showed an increase in solubility and 98–100% of drug release in 30–45 min. The in vivo gastro-protective effect of the optimized formulations containing flurbiprofen and silica (1:1) with 25% w/w gelucire (S6 and S12) showed a reduction in the gastric lesion index (GLI) after four days of treatment. Moreover, histological images of the stomach lining (S6 and S12) illustrated normal epithelial cells and a partially protected mucosal membrane. Thus, TSD exhibited a significant increase in solubility and the dissolution rate and reduced the gastric ulceration. Therefore, TSDs are dubbed as efficacious carriers to enhance the bioavailability of flurbiprofen while simultaneously reducing its side effects.

Mesoporous silica supported phosphotungstic acid catalyst for glycerol dehydration to acrolein

Conversion of glycerol to acrolein is a useful reaction for value-added application of biodiesel-derived glycerol and bioenergy development. The high-performance solid acid catalyst is essential to this dehydration reaction. In this paper, tungsten-based heteropolyacids (HPA) were supported on non-ordered mesoporous silica (MSU-x) to increase their dispersion and used as catalysts for glycerol dehydration to acrolein. Aiming to reveal the surface structure of HPA and resulting acidic properties, as well as the relationship between acidic properties and dehydration activity, different loadings of H3PW12O40 were supported on MSU-x (10–50 wt%) and the catalysts were characterized by X-ray diffraction (XRD), BET, SEM/TEM, UV–vis diffuse reflectance spectra (DRS), Raman and FT-IR techniques. Their acidic properties were studied by NH3-Temperature Programmed Desorption (NH3-TPD) and Pyridine adsorption methods. The molecular structure and dispersion of H3PW12O40 supported on the catalysts was revealed. The Keggin unit preserved well but with different hydration level for various loadings. The total acid concentration and respective Brønsted/Lewis acid identification were calculated. The acrolein yield increased with H3PW12O40 loading until 30 wt% and showed less change with higher loadings. Based on the correlation of acrolein formation rate with acidic properties, the active role of Brønsted acid and the cooperative role of Brønsted/Lewis acid sites for glycerol dehydration to acrolein were discussed. This work provides new insight into the structure evolution of heteropolyacids and the catalyst design for the glycerol to acrolein.

Monitoring the recrystallisation of amorphous xylitol using Raman spectroscopy and wide-angle X-ray scattering

In this paper we present a fast model system for monitoring the recrystallization of quench-cooled amorphous xylitol using Raman spectroscopy and wide-angle X-ray scattering. The use of these two methods enables comparison between surface and bulk crystallization. Non-ordered mesoporous silica micro-particles were added to the system in order to alter the rate of crystallization of the amorphous xylitol. Raman measurements showed that adding silica to the system increased the rate of surface crystallization, while X-ray measurements showed that the rate of bulk crystallization decreased. Using this model system it is possible to measure fast changes, which occur in minutes or within a few hours. Raman-spectroscopy and wide-angle X-ray scattering were found to be complementary techniques when assessing surface and bulk crystallization of amorphous xylitol.

Grafted non-ordered niobium-silica materials: Versatile catalysts for the selective epoxidation of various unsaturated fine chemicals

Two kinds of niobium(V)-silica catalysts for the selective epoxidation were synthesised by post-synthesis modification of non-ordered mesoporous silica supports, starting from niobocene dichloride via solvent-less organometallic precursor dry impregnation or conventional liquid-phase grafting technique. Grafted Nb/SiO2 solids were used as catalysts, in the presence of aqueous H2O2, for the epoxidation of unsaturated cyclic and terpenic compounds of interest for fine and specialty chemistry, in particular: cyclohexene, 1-methylcyclohexene, limonene, carveol, α-terpineol, isopulegol, carvotanacetol, carvone, as well as squalene and isopulegyl acetate. These catalysts showed high yields (up to 73%) and excellent chemoselectivities to the desired epoxides (up to 98%), also in short reaction times (down to 1h).

Electroactive Properties of 1-propyl-3-methylimidazolium Ionic Liquid Covalently Bonded on Mesoporous Silica Surface: Development of an Electrochemical Sensor Probed for NADH, Dopamine and Uric Acid Detection

A hybrid organic-inorganic porous material was successfully prepared through chemical modification of a non-ordered mesoporous silica, obtained by the sol-gel process, with 1-propyl-3-methylimidazolium groups. The porous material was evaluated as a platform for the development of electrochemical sensors, here probed toward the electrooxidation of NADH (β-nicotinamide adenine dinucleotide), uric acid (UA) and dopamine (DA). The presence of cationic imidazolium groups on the surface of the hybrid silica-based material allowed the electrochemical detection of these biomolecules without any other electron mediator or biomolecular recognition component. Such behavior highlights the potentiality of this material to be applied in the development of new electrochemical sensing devices. Theoretical calculations based on density functional theory emphasizes that the cationic character of imidazolium group provides better oxidation conditions if the solvent effect is minimized.

Use of titanium-containing silica catalysts prepared by rapid and straightforward method in selective oxidations

A series of titanium-containing silica catalysts (Ti4/SiO2) with small oligomeric Ti centres is obtained by impregnation of the air-stable and water-soluble tetranuclear Ti complex (NH4)8[Ti4(C6H4O7)4(O2)4]·8H2O onto commercial non-ordered mesoporous silica supports. Catalyst preparation is performed under very mild conditions, with no controlled atmosphere, following a simple, cheap, safe and sustainable methodology. Ti4/SiO2 catalysts can be used in the presence of TBHP or aqueous hydrogen peroxide and were tested in the selective oxidation of limonene, cyclohexene, trans-stilbene and 2,3,6-trimethylphenol. These catalysts showed performances fully comparable to (or even better than) those obtained with titanium-silicate materials prepared via conventional post-synthesis grafting approaches from organometallic precursors.

Deactivation mechanism of Pd supported on ordered and non-ordered mesoporous silica in the direct H 2O 2 synthesis using CO 2-expanded methanol

The deactivation mechanism of Pd supported on silica and mesoporous silica (SBA-15) using CO 2-expanded methanol as solvent was studied in the direct synthesis of H 2O 2 in batch and semi-continuous batch reactor tests as well as its hydrogenolysis. Fresh and used catalysts were characterized by TPR and CO chemisorption. The results evidence the presence of deactivation, which can be correlated to the loss of accessible active metal surface area due to sintering of Pd, but there is also an effect of the presence of the ordered mesoporous structure and of the reaction conditions. The higher concentration of H 2 in solution in semi-continuous batch reactor tests with respect to batch reactor tests leads to a more relevant deactivation in Pd-SiO 2 with respect to Pd-SBA-15, but a higher initial activity, due to the fact that H 2 accelerates the reduction of the Pd species which are less reducible in Pd-SiO 2 than in Pd-SBA-15. Pd-SBA-15 shows a higher H 2O 2 selectivity and productivity with respect to Pd-SiO 2 in batch reactor tests, related to the presence of easier reducible Pd species. Another difference is related to the different mechanism of sintering. On the SBA-15 support, due to the presence of the ordered mesoporosity, the Pd particles migrate into the SBA-15 channels forming elongated 1D-type particles. In Pd-SiO 2 catalyst, instead, the sintering of the Pd particles leads to large aggregates of Pd particles in the range of 20–25 nm.

Drug Delivery Formulations of Ordered and Nonordered Mesoporous Silica: Comparison of Three Drug Loading Methods

A poorly soluble model drug, indomethacin (IMC), was loaded into two types of silica particles using three different loading methods. The loading efficiency and the extent/rate of drug release were evaluated. Widely used equipment in pharmaceutical laboratories, rotavapor and fluid bed, were used in the loading. The porous materials used were ordered mesoporous silica MCM-41 and nonordered silica gel Syloid 244 FP EU. The materials differ both in their pore properties and particle sizes. Tablets were successfully compressed from the IMC-loaded particles. Mechanical stability of the porous structures was studied with XRPD and nitrogen sorption after tableting and drug release was evaluated at pH 5.5 before and after tableting. The release of the poorly soluble IMC was faster from the Syloid than from the MCM-41, presumably due to the larger pore size and smaller particle size. Loading of IMC into the MCM-41 microparticles improved the drug dissolution, and blending the microparticles with pharmaceutical excipients improved the IMC release even further. The fast release was also maintained after tableting. Loading of IMC into the Syloid particles alone was sufficient to produce similar IMC release profiles, as in the case of MCM-41 with the excipients.

Comparison of mesoporous silicon and non-ordered mesoporous silica materials as drug carriers for itraconazole

Mesoporous materials have an ability to enhance dissolution properties of poorly soluble drugs. In this study, different mesoporous silicon (thermally oxidized and thermally carbonized) and non-ordered mesoporous silica (Syloid AL-1 and 244) microparticles were compared as drug carriers for a hydrophobic drug, itraconazole (ITZ). Different surface chemistries pore volumes, surface areas, and particle sizes were selected to evaluate the structural effect of the particles on the drug loading degree and on the dissolution behavior of the drug at pH 1.2. The results showed that the loaded ITZ was apparently in amorphous form, and that the loading process did not change the chemical structure/morphology of the particles’ surface. Incorporation of ITZ in both microparticles enhanced the solubility and dissolution rate of the drug, compared to the pure crystalline drug. Importantly, the physicochemical properties of the particles and the loading procedure were shown to have an effect on the drug loading efficiency and drug release kinetics. After storage under stressed conditions (3 months at 40 °C and 70% RH), the loaded silica gel particles showed practically similar dissolution profiles as before the storage. This was not the case with the loaded mesoporous silicon particles due to the almost complete chemical degradation of ITZ after storage.

Surface functionalization of SBA-15 and a nonordered mesoporous silica with a 1,4-diazabicyclo[2.2.2]octane derivative: Study of CuCl 2 adsorption from ethanol solution

This work describes the preparation and characterization of postfunctionalized ordered (SBA-15) and nonordered (SMD) mesoporous silicas with n-propyl-1,4-diazoniabicycle[2.2.2]octane chloride (DbCl) moiety. The main interest is based on the fact that these materials are excellent adsorbents due to the ability of functional groups to retain copper chlorides on their surfaces as anionic complexes CuCl 2 + n n - . The specific surface areas ( S BET) and average pore diameters ( d pore) for SBA-15 and SMD are SBA-15, S BET = 944 m 2 g −1, d pore = 9.0 nm; SMD, S BET = 710 m 2 g −1, d pore = 11 nm. On functionalization with DbCl, reductions in the specific surface areas of the resulting materials (SBA-15/DbCl and SMD/DbCl) are observed and the following functionalization degrees ( ϕ) were determined: SBA-15/DbCl, S BET = 247 m 2 g −1, ϕ = 0.95 mmol g −1; SMD/DbCl, S BET = 83 m 2 g −1, ϕ = 1.2 mmol g −1. The adsorption equilibria of CuCl 2 in ethanol were characterized, and the heterogeneous stability constants, β 1 and β 2, corresponding to formation of CuCl 4 2 - and CuCl 3 - anionic species adsorbed on the surface were found. Also, the effective sorption capacities ( t Q ) were determined: SBA-15/DbCl, log β 1 = 4.46, log β 2 = 7.10, t Q = 0.80 mmol g −1; SMD/DbCl, log β 1 = 4.95, log β 2 = 7.52, t Q = 0.75 mmol g −1. Regeneration of the adsorbents requires a very simple procedure consisting of their immersion in aqueous solution followed by immediate release to the solution phase of the Cu ( OH 2 ) n 2 + species, followed by chloride anions as the counterions.

Tailoring the Hydrophobic Character of Mesoporous Silica by Silylation for VOC Removal

MCM-41 and non-ordered mesoporous silica were modified using hexamethyl-disilazane (HMDS). The hydrophobic and hydrophilic properties of grafted materials were studied and compared to a purely all silica BEA zeolite by using competitive and noncompetitive water toluene adsorption. A linear correlation between the silylation degree and the hydrophobicity measurements has been found for MCM-41 materials. Even if highly silylated MCM-41 material have more hydrophilic sites (silanol groups) than all silica zeolite, water molecule condensation is not observed because these sites are isolated. Thus, the highly silylated MCM-41 sample exhibits not only hydrophobicity 2.3 times higher than all silica BEA zeolite but also possesses a storage capacity for toluene and chlorobenzene 3 times higher than this zeolite. In competition with water, the organic molecule (toluene or chlorobenzene) adsorption is always favored even if water adsorption is enhanced by chlorobenzene polarity.

Assessment of Fe 2O 3/SiO 2 catalysts for the continuous treatment of phenol aqueous solutions in a fixed bed reactor

Different iron-containing catalysts have been tested for the oxidation of phenol aqueous solutions in a catalytic fixed bed reactor in the presence of hydrogen peroxide. All the catalysts consist of iron oxide, mainly crystalline hematite particles, over different silica supports (mesostructured SBA-15 silica and non-ordered mesoporous silica). The immobilization of iron species over different silica supports was addressed by direct incorporation of metal during the synthesis or post-synthesis impregnation. The synthesis conditions were tuned up to yield agglomerated catalysts with iron loadings between 10 and 15 wt.%. The influence of the preparation method and the type of silica support was evaluated in a catalytic fixed bed reactor for the continuous oxidation of phenol in terms of catalysts activity (phenol and total organic carbon degradation) as well as their stability (catalyst deactivation by iron leaching). Those catalysts prepared by direct synthesis, either in presence of a structure-directing agent (Fe 2O 3/SBA-15(DS)) or in absence (Fe 2O 3/SiO 2(DS)), achieved high catalytic performances (TOC reduction of 65% and 52%, respectively) with remarkable low iron leaching in comparison with their silica-based iron counterparts prepared by impregnation. Catalytic results have demonstrated that the synthesis method plays a crucial role in the dispersion and stability of active species and hence resulting in superior catalytic performances.

Highly efficient catalysts for the hydrogenation of nitro-substituted aromatics

Nanoparticles of Co and NiPd, derived from colloidal precursors and supported on commercially available non-ordered mesoporous silica, are highly effective, cheap, recyclable and industrially viable catalysts for the hydrogenation of a range of nitro-substituted aromatics under mild conditions.

A fluoride-catalyzed sol–gel route to catalytically active non-ordered mesoporous silica materials in the absence of surfactants

A fluoride catalyzed route for the synthesis of catalytically active non-ordered mesoporous silica based materials in the absence of surfactants is presented and discussed. This synthesis procedure has allowed the introduction of different organic and inorganic functionalities with specific chemical activities within silica networks with well-tailored mesoporous distributions. Particularly, this sol–gel synthesis route has permitted the synthesis of Al- and Ti-containing mesoporous silica materials that have been found to be catalytically active for acid and redox processes, respectively. This synthetic approach has also allowed the preparation of hybrid organic–inorganic mesoporous materials.