Micronization of Pharmaceutical Substances by Rapid Expansion of Supercritical Solutions (RESS): Experiments and Modeling

An increasing number of newly developed pharmaceutical substances are poorly soluble in both aqueous and organic media. Thus, the application of oral or injectable drugs is often limited by its low bioavailability. An alternative and promising method to improve the bioavailability of pharmaceutical agents is the production of nanoscale particles by the rapid expansion of supercritical solutions (RESS). Our research is aimed towards an improved understanding of the underlying physical phenomena of the relationship between the process conditions and the particle characteristics. Therefore, experimental investigations and numerical simulations were performed. RESS experiments with the pharmaceutical substances β‐sitosterol, griseofulvin, and ibuprofen led to particle sizes in the range of 240±80 nm. In addition, as one step towards intravenous application of poorly soluble drugs, β‐sitosterol was used to produce aqueous suspensions of a water‐insoluble drug with a particle size smaller than or equal to those produced by RESS into air. RESS modeling is focused on the flow through the nozzle, the supersonic free jet, the mach shock, and particle growth in the expansion unit. The comparison with experimental results shows a good agreement in the general trends but does not match exactly the measured mean particle sizes.     

Glass transition of the two distinct single-chain particles of poly(N-isopropylacrylamide)

Two distinct single-chain particles of poly(N-isopropylacrylamide) (PNIPAM) in the state of loose coil and compact globule, have been prepared successfully below and above the lower critical solution temperature (LCST) in extreme dilute aqueous solution by the freeze-drying method, respectively. During the preparation of the compact globular single-chain sample, the surfactant of sodium n-dodecyl sulfate (SDS) was added into the system to prevent aggregation of globular single chains formed at a temperature above the LCST. After all the coil has been transformed into the compact globular particle, the SDS molecules were removed by dialysis. The glass transition temperature (T_g) of the two single-chain samples has been measured by differential scanning calorimetery (DSC) in comparison with that of bulk polymer. It was found that the T_g of the single-chain sample in compact-globule state was very near to that of the bulk polymer, whereas the T_g of the single-chain sample in loose-coil state was approximately 6 K lower than that of the bulk polymer. After treating the sample with repeated DSC cycles, the T_g of the single-chain sample in loose-coil state rose up successively near to that of the bulk polymer. These results have been explained in terms of the effect of entanglement on the mobility of the polymer segments in the two distinct single-chain samples.     

Supercritical fluid micronization of risperidone pharmaceutical substance

A comparative study of the supercritical fluid micronization of risperidone pharmaceutical substance with an initial particle size of 50 to 100 μm by the RESS and SAS methods aimed at increasing the bioavailability of risperidone as a drug was performed. Both methods makes it possible to prepare risperidone particle of various forms, 5–20 μm in size. However, the SAS method is preferable, because in contrast to RESS, it does not cause contamination of risperidone with organic solvents used in both processes or any other impurities and also makes it possible to vary the shape and size of particles. It is shown that, during SAS micronization, the polymorphic form of risperidone changes from triclinic to monoclinic.     

Preparation of alkaline solid polymer electrolyte based on PVA-TiO2-KOH-H2O and its performance in Zn-Ni battery

A novel composite alkaline polymer electrolyte based on poly(vinyl alcohol) (PVA) polymer matrix, titanium dioxide (TiO₂) ceramic fillers, KOH, and H₂O was prepared by a solution casting method. The properties of PVA-TiO₂-KOH alkaline polymer electrolyte films were studied by X-ray diffraction (XRD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and AC impedance techniques. DSC and XRD results showed that the domain of amorphous region in the PVA polymer matrix augmented when TiO₂ filler was added. The SEM result showed that TiO₂ particles dispersed into the PVA matrix although some TiO₂ aggregates of several micrometers were formed. The alkaline polymer electrolyte showed excellent electrochemical properties. The room temperature (20 °C) ionic conductivity values of typical samples were between 0.102 and 0.171 S cm⁻¹. The Zn-Ni secondary battery with the alkaline polymer electrolyte PVA-TiO₂-KOH had excellent electrochemical property at the low charge-discharge rate.     

ICPAQGP2001: Conference summary

I review recent progress in ultrarelativistic nucleus-nucleus collisions, and the connection of this field to modern QCD theory of deconfinement and/or chiral symmetry restoration. The talks at this Conference have shown a convergence of data and theory as far as the CERN SPS investigations at √s = 17 GeV are concerned; the parton-hadron phase boundary seems now located atT = 170 ± 10 MeV. New data from RHIC and direct photon production results from CERN have been shown that point out the field’s future direction: analysis of partonic matter atT > 200 MeV. Astrophysics analysis was shown to be linked crucially to further theoretical progress with non-perturbative QCD.     

Molecular Dynamics simulation of a polymer chain translocating through a nanoscopic pore

The detection of linear polymers translocating through a nanoscopic pore is a promising idea for the development of new DNA analysis techniques. However, the physics of constrained macromolecules and the fluid that surrounds them at the nanoscopic scale is still not well understood. In fact, many theoretical models of polymer translocation neglect both excluded-volume and hydrodynamic effects. We use Molecular Dynamics simulations with explicit solvent to study the impact of hydrodynamic interactions on the translocation time of a polymer. The translocation time τ that we examine is the unbiased (no charge on the chain and no driving force) escape time of a polymer that is initially placed halfway through a pore perforated in a monolayer wall. In particular, we look at the effect of increasing the pore radius when only a small number of fluid particles can be located in the pore as the polymer undergoes translocation, and we compare our results to the theoretical predictions of Chuang et al. (Phys. Rev. E 65, 011802 (2001)). We observe that the scaling of the translocation time varies from τ ∼ N ^11/5 to τ ∼ N ^9/5 as the pore size increases (N is the number of monomers that goes up to 31 monomers). However, the scaling of the polymer relaxation time remains consistent with the 9/5 power law for all pore radii.     

A luminescent solar concentrator with 7.1% power conversion efficiency

The Luminescent Solar Concentrator (LSC) consists of a transparent polymer plate, containing luminescent particles. Solar cells are connected to one or more edges of the polymer plate. Incident light is absorbed by the luminescent particles and re‐emitted. Part of the light emitted by the luminescent particles is guided towards the solar cells by total internal reflection. Since the edge area is smaller than the receiving one, this allows for concentration of sunlight without the need for solar tracking. External Quantum Efficiency (EQE) and current–voltage (I –V) measurements were performed on LSC devices with multicrystalline silicon (mc‐Si) or GaAs cells attached to the sides. The best result was obtained for an LSC with four GaAs cells. The power conversion efficiency of this device, as measured at European Solar Test Installation laboratories, was 7.1% (geometrical concentration of a factor 2.5). With one GaAs cell attached to one edge only, the power efficiency was still as high as 4.6% (geometrical concentration of a factor 10). To our knowledge these efficiencies are among the highest reported for the LSC. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Viscosity at small scales in polymer melts

Flows around small colloidal particles of diameter b, or in thin films, capillaries, etc., cannot always be described in terms of the macroscopic polymer viscosity. We discuss these features for entangled polymer melts, where two distinct regimes can be found: (a) the thin regime where b is smaller than the coil radius R₀, but larger than the diameter of the Edwards tube; (b) the ultrathin regime, where . We consider (i) non adsorbing particles, where slippage may occur between the melt and the solid surface; (ii) “hairy” particles, which carry some bound polymer chains. We obtain scaling predictions for mobilities of spheres, of needles, and of clusters of particles. We also discuss translational and rotational diffusion of needles. Received 19 April 1999     

Chemically selective soft X‐ray patterning of polymers

The chemically selective modification of polymer mixtures by monochromated soft X‐rays has been explored using the high‐brightness fine‐focused 50 nm beam of a scanning transmission X‐ray microscope. Four different polymer systems were examined: a polymethylmethacrylate (PMMA) polyacrylonitrile (PAN) bilayer film; a PMMA‐blend‐PAN microphase‐separated film; a poly(MMA‐co‐AN) copolymer film; and a poly(ethyl cyanoacrylate) homopolymer film. A high level of chemically selective modification was achieved for the PMMA/PAN bilayer; in particular, irradiation at 288.45 eV selectively removed the carbonyl group from PMMA while irradiation at 286.80 eV selectively reduced the nitrile group of PAN, even when these irradiations were carried out at the same (x,y) position of the sample. In the last two homogenous polymer systems, similar amounts of damage to the nitrile and carbonyl groups occurred during irradiation at either 286.80 or 288.45 eV. This is attributed to damage transfer between the C[triple‐bond]N and C=O groups mediated by primary electrons, secondary electrons or radical/ionic processes, aided by their close spatial proximity. Although the overall thickness of the bilayer sample at 70 nm is smaller than the lateral line spreading of 100 nm, the interface between the layers appears to effectively block the transport of energy, and hence damage, between the two layers. The origins of the line spreading in homogeneous phases and possible origins of the damage blocking effect of the interface are discussed. To demonstrate chemically selective patterning, high‐resolution multi‐wavelength patterns were created in the PMMA/PAN bilayer system.     

Nanoparticle Distribution in Three‐Layer Polymer–Nanoparticle Composite Films: Comparison of Experiment and Theory

The distribution of hydrophobic nanoparticles deposited on a hydrophilic polymer film is investigated by scanning electron microscopy, transmission electron microscopy, and atomic force microscopy before and after spin‐coating a polymer solution on the particle film and drying it at room temperature. Various polymers and solvents are used. To reach equilibrium, all investigated systems are annealed additionally above the glass transition temperature (T_g) of the polymers. The compatibility of the interacting components is estimated by calculating their surface energy, solubility, and mutual interaction parameters. The experimental results show a redistribution of the particles on both interfaces of the polymer film. This corresponds to the calculated immiscibility of particles and polymers. The distribution of the nanoparticles at the interfaces is related mainly to the vapor pressure of the solvent, that is, kinetic effects during spin‐coating. Only minor contributions result from surface energy, solubility, and interaction parameters.     

Study of CdSe/CdS quantum dots in solutions and gels by small-angle X-ray scattering

The sizes of semiconductor nanocrystals of CdSe/CdS quantum dots (QDs) synthesized by the colloidal method were estimated using small-angle X-ray scattering. The distribution of QD nanocrystals in organic solvents of different polarities and in polymer gels and matrices is studied. Structural invariants of scattering QD particles (heterogeneities of the electron density)—namely, inertia radii and sizes, forms, and dispersive composition of particles—are determined. The contribution of scattering by QDs in solutions and gels is calculated. The effective sizes of particles and their aggregates are determined, and the parameters of the distribution over the QD sizes in organic solvents and polymer matrices are estimated. The typical distance between particles in samples is determined. The position of the maximum at the beginning of the small-angle scattering curves corresponds to the distance d _m = 2π/h ₀ between the planes (here, h ₀ is the position of the maximum on the scale h). It is 74–76.9 ? for solutions, 60 ? for gels, and 99 ? for polymer matrices with concentrations of up to 0.15% and 77 ? for those with the concentrations exceeding 0.15%, which is close to the estimation of the sizes of separate CdSe QDs that was obtained from the distribution histograms (60–80 ?). This result shows that CdSe/CdS QDs introduced in the polymer matrices disperse to form either separate particles or small aggregates and located at a distance on the order of 80 ? from each other.     

Synthesis,characterization, conductivity and sensor application study of polypyrrole/silver doped nickel oxide nanocomposites

Conducting polymer composites of polypyrrole (PPy) and silver doped nickel oxide (Ag-NiO) nanocomposites were synthesised by in situ polymerisation of pyrrole with different contents of Ag-NiO nanoparticles. The formation of nanocomposites were studied by Fourier transform infrared (FTIR) and UV–vis spectroscopy, field emission scanning electron microscopy (FE-SEM), X-ray diffraction (XRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and AC and DC conductivity measurements. The sensitivity of ammonia gas through the nanocomposite was analysed with respect to different contents of nanoparticles. Spectroscopic studies showed the shift in the absorption bands of polymer nanocomposite than that of pure PPy indicating the strong interaction between the nanoparticles and polymer chain. FESEM revealed the uniform dispersion of nanoparticles with spherically shaped metal oxide particles in PPy matrix. The XRD pattern indicated a decrease in amorphous domain of PPy with increase in loading of nanoparticles. The higher thermal stability and glass transition temperature of polymer nanocomposites than that of pure PPy were revealed from the TGA and DSC respectively. The dielectric properties, DC and AC conductivity of nanocomposites were much higher than PPy and these electrical properties increases with the loading of nanoparticles. The nanocomposites showed an enhancement in sensitivity towards ammonia gas detection than PPy.     

Effect of the degree of crosslinking on the interfacial layer structure of poly(vinyl chloride) dispersed with crosslinked poly(n-butyl methacrylate) particles

The interfacial layer structure of a model incompatible polymer blend system was analyzed using ¹H pulse nuclear magnetic resonance (pulse NMR) spectroscopy. Non-crosslinked and crosslinked poly(n-butyl methacrylate) particles with a mean size of ca. 0.9 μm were prepared by seeded emulsion polymerization, and the degree of crosslinking was varied. The particles were powdered using a freeze-dry method and dispersed in poly(vinyl chloride) by melt blending. Dynamic mechanical analysis indicated that the non-crosslinked particles were completely compatible. In contrast, mutual diffusion of the polymer chains in the crosslinked particles was restricted within the particle/matrix interfacial layer. As a result, an incompatible phase structure in which the crosslinked particles were dispersed in the continuous phase was formed. Pulse NMR analysis indicated that the interfacial layer thickness was in the range of 17–98 nm. The thickness decreased with an increase in the degree of crosslinking in the particles. The interfacial layer thickness in the particles was approximately 10 times larger than that for the incompatible polymer pair. Tensile test results indicated that the elongation at break was dependent on the thickness of the interfacial layer. The yield stress was developed for the particles with high hardness that was independent of the interfacial thickness.     

Influence of the nematic order on the rheology and conformation of stretched comb-like liquid crystalline polymers

We have studied the rheology and the conformation of stretched comb-like liquid-crystalline polymers. Both the influence of the comb-like structure and the specific effect of the nematic interaction on the dynamics are investigated. For this purpose, two isomers of a comb-like polymetacrylate polymer, of well-defined molecular weights, were synthesized: one displays a nematic phase over a wide range of temperature, the other one has only an isotropic phase. Even with high degrees of polymerization N, between 40 and 1000, the polymer chains studied were not entangled. The stress-strain curves during the stretching and relaxation processes show differences between the isotropic and nematic comb-like polymers. They suggest that, in the nematic phase, the chain dynamics is more cooperative than for a usual linear polymer. Small-angle neutron scattering has been used in order to determine the evolution of the chain conformation after stretching, as a function of the duration of relaxation t _r. The conformation can be described with two parameters only: , the global deformation of the polymer chain, and p, the number of statistical units of locally relaxed sub-chains. For the comb-like polymer, the chain deformation is pseudo-affine: is always smaller than (the deformation ratio of the whole sample). In the isotropic phase, has a constant value, while pincreases as tr. This latter behavior is not that expected for non-entangled chains, in which p varies as t _r ^1/2 (Rouse model). In the nematic phase, decreases as a stretched exponential function of t _r, while p remains constant. The dynamics of the comb-like polymers is discussed in terms of living clusters from which junctions are produced by interactions between side chains. The nematic interaction increases the lifetime of these junctions and, strikingly, the relaxation is the same at all scales of the whole polymer chain. Received 5 May 1999 and Received in final form 18 October 1999     

Frequency and temperature amplitude dependence of complex heat capacity in the melting region of polymers

Amplitude and frequency dependence of reversible melting of polycaprolactone (PCL) and an ethylene octene copolymer (EOM) were studied using temperature-modulated differential scanning calorimetry (TMDSC) (2?10^?1 Hz <f < 0.05 Hz) and shear spectroscopy (dynamic mechanical analysis, DMA) (5?10^?4 Hz < f < 100 Hz). It was found that the excess heat capacity of PCL is constant for temperature amplitudes in the range 5 mK < A_T < 2 K. The excess heat capacity decreases with frequency of temperature perturbation and tends to zero at about 0.1 Hz and 100 Hz for PCL and EOM, respectively. The constant excess heat capacity and the frequency dependence support the idea that reversible melting is related to a relaxation process on the surface of the polymer crystals. The occurrence of such a relaxation process was shown by shear modulus measurements in the same frequency and temperature region. The relaxation process is, in the melting region, much slower than main relaxation (glass transition). At low temperatures, a crossover can be seen, indicating the independence of both processes because of spatial separation. The main relaxation is related to the melt, while the other is related to the crystal surface.     

Combinatorial study of nanoparticle dispersion in surface-grafted macromolecular gradients

Surface-tethered assemblies of polymers with gradually varying molecular weight (MW) and/or grafting density are utilized to control the dispersion of nanosized particles. Using several case studies we show that these gradient polymer specimens represent ideal systems for combinatorial exploration of the parameters that control the distribution of the particles in surface-grafted layers. We demonstrate that the particle distribution is governed by the interplay between the particle size and the grafting density and molecular weight of the polymer brush.     

Analysis of ionic fragments from 308 nm photoablation of polyimide

The ionic products from excimer laser photoablation (=308 nm) of polyimide (Kapton) film have been studied as a function of fluence. Large ion masses up to about 900a.m.u. are easily observed, the mass distribution depending strongly on the fluence. Velocities of the emitted particles lie between 1400 and 10 000 ms^–1, again dependent on the fluence. A mechanism to explain the high velocities is suggested consisting of ionisation of the surface polymer molecules followed by a Coulomb explosion combined with expansion of the high density gas formed by the photoablation.     

Structure of filled linear polyethylene

The structure of linear polyethylene filled with various solid particles (glass beads, silica, kaolin) was examined by using scanning electron microscopy. The mode of attachment of filler particles to semicrystalline polymer was of particular interest. The filler particles were bonded to polymer by polyethylene fibrillar links whose number depended upon the properties of the filler.     

Electrodeposited metals at conducting polymer electrodes: I—Effect of particle size and film thickness on electrochemical response

Conducting polymers are electrochemically polymerized at platinum electrode substrates. The thickness, porosity and surface morphology of the resulting films are controlled by the charge passing during electropolymerization step and the synthesis conditions. The polymer films are modified by electrochemically depositing platinum particles. The technique of deposition depends on applying a programmed potential pulse at the polymer film from a solution containing platinum complex that resulted in the formation of platinum particles of controlled size and distribution. The effect of changing the size of platinum particles and polymer film thickness on the voltammetric behavior of the resulting hybrid material showed noticeable changes in the electro-catalytic current in acid medium. On the other hand, the electrochemical impedance spectroscopy experiments showed that diffusion and charge-transfer rate increased in the order: unmodified polymer films, thin polymer films containing small size/amount of platinum particles and relatively thick polymer films containing larger size/amount of platinum particles. The morphology of polymer films, size and distribution of platinum particles in the film were studied by scanning electron microscopy. The presence of platinum and its distribution over the film surface was confirmed from the X-ray dispersive analysis and surface mapping. The hybrid materials are good candidates for the application in devices for exchange of hydrogen ions.     

Preparation and surface encapsulation of hollow TiO nanoparticles for electrophoretic displays

Hollow black TiO nanosparticles were obtained via deposition of inorganic coating on the surface of hollow core-shell polymer latex with Ti(OBu)₄ as precursor and subsequent calcination in ammonia gas. Hollow TiO particles were characterized by scanning electron microscope, transmission electronic microscopy, X-ray diffraction, and thermogravimetric analysis. Encapsulation of TiO via dispersion polymerization was promoved by pretreating the pigments with 3-(trimethoxysilyl) propyl methacrylate, making it possible to prepare hollow TiO-polymer particles. When St and DVB were used as polymerization monomer, hollow TiO-polymer core-shell particles came into being via dispersion polymerization, and the lipophilic degree is 28.57%. Glutin-arabic gum microcapsules containing TiO-polymer particles electrophoretic liquid were prepared using via complex coacervation. It was founded that hollow TiO-polymer particles had enough electrophoretic mobility after coating with polymer.