Aqueous re-dispersibility characterization of spray-dried hollow spherical silica nano-aggregates

Hollow spherical aggregates of biocompatible silica nanoparticles are produced by the spray drying technique to facilitate the delivery of the nanoparticles to the lung for potential drug delivery applications. The large geometric size (d_G > 5 µm) and the low density (ρ_eff ≈ 0.3 g/cm³) of the nano-aggregates are specifically formulated to achieve high aerosolization efficiency and an effective lung deposition. The nano-aggregates must readily re-disperse into the primary nanoparticles in an aqueous medium for the nanoparticles to perform their intended therapeutic functions. An aqueous re-dispersibility characterization technique based on the turbidity level measurement is developed for this purpose. A water-soluble excipient (i.e. mannitol), which forms “excipient bridges” interconnecting the nanoparticles, is included in the spray-drying formulation to produce readily re-dispersible nano-aggregates. The nano-aggregate aqueous re-dispersibility depends on (1) the silica: mannitol concentration ratio and (2) the degree of hollowness, where nano-aggregates with a higher shell thickness to particle radius ratio exhibit weaker re-dispersibility due to the poor particle wetting. The spray-drying condition and the silica: mannitol ratio, which lead to the production of highly re-dispersible nano-aggregates having the desired morphology, are determined. The promising results signify the potential application of hollow spherical silica nano-aggregates as an inhaled drug delivery vehicle.     

响应面法优化中空介孔二氧化硅球包载吲哚美辛的工艺研究

采用硬模板法在室温下、中性水溶液中合成了中空介孔二氧化硅球,中空部分直径为250nm,外壳厚度25nm。利用氮气吸附-解吸附、透射电子显微镜、傅里叶变换红外光谱表征了微球的物理化学性质。该微球球形度良好,BET结果显示其比表面积为730.0m²/g,平均孔容1.084cm³/g ,平均孔道直径6.58nm。利用中空介孔二氧化硅球较好的载药性能负载吲哚美辛,并采用三因素的Box-Behnke实验设计对药物负载处方工艺进行优化研究。当IMC/HMSNs质量比为22:1,超声1.4h,震荡吸附23h时实验条件达到最佳,包封率理论值为85.2%。在此条件进行验证实验,吲哚美辛的包封率可达理论预测值的98.7%,说明将 Box-Behnken 实验设计法用于中空介孔二氧化硅球包载吲哚美辛的优化筛选是可行的,且得到的实验观察值与数学模型的预测值相符合。     

Improvement of hollow mesoporous silica nanoparticles synthesis by hard-templating method via CTAB surfactant

In this study, hollow mesoporous silicate nanoparticles using TEOS precursors in the presence of polystyrene template were synthesized. The process was performed in an alcohol-based chemical system and the addition of CTAB surfactant. The polystyrene template was used under controlled conditions having a spherical morphology with a uniform distribution and an average size of 50 nm. The results of the FTIR analysis showed that TEOS pre-cursor particles formed surface boundaries during the synthesis with CTAB surfactants, and also the presence of SiOSi bonds (in the 600 to 1320 cm⁻¹ range) indicates the formation of silicate chains on Polystyrene templates. Thermal analysis studies showed that by using appropriate thermal treatment and precise control, organic compounds can be removed from the system and synthesize hollow mesoporous silicate particles with minimum structural defects at 280 °C. The BET analysis showed that the specific surface area of these particles is 1180 m² g⁻¹. X-ray diffraction results demonstrated that the resulting product was amorphous silica and unwanted phases were not formed in this system. The dynamic light scattering analysis illustrated that the synthesized particles had dimensions ranging from 1 to 10 nm, and the particle size distribution occurred within a narrow range. Scanning electron microscopy images confirm the nodularity of nanoparticles with a mean size of 25–30 nm. Finally, the transmitted electron microscope images showed that the synthesized silicate particles were hollow, so that the diameter of the hollow chamber and its total diameter were about 30 and 80 nm, respectively.     

Effects of polyethylenimine on the dispersibility of hollow silica nanoparticles

In this study, two different methods were applied to disperse hollow silica nanoparticles (HSNP); one employed polyethylenimine (PEI) as the dispersant during the synthesis processes for preparing HSNP, while the other added PEI into suspensions of the prepared HSNP and used milling treatment to achieve the desired dispersion. It was found that adding PEI during the synthesis process of HSNP had no noticeable improvement in the dispersion, while adding PEI into suspensions of the prepared HSNP and utilizing milling treatment resulted in remarkable dispersion improvement. Therefore, the latter was chosen as the method in dispersing HSNP suspensions. The adsorption of PEI on the surface of HSNP and the stability of the aqueous suspensions was investigated. The results indicated that the adsorption of PEI on the surface of HSNP would increase the repulsive energy among particles, hence reducing the agglomeration of HSNP and improving the stability of the aqueous suspensions. The change of HSNP’s ζ potential after adding PEI and the relationship between the adsorbed amount of PEI and pH were also investigated. Translated from Journal of Chemical Engineering of Chinese Universities, 2006, 20(5): 752–758 [译自: 高校化学工程学报]     

The properties of silica aerogels hybridized with SiO2 nanoparticles by ambient pressure drying

In this study, we report the chemical characteristics of silica aerogels that were produced by adding SiO₂ nanoparticles into silica aerogel by ambient pressure drying. We synthesized silica aerogel composites with different weight percentages of SiO₂ nanoparticles ranging from 0 wt% to 0.025 wt% of the total amount of solution. As the wt% of SiO₂ nanoparticles increased, the number of chemical bonds that formed during condensation of the silica aerogel increased because of the presence of surface hydroxyl groups, thus the particle size of the silica aerogels increased. Silica nanoparticle-doping of silica aerogels can be used to control the synthesis of nanocomplex structures.     

Template-free synthesis of uniform hollow silica nanoparticles for controllable antireflection coatings

Antireflection coatings consisting of nanoparticles have promising applications in a wide range of UV optical fields, such as high-power laser systems and space telescopes. However, an open question for these coatings is how to minimize light scattering caused by the nanoparticles. Here, we utilize hollow silica nanoparticles to realize antireflection coatings, which largely diminish light scattering and, hence, exhibit excellent transmission even at UV wavelengths. The hollow silica nanoparticles were synthesized using a template-free approach and then dip coated onto fused silica substrates to form antireflection coatings. The coatings were found to exhibit nearly 100% transmission at any wavelength ranging from the UV to IR bands by variation of the coating thickness. Moreover, the coatings showed relatively high environmental stability because their hollow structures were insensitive to contaminants. This study provides a novel route to fabricate UV antireflection coatings with improved optical properties and good environmental stability, which will help promote the understanding, design and fabrication of optical coatings.     

Spray drying of TiO2 nanoparticles into redispersible granules

We have demonstrated how titania nanoparticles can be spray-dried to produce redispersible granules. The evaluation of different dispersants using rheology, particle size and electrokinetic measurements showed that an anionic carboxylated polyelectrolyte, Dispex N40, was able to stabilize the primary aggregates of the titania nanoparticles with a size of about 180 nm at an addition of 2.4% dry-weight basis over a relatively large pH-range. Transmission electron microscopy showed that the commercial P-25 titania nanopowder could not be deagglomerated down to the individual crystallite size of 15-40 nm. Spherical granules with a size between 20 and 50 μm and a minimum amount of dusty fines could be produced by spray drying the aqueous titania dispersions in a configuration with internal bag filters. The granules could be completely disintegrated and redispersed in water by ultrasonication into a stable suspension with a size distribution that is identical to the as-received powder. The possibility to prepare redispersible nanoparticle granules by spray drying is a route to minimize the risk of airborne exposure and facilitate the handling of nanopowders.     

气溶胶辅助自组装制备中空球形二氧化硅材料的机理及应用

以正硅酸乙酯（TEOS）和甲基三乙氧基硅烷（MTES）为混合硅源,不同配比条件下采用气溶胶辅助自组装技术制备高比表面积的中空介孔二氧化硅纳米颗粒（HMSNs）,并应用于原花青素（PC）的负载,以期提高其生物利用度。利用扫描电镜（SEM）、透射电镜（TEM）、X射线衍射（XRD）、红外图谱（FTIR）和粒径分析（DLS）等对载体颗粒的形成过程、结构特性以及负载性能进行探究,基于BET分析方法计算HMSNs的比表面积,并对孔径分布进行分析。结果表明,前体溶液水解的活性中间体缩合形成二氧化硅网络结构,同时雾化后的气溶胶液滴在径向浓度梯度自组装成球形结构,水解-缩合与自组装过程协同作用促进了分散性良好的介孔二氧化硅（MSNs）的形成。经退火处理、纯化操作去除模板剂NaCl和表面活性剂十六烷基三甲基溴化铵（CTAB）,最终获得具有中空结构的HMSNs。当TEOS/MTES的摩尔比为60/40时,HMSNs具有极大的比表面积（1083m²/g）和较大的孔容积（0.37cm³/g）,其孔径主要分布在2~4nm之间,PC在HMSNs上的负载量可达30.7mg/g。     

Preparation of cubic and spherical hollow silica structures by polystyrene-poly diallyldimethylammonium chloride and polystyrene-poly ethyleneimine hard templates

In this study, hollow silica structures were synthesized by sol-gel/template technique using two types of hard templates: polystyrene-poly diallyldimethylammonium chloride (PS@PDADMAC) and polystyrene-polyethyleneimine (PS@PEI). The obtained templates were evaluated by zeta potential analysis, FTIR, SEM and EDX techniques. The obtained structures were then assessed by the TEM method. By controlling the ratio of the precursors, two morphologies were obtained: hollow spherical and hollow cubic. The results indicated the successful synthesis of two types of hollow silica spheres with the approximated diameters of 63 and 19 nm as well as two types of hollow cubic silica with approximated dimensions of 830 and 58 nm. SEM, XRD, and BET were used to further study morphology, phase composition, and porosity of the hollow silica spheres prepared by PS@PEI templates.     

Iterative model-based experimental design for spherical agglomeration processes

Spherical agglomeration (SA) is a process intensification strategy, which can reduce the number of unit operations in pharmaceutical manufacturing. SA merges drug substance crystallization with drug product wet granulation, reducing capital, and operating costs. However, SA is a highly nonlinear process, thus for its efficient operation model-based design and control strategies are beneficial. These require the development of a high-fidelity process model with appropriately estimated parameters. There are two major problems associated with the development of a high-fidelity process models—(i) selection of the appropriate model corresponding to the underlying process mechanisms, and (ii) accurate estimation of the parameters. This work focuses on the identification of the best fitting model that correlates with experimental observations using cross-validation experiments. Further, an iterative model-based experimental design strategy is developed, which uses D-optimal experimental design criterion to minimize the number of experiments necessary to obtain accurate parameter estimates.     

Synthesis of spherical mesoporous silica nanoparticles with nanometer-size controllable pores and outer diameters

Spherical mesoporous silica particles with tunable pore size and tunable outer particle diameter in the nanometer range were successfully prepared in a water/oil phase using organic templates method. This method involves the simultaneous hydrolytic condensation of tetraorthosilicate to form silica and polymerization of styrene into polystyrene. An amino acid catalyst, octane hydrophobic-supporting reaction component, and cetyltrimethylammonium bromide surfactant were used in the preparation process. The final step in the method involved removal of the organic components by calcinations, yielding the mesoporous silica particles. Interestingly, unlike common mesoporous materials, the particle with controllable pore size (4–15 nm) and particle diameter (20–80 nm) were produced using the method described herein. The ability to control pore size was drastically altered by the styrene concentration. The outer diameter was mostly controlled by varying the concentration of the hydrophobic molecules. Relatively large organic molecules (i.e. Rhodamine B) were well-absorbed in the prepared sample. Furthermore, the prepared mesoporous silica particles may be used efficiently in various applications, including electronic devices, sensors, pharmaceuticals, and environmentally sensitive pursuits, due to its excellent adsorption properties.     

聚合氯化铝的喷雾干燥

介绍了聚合氯化铝的离心喷雾干燥工艺，以及干燥过程中工艺控制的实际问题、节能降耗的实际措施。     

Preparation of hollow spherical articles

A novel method for making hollow articles in spherical and other shapes is outlined. These spheres are prepared by dissolving a film-forming polymer in a sublimable core solvent, shaping the blend while molten, cooling to solidify, and subsequently removing the solid core material as a vapour. The film-forming solid migrates to form a shell having the original core shape and a honeycomb-like porous wall. Inorganic hollow objects can also be made by introducing sinterable solids to the hot solution, subsequently heating to remove the organic portion and further heating to effect sintering. Size, strength, wall thickness, bulk density and surface characteristics can be controlled to suit the end use.     

Application of experimental design to the formulation of glucose oxidase encapsulation by liposomes

Fractional factorial screening design and response surface methodology were applied to optimize the entrapment of glucose oxidase in liposomes by the dehydration–rehydration vesicle (DRV) method. Phosphatidylcholine from different sources, cholesterol:phosphatidylcholine (Ch:PC) and enzyme:lipid (E:L) ratios, buffer pH, sonication frequency and trehalose concentration were the parameters selected for this study. The type of phosphatidylcholine was found to be the most important factor followed by the trehalose concentration, Ch:PC ratio, sonication frequency and E:L ratio. The pH did not play an important role in the response. By treating liposomes with trehalose, as cryoprotectant, the activity of entrapped enzyme decreased by 16%. Two of the factors (cholesterol:phosphatidylcholine and enzyme:lipid ratios) were further studied in a 3² central composite design. The optimized liposomal formulation with an entrapment efficiency of 24% was obtained for egg yolk PC with Ch:PC and E:L ratios of 0.95 and 14.69, respectively, at pH 6 and applying a sonication frequency of 150 W. Copyright © 2004 Society of Chemical Industry     

New composites of spherical bridged polysilsesquioxanes and aggregates of Pd nanoparticles with POSS via ionic interactions

Spherical bridged polysilsesquioxane (BPS) particles with sulfonic groups (BPS–SO₃ ^?) were prepared by the subsequent reduction and oxidation of BPS with disulfide groups (BPS–S–S) after the hydrolysis and condensation reaction of silane monomers with disulfide groups under ammonia and alcoholic solutions. Spherical aggregates of Pd nanoparticles (Pd–polyhedral oligomeric silsesquioxanes, Pd–POSS) were produced by the mixing of POSS and palladium (II) acetate in methanol solution. The average size of BPS–SO₃ ^? and Pd–POSS was about 200–400 and 30–50 nm, respectively. New BPS–SO₃ ^?/Pd–POSS composites with the shape of BPS–SO₃ ^? covered with Pd–POSS nanoparticles were fabricated by ionic interactions between negatively charged BPS–SO₃ ^? and positively charged Pd–POSS. Pd–POSS nanoparticles were more effectively attached to BPS–SO₃ ^? than BPS–S–S, which resulted from the difference of zeta potential between BPS–SO₃ ^? and BPS–S–S. That is, ionic interactions in BPS–SO₃ ^?/Pd–POSS composites were stronger than those in BPS–S–S/Pd–POSS composites. As the storage time was increased, the precipitation of BPS–SO₃ ^?/Pd–POSS composites in methanol solution resulted from the strong complex between BPS–SO₃ ^? and Pd–POSS unlike BPS–S–S/Pd–POSS composites. New particle composites were characterized by Fourier transform infrared spectra, scanning electron microscopy, transmission electron microscopy, and energy dispersive X-ray spectroscopy.     

Spray drying of low-Tg acrylic dispersions

Conclusions  The application of the sequential polymerization technique for the synthesis of structured acrylic latices offers a very interesting way for the spray drying of low Tg polymers. Polymer particles having a soft nucleus and a hard shell can be dried without difficulty and give rise to non-tacky powders. Polymers with the same chemical composition, but with a homogeneous structure are not easily converted into powders. The laboratory spray drying apparatus with a static nozzle produces very fine monodisperse powders, having moderate flowability. Small additions to the crude powders of fluidizing agents, such as micronized silica, significantly improve their flowability. Work carried out at LARAC SpA — ?MW Gruppe, Corso Sempione 13, 21053 Castellanza (VA), Italy     

Subcritical drying of silica gels

Silica aerogel is a sol-gel prepared material characterized by high porosity and large inner surface area. Aerogels can be prepared with a high transparency and low thermal conductivity, giving a material excellent for application as transparent thermal insulator. The traditional route to prepare silica aerogels is by formation of an alcogel by hydrolysis and condensation of silicon alkoxides followed by supercritical drying in an autoclave at high pressure (–100 atm). Unfortunately, this process is expensive and might be dangerous, so drying methods have been developed that operate under ambient conditions. In previous work, we have shown that gels can be strengthened and stiffened by providing new monomers to the alcogel giving xerogels with similar properties as aerogels by drying at ambient pressure (porosity up to 90%). This method of obtaining ambient pressure dried aerogels will be described and special emphasis will be given on the effect of the initial gel structure on the preparation of the xerogels.     

Optimal experimental design for optimal process design: A trilevel optimization formulation

Typical optimal experimental design (OED) methods aim at minimizing the covariance matrix of the estimated parameters regardless of the intended application of the model that is being estimated. This can unnecessarily increase the experimental costs. Herein, we propose a new OED method, which tailors the designed experiments to the model application. The method is demonstrated for model-based process design and aims at mitigating a worst-case realization of the process design. The proposed formulation results in a min–max–min problem and is based on bounded-error OED. The method is illustrated via an ad hoc solution method using two examples, a simple illustrative example and the van de Vusse reaction, that show the differences between typical and the new tailored OED method: experimental designs can be considered good using the latter method, while the same design would be considered bad with the former methods.