Tight Size Distribution Research Articles

Microcrystals for dissolution rate enhancement of poorly water-soluble drugs

Slight dissolution rates related to poor water-solubility are one of the well-known difficulties to be covered during the development of new drug substances. The poorly water-soluble drug ECU-01, a low molecular enzyme-inhibitor with anti-inflammatory properties for oral administration, shows a poor dissolution rate. This study is intended to enhance the drug dissolution rate by using microcrystals. The common way for micronization is the milling of previously formed larger crystals. However, milling shows several disadvantages as the newly created surfaces are thermodynamically activated due to the high energy input and not naturally grown. In this study microcrystals were not produced using any cutting up techniques, but only by association. Naturally grown microcrystals were prepared by a precipitation method in the presence of stabilizing agents (e.g. gelatin, chitosan, different types of cellulose ethers) followed by spray-drying of the formed dispersion. First the drug was dissolved in acetone and then precipitated by rapid pouring an aqueous solution of the stabilizer into the drug solution. Particularly, cellulose ethers were able to form stable and homogeneous dispersions of microcrystals (mean particle size=1 μm) showing a tight particle size distribution. By spray-drying, the drug powder was obtained. The dissolution rate is significantly enhanced (common drug: 4% after 20 min/microcrystals 93% after 20 min) due to the large surface, which is hydrophilized by adsorbed stabilizers as shown by the decreased contact angle (65 and 30°, respectively).

Production of Nanostructures Under Ultraturbulent Collision Reaction Conditions - Application to Catalysts, Superconductors, CMP Abrasives, Ceramics, and Other Nanoparticles

AbstractThe development, operation and applications of a novel continuous chemical reactor system are described. The system, known as a Multiple Stream Mixer/Reactor (or MMR), produces nanoparticles by direct precipitation from two or more reactant solution streams in an extreme energy density, ultraturbulent, collision reaction region. Sensors and a control system are employed to assure constant mixing conditions and desired stoichiometry in the reaction region. The interaction chamber is designed to allow macro-, meso- and micromixing during processing. This allows control of product purity, yield, size, size distribution, and phase purity. Typical nanoparticle diameters in the one to ten nanometer range are often achievable, with tight size distribution. The MMR can be scaled from development quantities to tons/hour for production applications.

Gas atomization of nickel aluminide powders: A.Zambon et al. (University of Padua, Padua, Italy.) Powder Metall., vol 42, no 3, 1999, 275–277

The influence of atomising gas pressure on particle shape of inert gas atomised Al and Mg powders was investigated in a pilot plant gas atomiser using an IN4/ON18/3.5–4.0 type `confined design' nozzle. In the tests for Mg powder production, argon at 1.05–1.85 MPa and helium at 1.03–1.77 MPa were used as the atomising agent. A controlled amount of oxygen in the gaseous phase was kept constant at 0.5% by volume while atomising gas pressure was changed from 1.06 to 1.85 MPa for argon runs and from 1.02 to 1.85 MPa for helium runs during Al powder production. The morphology of powder particles was examined by SEM. Powders were sized using dry sieving (under Ar for Mg powders) and wet sieving. The Sauter mean diameter varied from 12.97 to 24.13 μm for Mg powders and from 9.2 to 20.7 μm for Al powders (dry sieve) depending on the atomising gas and its pressure. Size distribution curves indicated bi-modal distribution in the powder. The fine size range of the particles was spherical and the coarse size range exhibited particles with oblong and round shapes when the argon pressure was high during Mg powder production. Argon with low pressure caused production of completely spherical Mg powder particles with a tight size distribution. In helium runs of Mg powders, the coarse size range of the powder was more irregular with rough surfaces in high atomising gas pressure tests than that in low pressure ones. In Al powders, the same morphological features of powder particles were observed but the effect of the gas pressure on Al powder particle shape was lower. This is due to the more efficient secondary break up in the process of atomisation of Al compared with Mg.

Evaluation of Spinning Disk Reactor Technology for the Manufacture of Pharmaceuticals

A continuously operating spinning disk reactor (SDR) displayed distinct advantages over batch processing techniques when several commercially relevant processes for the manufacture of pharmaceuticals as test reactions were investigated. It proved to be a useful tool for revealing intrinsically fast kinetics as well as for optimizing processes with such kinetics. Very encouraging results were achieved for a phase-transfer-catalyzed (ptc) Darzen's reaction to prepare a drug intermediate and the recrystallization of an active pharmaceutical ingredient (API). In comparison to presently used batch processes, the ptc reaction resulted in a reaction with 99.9% reduced reaction time, 99% reduced inventory, and 93% reduced impurity level. The recrystallization yielded particles with a tight particle size distribution and a mean size of around 3 μm. Reactor modeling was in good agreement with the experimental results and highlighted the advantages of the process-intensified equipment with a production capacity of a...

Tuning of gas atomizer nozzles by use of water bench techniques : J.Shon, J.J.Dunkley. (Atomizing Systems Ltd, Sheffield, UK.)

The influence of atomising gas pressure on particle shape of inert gas atomised Al and Mg powders was investigated in a pilot plant gas atomiser using an IN4/ON18/3.5–4.0 type `confined design' nozzle. In the tests for Mg powder production, argon at 1.05–1.85 MPa and helium at 1.03–1.77 MPa were used as the atomising agent. A controlled amount of oxygen in the gaseous phase was kept constant at 0.5% by volume while atomising gas pressure was changed from 1.06 to 1.85 MPa for argon runs and from 1.02 to 1.85 MPa for helium runs during Al powder production. The morphology of powder particles was examined by SEM. Powders were sized using dry sieving (under Ar for Mg powders) and wet sieving. The Sauter mean diameter varied from 12.97 to 24.13 μm for Mg powders and from 9.2 to 20.7 μm for Al powders (dry sieve) depending on the atomising gas and its pressure. Size distribution curves indicated bi-modal distribution in the powder. The fine size range of the particles was spherical and the coarse size range exhibited particles with oblong and round shapes when the argon pressure was high during Mg powder production. Argon with low pressure caused production of completely spherical Mg powder particles with a tight size distribution. In helium runs of Mg powders, the coarse size range of the powder was more irregular with rough surfaces in high atomising gas pressure tests than that in low pressure ones. In Al powders, the same morphological features of powder particles were observed but the effect of the gas pressure on Al powder particle shape was lower. This is due to the more efficient secondary break up in the process of atomisation of Al compared with Mg.

Influence of atomising gas pressure on particle shape of Al and Mg powders

The influence of atomising gas pressure on particle shape of inert gas atomised Al and Mg powders was investigated in a pilot plant gas atomiser using an IN4/ON18/3.5–4.0 type `confined design' nozzle. In the tests for Mg powder production, argon at 1.05–1.85 MPa and helium at 1.03–1.77 MPa were used as the atomising agent. A controlled amount of oxygen in the gaseous phase was kept constant at 0.5% by volume while atomising gas pressure was changed from 1.06 to 1.85 MPa for argon runs and from 1.02 to 1.85 MPa for helium runs during Al powder production. The morphology of powder particles was examined by SEM. Powders were sized using dry sieving (under Ar for Mg powders) and wet sieving. The Sauter mean diameter varied from 12.97 to 24.13 μm for Mg powders and from 9.2 to 20.7 μm for Al powders (dry sieve) depending on the atomising gas and its pressure. Size distribution curves indicated bi-modal distribution in the powder. The fine size range of the particles was spherical and the coarse size range exhibited particles with oblong and round shapes when the argon pressure was high during Mg powder production. Argon with low pressure caused production of completely spherical Mg powder particles with a tight size distribution. In helium runs of Mg powders, the coarse size range of the powder was more irregular with rough surfaces in high atomising gas pressure tests than that in low pressure ones. In Al powders, the same morphological features of powder particles were observed but the effect of the gas pressure on Al powder particle shape was lower. This is due to the more efficient secondary break up in the process of atomisation of Al compared with Mg.

Ion beam effects on the formation of Ge and Si nanoclusters in silica thin films

We have observed that ion-beam-assisted deposition (IBAD) has important effects on the optical properties of nanoclusters of Si or Ge in silica thin films. Si or Ge nanocluster(nc)-containing, thin silica films were prepared both by evaporation (PVD) and ion-beam-assisted deposition (IBAD), along with post-deposition annealing. Ge-nc IBAD films contain smaller nanoclusters (3.8± 0.5 nm) with a much tighter size distribution than the PVD films (13±6 nm). The difference in cluster size leads to a shift of the peak position of photoluminescence (PL). Furthermore, X-ray diffraction (XRD) from Ge-nc containing silica films reveals that IBAD promotes the crystallization of semiconductor nc's at lower annealing temperatures and inhibits further growth with increasing annealing temperature. For the Si-system, a decreasing Si-nc size was observed for an increasing ion energy, which weakens the PL and produces an observable small blue shift in the peak of the PL.

Cross-flow and dead-end microfiltration of oily-water emulsion. Part I: Experimental study and analysis of flux decline

Microfiltration for the separation of oil-in-water emulsions has been investigated and a method of identifying fouling mechanisms applicable to microfiltration in general has been developed. For a variety of membranes, simultaneous experiments in both dead-end and cross-flow modes have been performed at various pressures, and in the latter case at different cross-flow velocities. The oil phase comprised dodecane at 1000 ppm. Initial fouling rates were very significant with the two polymeric membranes used but distinctly less severe with the Ceramesh membrane, possibly due to its tight pore size distribution. Good performance was achieved with this membrane under turbulent flow conditions. Flux decline and rates of permeate flow resistance change have been analysed using a new formulation of the equations illustrating a method of resistance mechanism recognition.

Recovery of therapeutic proteins from inclusion bodies: problems and process strategies

The initial recovery of product in the form of inclusion bodies has many attractive process features which have been exploited by the biotechnology industry. The product, being sequestered in a near homogeneous state in dense granules of tight size distribution, may be recovered at high purities on a multi-kilogram scale by cell disruption followed by centrifugation [ 5-61. Soluble cellular components may be depleted by cycles of centrifugation and resuspension in buffer, leaving cell debris and associated membrane-bound components as the major Contaminants of inclusion body preparations. Some of these membrane proteins in the debris can be removed from the insoluble inclusion body product by selective extraction using buffers such as Triton X-l00/urea, originally developed as general methods for solubilizing membrane proteins. Alternatively, the density difference between cell debris and inclusion body granules can be exploited by differential centrifugation in sucrose buffers, inclusion body material being collected in the solids discharge of the centrifugal separator and cell debris rejected in the supernatant. Using these methods large quantities of highly enriched recombinant product have been processed routinely. The requirement for the removal of cell debris and the soluble constituents of the host is not necessarily obligatory, especially when accumulation levels of > 50% total cell protein have been achieved. Cell breakage by high pressure homogenization and the subsequent centrifugation operations are expensive in terms of fixed capital costs and energy consumption. The alternative strategy of recovering the inclusion body protein by directly solubilizing the cell paste in a strongly denaturing solvent, such as 8 M-guanidinium hydrochloride has therefore been advocated by some workers [7]. The choice may sometimes be determined more by constraints downstream than by the economics of recovery. For example, the recovery of renatured foot and mouth disease virus VPI coat protein, expressed in E. coli inclusion body fractions, is reduced by the presence of high molecular mass cellular components [ 8 ] and many process schemes employ an initial purification step before the removal of the solubilizing solvent [9, lo]. Most of the commonly used solubilizing agents, guanidine hydrochloride, acid or alkaline buffers and ionic detergent, reduce the choice of these initial pre-refolding purification steps to gel filtration. Urea solvents have found favour as solubilizing agents because their use permits consecutive subtractive ion-exchange chromatography, thereby removing nucleic acids, phospholipids and electronegative contaminant proteins from the process stream. The major contaminants found in inclusion body preparations are peptidoglycans, lipids, nucleic acids, lipopolysaccharide and membrane-associated proteins. Although most of these components will dissolve under the harsh conditions often required to solubilize inclusion bodies, these substances are often poorly soluble under renaturing conditions and the bulk will precipitate without influencing the refolding of the recombinant product. The process stream may then be enriched further by centrifugation and filtration.

The role of support in the catalytic hydrogenation of benzene over ruthenium catalysts

With worldwide petroleum resources dwindling and greenhouse gas emissions rising, it is urgent to find renewable replacements for petroleum-derived products. A biomass-derived chemical with high potential as a platform intermediate, γ-valerolactone (GVL) can be readily synthesized by hydrogenation of levulinic acid (LA), itself a common biomass intermediate, using supported Ru catalysts. To date the literature on many novel biomass conversion processes such as the hydrogenation of LA to GVL has focused more on the process and less on the catalyst.The goal of this work was to derive fundamental synthesis–structure–function relationships of Ru catalysts for LA hydrogenation using carbon- and alumina-supported Ru nanoparticles that have been synthesized in a rational, repeatable, scalable way. We have demonstrated that the method of strong electrostatic adsorption (SEA) yields well-dispersed, homogeneously distributed Ru particles with tight particle size distributions over both types of supports. SEA synthesis of well-dispersed nanoparticles results in higher activity than commercial Ru catalysts with higher Ru loadings. The dramatic, beneficial effect of potassium doping is reported for the first time. The carbon support yields higher inherent activity than alumina. Activity as a function of particle size appears to go through a maximum at about 1.5 nm for both supports and suggests hydrogenation of LA is structure sensitive to Ru particle size. Catalyst deactivation after 24 h occurs to significant extents (8–58%) mainly by nanoparticle sintering, but also by minor amounts of K loss in K-doped samples.

The Assessment of a New Range of Large Monosized Polystyrene Spheres and their Potential as Calibration Material for Particle Size Analysis Equipment

Large polystyrene spheres (nominally 5-, 7-, 10-, and 15-μm diameter) form a new range. The spheres have been sized using a Magiscan Image Analyzer, a scanning electron microscope, and a Coulter counter. Spheres of each nominal size have been found to have a tight size distribution.