Analysis of Cuticular Lipids of the Pharaoh Ant (Monomorium pharaonis) and Their Selective Adsorption on Insecticidal Zeolite Powders.

The pharaoh ant is a notorious and hard to eradicate pest, which poses a threat in hospitals, spreading pathogens and contaminating sterile equipment. When applied on ants, zeolites adsorb part of their epicuticular wax layer. The ants are then vulnerable to desiccation, since this layer regulates water exchange. We analyzed the chemical composition of this wax layer using GC-MS (Gas Chromatography-Mass Spectrometry). A hexane wash of M. pharaonis foragers resulted in the identification of 53 components, four of which were not previously defined in Monomorium species. Selective adsorption of specific compounds on zeolites assisted in the identification of compounds which could not be separated on the GC column and allowed for the identification of three additional compounds. Zeolites show different affinities for the wax compounds depending on pore structure and chemical composition. Selective adsorption of alkanes on zeolites is also investigated in the fields of refinery processes and catalysis. Pore mouth and key lock adsorption mechanisms and selectivity according to molecular weight and branching, investigated in these fields, are also involved in adsorption processes of epicuticular waxes. The insecticidal activity of a zeolite is related to adsorption selectivity rather than capacity. One of the best adsorbing zeolites showed limited insecticidal activity and can be considered as a non-lethal alternative for epicuticular wax sampling.

In Situ Solid-State (13)C NMR Observation of Pore Mouth Catalysis in Etherification of ß-Citronellene with Ethanol on Zeolite Beta.

The reaction mechanism of etherification of ß-citronellene with ethanol in liquid phase over acid zeolite beta is revealed by in situ solid-state (13)C NMR spectroscopy. Comparison of (13)C Hahn-echo and (1)H-(13)C cross-polarization NMR characteristics is used to discriminate between molecules freely moving in liquid phase outside the zeolite and molecules adsorbed inside zeolite pores and in pore mouths. In the absence of ethanol, ß-citronellene molecules enter zeolite pores and react to isomers. In the presence of ethanol, the concentration of ß-citronellene inside zeolite pores is very low because of preferential adsorption of ethanol. The etherification reaction proceeds by adsorption of ß-citronellene molecule from the external liquid phase in a pore opening where it reacts with ethanol from inside the pore. By competitive adsorption, ethanol prevents the undesired side reaction of ß-citronellene isomerization inside zeolite pores. ß-citronellene etherification on zeolite beta is suppressed by bulky base molecules (2,4,6-collidine and 2,6-ditertiarybutylpyridine) that do not enter the zeolite pores confirming the involvement of easily accessible acid sites in pore openings. The use of in situ solid-state NMR to probe the transition from intracrystalline catalysis to pore mouth catalysis depending on reaction conditions is demonstrated for the first time. The study further highlights the potential of this NMR approach for investigations of adsorption of multicomponent mixtures in general.

Membrane remodeling processes induced by phospholipase action.

Important cellular events such as division require drastic changes in the shape of the membrane. These remodeling processes can be triggered by the binding of specific proteins or by changes in membrane composition and are linked to phospholipid metabolism for which dedicated enzymes, named phospholipases, are responsible. Here wide-field fluorescence microscopy is used to visualize shape changes induced by the action of phospholipase A1 on dye-labeled supported membranes of POPC (1-palmitoyl-2-oleoly-sn-glycero-3-phosphocholine). Time-lapse imaging demonstrates that layers either shrink and disappear or fold and collapse into vesicles. These vesicles can undergo further transformations such as budding, tubulation, and pearling within 5 min of formation. Using dye-labeled phospholipases, we can monitor the presence of the enzyme at specific positions on the membrane as the shape transformations occur. Furthermore, incorporating the products of hydrolysis into POPC membranes is shown to induce transformations similar to those observed for enzyme action. The results suggest that phospholipase-mediated hydrolysis plays an important role in membrane transformations by altering the membrane composition, and a model is proposed for membrane curvature based on the presence and shape of hydrolysis products.

Selective and reversible ammonia gas detection with nanoporous film functionalized silicon photonic micro-ring resonator.

Portable, low cost and real-time gas sensors have a considerable potential in various biomedical and industrial applications. For such applications, nano-photonic gas sensors based on standard silicon fabrication technology offer attractive opportunities. Deposition of high surface area nano-porous coatings on silicon photonic sensors is a means to achieve selective, highly sensitive and multiplexed gas detection on an optical chip. Here we demonstrate selective and reversible ammonia gas detection with functionalized silicon-on-insulator optical micro-ring resonators. The micro-ring resonators are coated with acidic nano-porous aluminosilicate films for specific ammonia sensing, which results in a reversible response to NH(3)with selectivity relative to CO(2). The ammonia detection limit is estimated at about 5 ppm. The detectors reach a steady response to NH(3) within 30 and return to their base level within 60 to 90 seconds. The work opens perspectives on development of nano-photonic sensors for real-time, non-invasive, low cost and light weight biomedical and industrial sensing applications.

Continuous synthesis process of hexagonal nanoplates of P6m ordered mesoporous silica.

Hexagonally ordered mesoporous silica coined COK-12 was synthesized in a continuous process by combining streams of sodium silicate and citric acid/sodium citrate buffered solution of (ethylene oxide)(20)-(propylene oxide)(70)-(ethylene oxide)(20) triblock copolymer (Pluronic P123) from separate reservoirs. COK-12 precipitated spontaneously upon combining both streams at nearly neutral pH and ambient temperature. Stable intermediates of the COK-12 formation process could be prepared by limiting sodium silicate addition. Investigation of these intermediates using small-angle X-ray scattering revealed COK-12 formed via an assembly process departing from spherical uncharged core-shell P123-silica micelles. The sterical stabilization of these micelles decreased upon accumulation of silicate oligomers in their shell. Aggregation of the spherical micelles led to cylindrical micelles, which aligned and adopted the final hexagonal organization. This unprecedentedly fast formation of P6m ordered mesoporous silica was caused by two factors in the synthesis medium: the neutral pH favoring uncharged silicate oligomers and the high salt concentration promoting hydrophobic interactions with surfactant micelles leading to silica accumulation in the PEO shell. The easy continuous synthesis process is convenient for large-scale production. The platelet particle morphology with short and identical internal channels will be advantageous for many applications such as pore replication, nanotube or fiber growth, catalytic functionalization, drug delivery, film and sensor development, and in nano dyes as well as for investigation of pore diffusion phenomena.

Comparison between hot-melt extrusion and spray-drying for manufacturing solid dispersions of the graft copolymer of ethylene glycol and vinylalcohol.

PURPOSE: To investigate the effect of the manufacturing method (spray-drying or hot-melt extrusion) on the kinetic miscibility of miconazole and the graft copolymer poly(ethyleneglycol-g-vinylalcohol). The effect of heat pre-treatment of solutions used for spray-drying and the use of spray-dried copolymer as excipient for hot-melt extrusion was investigated. METHOD: The solid dispersions were prepared at different drug-polymer ratios and analyzed with modulated differential scanning calorimetry and X-ray powder diffraction. RESULTS: Miconazole either mixed with the PEG-fraction of the copolymer or crystallized in the same or a different polymorph as the starting material. The kinetic miscibility was higher for the solid dispersions obtained from solutions which were pre-heated compared to those spray-dried from solutions at ambient temperature. Hot-melt extrusion resulted in an even higher mixing capability. Here the use of the spray-dried copolymer did not show any benefit concerning the kinetic miscibility of the drug and copolymer, but it resulted in a remarkable decrease in the torque experienced by the extruder allowing extrusion at lower temperature and torque. CONCLUSION: The manufacturing method has an influence on the mixing capacity and phase behavior of solid dispersions. Heat pre-treatment of the solutions before spray-drying can result in a higher kinetic miscibility. Amorphization of the copolymer by spray-drying before using it as an excipient for hot-melt extrusion can be a manufacturing benefit.

Insights on a Hierarchical MFI Zeolite: A Combined Spectroscopic and Catalytic Approach for Exploring the Multilevel Porous System Down to the Active Sites.

The hierarchization of zeolites to overcome the major drawbacks related to molecular diffusion limitation in micropores is a popular concept in heterogeneous catalysis. Despite the constant increase of new synthesis strategies to produce such hierarchical systems, the deep knowledge of their structural arrangement and how the zeolitic lattice is organized in a multilevel porous system is often missing. This information is essential to design a structure, tuning the porosity and the distribution of easily accessible active sites, and successively controlling the catalytic properties. In the present work, the synthesis of one of the most sophisticated forms of the hierarchical ZSM-5 zeolite has been reproduced, obtaining two multilevel porous materials with different crystallinity degrees, with the final aim of investigating and clarifying the finest features of their active sites. For this purpose, an extended characterization step by means of a unique multitechnique approach has been performed, thus revealing the active site nature, abundance, and distribution. IR spectroscopy with different molecular probes and a targeted catalytic test based on the hydroconversion reaction of n-decane were the toolbox for disclosing how the MFI lattice takes part in the hierarchical structure and how it, working in synergy with the mesoporous system, confers to this material a totally new shape-size selectivity. Merging the information obtained for the synthesized hierarchical zeolite with the characterization results of two reference materials (a mesoporous aluminum-containing MCM-41 and a microporous commercial ZSM-5), it was possible to define an internal and external map of the pore network of this complex and unique molecular sieve, where strong Brønsted acidic sites are located at the mouth of the MFI micropores and, at the same time, exposed at the surface of the mesoporous channels. Hence, the possibility of easily releasing bulky products is ensured and the application possibilities of the MFI lattice are expanded beyond cracking reactions.

Implant functionalization with mesoporous silica: A promising antibacterial strategy, but does such an implant osseointegrate?

OBJECTIVES: New strategies for implant surface functionalization in the prevention of peri-implantitis while not compromising osseointegration are currently explored. The aim of this in vivo study was to assess the osseointegration of a titanium-silica composite implant, previously shown to enable controlled release of therapeutic concentrations of chlorhexidine, in the Göttingen mini-pig oral model. MATERIAL AND METHODS: Three implant groups were designed: macroporous titanium implants (Ti-Porous); macroporous titanium implants infiltrated with mesoporous silica (Ti-Porous + SiO2 ); and conventional titanium implants (Ti-control). Mandibular last premolar and first molar teeth were extracted bilaterally and implants were installed. After 1 month healing, the bone in contact with the implant and the bone regeneration in the peri-implant gap was evaluated histomorphometrically. RESULTS: Bone-to-implant contact and peri-implant bone volume for Ti-Porous versus Ti-Porous + SiO2 implants did not differ significantly, but were significantly higher in the Ti-Control group compared with Ti-Porous + SiO2 implants. Functionalization of titanium implants via infiltration of a SiO2 phase into the titanium macropores does not seem to inhibit implant osseointegration. Yet, the importance of the implant macro-design, in particular the screw thread design in a marginal gap implant surgery set-up, was emphasized by the outstanding results of the Ti-Control implant. CONCLUSIONS: Next-generation implants made of macroporous Ti infiltrated with mesoporous SiO2 do not seem to compromise the osseointegration process. Such implant functionalization may be promising for the prevention and treatment of peri-implantitis given the evidenced potential of mesoporous SiO2 for controlled drug release.

Solubility increases associated with crystalline drug nanoparticles: methodologies and significance.

In this manuscript, the determination of solubility of crystalline drug nanosuspensions by a range of methods is critically investigated. As the determinations of solubility were performed in the presence of the solubilizing nanosuspension stabilizer d-α-tocopherol polyethylene glycol 1000 succinate (TPGS), the potential effects of this excipient on the measurements were studied first. Solubility data of nanosuspensions of itraconazole, loviride, phenytoin and naproxen were generated using different methodologies. Data obtained using separation-based methodologies (centrifugation, filtration and ultracentrifugation) proved to be of limited use, due to poor nanoparticle separation efficiencies and/or significant adsorption of TPGS onto the nanoparticle surfaces. Light scattering and turbidity were found to be more suitable for the determination of nanosuspension solubility. The obtained data show that, unlike earlier reports, the solubility increases due to nanosizing are small, with measured increases of only 15%. These solubility increases are in fair agreement with what would be predicted based on the Ostwald-Freundlich equation.

High-Performance CO2-Selective Hybrid Membranes by Exploiting MOF-Breathing Effects.

Conventional CO2 separation in the petrochemical industry via cryogenic distillation or amine-based absorber-stripper units is energy-intensive and environmentally unfriendly. Membrane-based gas separation technology, in contrast, has contributed significantly to the development of energy-efficient systems for processes such as natural gas purification. The implementation of commercial polymeric membranes in gas separation processes is restricted by their permeability-selectivity trade-off and by their insufficient thermal and chemical stability. Herein, we present the fabrication of a Matrimid-based membrane loaded with a breathing metal-organic framework (MOF) (NH2-MIL-53(Al)) which is capable of separating binary CO2/CH4 gas mixtures with high selectivities without sacrificing much of its CO2 permeabilities. NH2-MIL-53(Al) crystals were embedded in a polyimide (PI) matrix, and the mixed-matrix membranes (MMMs) were treated at elevated temperatures (up to 350 °C) in air to trigger PI cross-linking and to create PI-MOF bonds at the interface to effectively seal the grain boundary. Most importantly, the MOF transitions from its narrow-pore form to its large-pore form during this treatment, which allows the PI chains to partly penetrate the pores and cross-link with the amino functions at the pore mouth of the NH2-MIL-53(Al) and stabilizes the open-pore form of NH2-MIL-53(Al). This cross-linked MMM, with MOF pore entrances was made more selective by the anchored PI-chains and achieves outstanding CO2/CH4 selectivities. This approach provides significant advancement toward the design of selective MMMs with enhanced thermal and chemical stabilities which could also be applicable for other potential applications, such as separation of hydrocarbons (olefin/paraffin or isomers), pervaporation, and solvent-resistant nanofiltration.

High-throughput study of phenytoin solid dispersions: formulation using an automated solvent casting method, dissolution testing, and scaling-up.

A high-throughput experimentation method for studying the dissolution of phenytoin, a poorly water soluble drug, was developed and validated. Solid dispersions with 12 excipients (7 polymers and 5 surfactants) were prepared and tested. Each excipient was screened with three drug loadings: 10, 20, and 40% (w/w). Each solid dispersion was prepared in triplicate, for a total of 108 samples. The drug dissolution was studied in simulated gastric fluid without pepsin plus 1% sodium laurylsulfate. This study led to the identification of three improved formulations, exhibiting an extent of dissolution higher than 90% after both 30 and 60 min. The HTE results could be reproduced at a larger scale using a conventional solvent evaporating method, proving the reliability of the HTE protocol.

Microcrystalline cellulose, a useful alternative for sucrose as a matrix former during freeze-drying of drug nanosuspensions - a case study with itraconazole.

Itraconazole nanosuspensions, stabilized with 10% TPGS (relative to the weight of itraconazole), were transformed into nanoparticulate powders by freeze-drying. The crystalline itraconazole nanoparticles showed peak broadening in the X-ray powder diffraction spectra and a lower melting point as inferred from differential scanning calorimetry. As it was found that freeze-drying compromised dissolution behavior, sucrose was added as a matrix, former (50,100 and 200%, relative to the weight of itraconazole). Higher amounts of sucrose unexpectedly resulted in a decrease in the dissolution rate. After thorough evaluation of the powders, it was found that whereas higher sucrose content showed a cryoprotective effect, agglomeration during the final phase of the subsequent drying step tended to increase with higher amounts of sucrose. Therefore, microcrystalline cellulose (MCC) was evaluated as an alternative matrix former. The inclusion of MCC resulted in fast dissolution that increased with increasing amounts of MCC [for powders containing 50%,100% and 200% MCC, (relative to the weight of itraconazole), the times required for 63.2% release were 10.5+/-0.7, 6.4+/-1.2 and 3.1+/-0.5min, respectively]. The dissolution profiles showed an initial phase of burst dissolution, followed by a phase of slower release. As the fraction showing burst dissolution increased with higher MCC content, the system holds promise to maintain the dissolution enhancing properties of nanoparticles in the dry form.

Agglomeration of mesoporous silica by melt and steam granulation. part II: screening of steam granulation process variables using a factorial design.

The objectives of this study were to identify the key process parameters during steam granulation of disordered mesoporous silica material Syloid® 244 FP (244) and to compare two different binders: polyvinylpyrrolidone (PVP) K25 and hydroxypropylmethyl cellulose (HPMC). Itraconazole (ITZ) was selected as the model compound for the development of an oral dosage form for enhanced release. Six factors: binder content, steam amount, mixing time, impeller speed, spray pause time, and filler content were investigated using a two-level quarter-fraction factorial design of experiment (DOE) for each binder type. As experimental responses, characteristics correlating to both granules and tablets were selected. Granules prepared from PVP resulted in an overall higher bulk density, granule size, increased flow properties, and better compression and compaction behavior. Although granulation with PVP resulted in the most ITZ to extract from the pores during processing, the premature drug release was less than 5%. The results of the DOE indicate that the risk of extracting the drug from the pores during processing is governed both by the process parameters and the binder properties. Centerpoint replicates of granules prepared with HPMC were highly variable.

Agglomeration of mesoporous silica by melt and steam granulation. Part I: a comparison between disordered and ordered mesoporous silica.

The objective of this study was to compare agglomerations by melt and steam granulation of ordered, COK-12, and disordered, Syloid(®) 244 FP (244), mesoporous silica material. Poloxamer 188 (P188) and polyvinylpyrrolidone K25 (PVP) were chosen as binders for melt and steam granulation, respectively. The poorly water-soluble compound, itraconazole (ITZ), was selected for the development of an immediate-release oral dosage form. Steam granulation resulted in the largest granules, however, the slowest release. Compression behavior and tablet properties of steam-granulated material prepared with COK-12 and 244 were similar. As determined by X-ray powder diffraction, melt granulation resulted in the most ITZ to extract from the pores during processing. However, the enhanced release rate was still maintained when compared with the crystalline form. Moreover, no additional drug extraction was observed following the 6 month storage in 25°C/60% relative humidity (RH) and 40°C/75%RH. P188 diffraction peaks were present in the 244 melt-granulated material, but disappeared because of the degradation following 1 week in 40°C/75%RH conditions. The differential scanning calorimetry analysis indicated that the degradation of P188 already occurred during the granulation process itself. Based on these results, steam granulation with PVP is the preferred method over melt granulation with P188.

Upscaling of the hot-melt extrusion process: comparison between laboratory scale and pilot scale production of solid dispersions with miconazole and Kollicoat IR.

Since only limited amount of drug is available in early development stages, the extruder design has evolved towards smaller batch sizes, with a more simple design. An in dept study about the consequences of the differences in design is mandatory and little can be found in literature. Miconazole and Kollicoat IR were used as model drug and carrier for this study. Two series of solid dispersions were made with a laboratory scale (internal circulation-simple screw design) and a pilot scale extruder (continuous throughput-modular screw design). Efforts were made to match the operating parameters as close as possible (residence time, extrusion temperature and screw speed). The samples were analyzed with modulated DSC straight after production and after exact 24h and 15 days storage at -26 °C. The kinetic miscibility of the samples prepared with the laboratory scale extruder was slightly higher than the samples prepared with the pilot scale extruder. As the solid dispersions with high drug load were unstable over time, demixing occurred, slightly faster for the samples prepared with the laboratory scale extruder. After 15 days, the levels of molecular mixing were comparable, pointing to the predictive value of samples prepared on laboratory scale.

Bone tissue response to porous and functionalized titanium and silica based coatings.

BACKGROUND: Topography and presence of bio-mimetic coatings are known to improve osseointegration. The objective of this study was to evaluate the bone regeneration potential of porous and osteogenic coatings. METHODOLOGY: Six-implants [Control (CTR); porous titanium coatings (T1, T2); thickened titanium (Ti) dioxide layer (TiO(2)); Amorphous Microporous Silica (AMS) and Bio-active Glass (BAG)] were implanted randomly in tibiae of 20-New Zealand white rabbits. The animals were sacrificed after 2 or 4 weeks. The samples were analyzed histologically and histomorphometrically. In the initial bone-free areas (bone regeneration areas (BRAs)), the bone area fraction (BAF) was evaluated in the whole cavity (500 µm, BAF-500), in the implant vicinity (100 µm, BAF-100) and further away (100-500 µm, BAF-400) from the implant. Bone-to-implant contact (BIC-BAA) was measured in the areas where the implants were installed in contact to the host bone (bone adaptation areas (BAAs)) to understand and compare the bone adaptation. Mixed models were used for statistical analysis. PRINCIPAL FINDINGS: After 2 weeks, the differences in BAF-500 for different surfaces were not significant (p>0.05). After 4 weeks, a higher BAF-500 was observed for BAG than CTR. BAF-100 for AMS was higher than BAG and BAF-400 for BAG was higher than CTR and AMS. For T1 and AMS, the bone regeneration was faster in the 100-µm compared to the 400-µm zone. BIC-BAA for AMS and BAG was lower after 4 than 2 weeks. After 4 weeks, BIC-BAA for BAG was lower than AMS and CTR. CONCLUSIONS: BAG is highly osteogenic at a distance from the implant. The porous titanium coatings didn't stimulate bone regeneration but allowed bone growth into the pores. Although AMS didn't stimulate higher bone response, it has a potential of faster bone growth in the vicinity compared to further away from the surface. BIC-BAA data were inconclusive to understand the bone adaptation.

Controlled release of chlorhexidine antiseptic from microporous amorphous silica applied in open porosity of an implant surface.

Amorphous microporous silica (AMS) serving as a reservoir for controlled release of a bioactive agent was applied in the open porosity of a titanium coating on a Ti-6Al-4V metal substrate. The pores of the AMS emptied by calcination were loaded with chlorhexidine diacetate (CHX) via incipient wetness impregnation with CHX solution, followed by solvent evaporation. Using this CHX loaded AMS system on titanium substrate sustained release of CHX into physiological medium was obtained over a 10 day-period. CHX released from the AMS coating was demonstrated to be effective in killing planktonic cultures of the human pathogens Candida albicans and Staphylococcus epidermidis. This surface modification of titanium bodies with AMS controlled release functionality for a bioactive compound potentially can be applied on dental and orthopaedic implants to abate implant-associated microbial infection.

Characterization of the copolymer poly(ethyleneglycol-g-vinylalcohol) as a potential carrier in the formulation of solid dispersions.

In order to fully exploit the graft copolymer poly(ethyleneglycol-g-vinylalcohol) (EG/VA) in the formulation of solid dispersions, a characterization of its phase behavior before, during and after spray-drying and hot-melt extrusion is performed. Solid state characterization was performed using MDSC and XRPD. The effect of heating/cooling rate on the degree of crystallinity was studied using HPer DSC and ultra-fast chip calorimetry. EG/VA consists of two semi-crystalline fractions, one corresponding to the polyethyleneglycol (PEG) fraction (T(g)=-57 degrees C, T(m)=15 degrees C) and one corresponding to the polyvinylalcohol (PVA) fraction (T(g)=45 degrees C, T(m)=212 degrees C). XRPD analysis confirmed its semi-crystallinity, and EG/VA showed Bragg reflections comparable to those of PVA. Spray-drying at a temperature lower than 170 degrees C resulted in amorphization of the PVA fraction, while after hot-melt extrusion at different temperatures, the crystallinity of this fraction increases. In both cases, the PEG fraction is not influenced. Plasticization of the amorphous domains of the PEG or PVA fraction of the copolymer was dependent on the type and concentration of plasticizer, suggesting that also other small organic molecules like drugs may not homogeneously mix with both amorphous domains. A controlled cooling rate of 3000 degrees C/s was necessary to make the copolymer completely amorphous.

A screening study of surface stabilization during the production of drug nanocrystals.

In order to establish a knowledge base for nanosuspension production, a screening was performed on 13 different stabilizers at 3 concentrations for 9 structurally different drug compounds. Concerning the stabilizers tested, the group of semi-synthetic polymers was the least performant (stable nanosuspensions were obtained in only 1 out of 10 cases). For the linear synthetic polymers, better results were obtained with povidones, however poly(vinyl alcohol) did not result in adequate stabilization. The synthetic copolymers showed even higher success rates, resulting in nanosuspensions in two out of three cases when applied at a 100 wt% concentration (relative to the drug weight). Finally, the surfactants gave the best results, with TPGS being successful at concentrations of 25 or 100 wt% of the drug weight for all compounds tested. From the point of view of drug compound, large differences could be observed upon evaluation of the relative number of formulations of that compound resulting in nanosuspensions. It was found that the hydrophobicity of the surfaces, as estimated by the adsorbed amount of TPGS per unit of surface area of nanosuspensions stabilized with 25 wt% TPGS, was decisive for the agglomeration tendency of the particles and hence the ease of nanosuspensions stabilization.

Itraconazole/TPGS/Aerosil200 solid dispersions: characterization, physical stability and in vivo performance.

Solid dispersions were successfully prepared by co-spray-drying of TPGS-stabilized itraconazole nanosuspensions with Aerosil200, followed by heat treatment of the powders. The itraconazole/Aerosil200 weight ratios amounted to 50/50, 30/70, 40/60 and 20/80. The itraconazole content of the powders was close to the expected value, with relative errors between 0.3% and 7.8%. X-ray powder diffraction (XRPD), solid state NMR (SSNMR) and differential scanning calorimetry (DSC) evaluation on the powders revealed the formation of amorphous itraconazole and the absence of glassy itraconazole. Dissolution of the powders was enhanced compared to crystalline and glassy itraconazole (a 2-dimensional structured form of itraconazole). However, no clear trend could be observed between drug loading and dissolution performance of the solid dispersions. Upon storage, conversion to crystalline itraconazole was observed for the 50/50 powder based on XRPD, SSNMR and DSC measurements. Although the 40/60 powder remained X-ray amorphous upon storage, DSC did reveal that a small fraction (7.5+/-1.6% after 10 months of storage) of itraconazole crystallized upon storage. For the 30/70 and 20/80 dispersions, no crystallization could be seen. After 10 months of storage, important changes in the dissolution behavior of the powders were observed. A decrease in dissolution performance was seen for the 50/50 dispersion, which could be attributed to the crystallization of itraconazole. On the other hand, the 40/60, 30/70 and 20/80 dispersions showed an increase in dissolution rate (more than 60% after 10 min). Although not completely clear at this stage, adsorption of itraconazole onto the Aerosil200 surface during storage might be responsible for this behavior. Finally, in vivo experiments were performed in the rat. Oral bioavailability of the 30/70 dispersion was, although lower compared to the marketed Sporanox formulation, significantly enhanced compared to the crystalline drug.