Antoine Ghanem

Nanocrystals: comparison of the size reduction effectiveness of a novel combinative method with conventional top-down approaches.

Nanosizing is a non-specific approach to improve the oral bioavailability of poorly soluble drugs. The decreased particle size of these compounds results in an increase in surface area. The outcome is an increased rate of dissolution, which can lead to a better oral absorption. Standard approaches are bottom-up and top-down techniques. Combinative technologies are relatively new approaches, and they can be described as a combination of a bottom-up process followed by a top-down step. The work presented in this paper can be described as a combination of a non-aqueous freeze drying step (bottom-up), followed by wet ball milling or high pressure homogenization (top-down) to produce fine drug nanocrystals. The crystal habit of the model drug glibenclamide was modified by freeze drying from dimethyl sulfoxide (DMSO)/tert-butanol (TBA) solvent mixtures using different ratios. The resulting drug powders were characterized by scanning electron microscopy (SEM) as well as by X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC). It was shown that the combinative approach can significantly improve the particle size reduction effectiveness of both top-down methods over conventional approaches. Drug lyophilization using DMSO:TBA in 25:75 and 10:90 v/v ratios resulted in a highly porous and breakable material. The milling time to achieve nanosuspensions was reduced from 24h with the jet-milled glibenclamide to only 1h with the modified starting material. The number of homogenization cycles was decreased from 20 with unmodified API to only 5 with the modified drug. The smallest particle size, achieved on modified samples, was 160nm by wet ball milling after 24h and 355nm by high pressure homogenization after 20 homogenization cycles at 1500bar.

Micromechanisms of slow crack growth in polyethylene under constant tensile loading

Abstract Circumferentially notched specimens of a first generation and a third generation pipe-grade of high density polyethylene with similar weight average molar masses have been subjected to constant tensile loads at 80°C. A transition from full ligament yielding to failure by stable sub-critical crack growth was observed as the applied load was decreased. The specimen lifetimes in this latter regime were dependent on the initial stress intensity factor, Ki, and failure was associated with slow crack propagation preceded by formation of a wedge-shaped cavitational deformation zone at the notch tip. The fibril diameters in the deformation zones decreased with stress intensity factor near the transition, the limiting behaviour of a relatively slow crack growth resistant third generation grade at the lowest Ki being inferred from testing in Igepal™ to be the breakdown of diffuse zones of interlamellar voiding. This regime was not directly accessible to testing in air within the allotted experimental times. However, comparison with the results of accelerated testing in cyclic fatigue has indicated stable interlamellar voiding in the third generation grade not to necessitate the presence of Igepal. Moreover, in both grades, very similar modes of deformation were observed in air and in Igepal at relatively high Ki. Igepal was therefore inferred not to lead to qualitative changes in the range of mechanisms that are characteristic of slow crack growth in polyethylene.

Morphology of extruded high-density polyethylene pipes studied by atomic force microscopy

Atomic force microscopy (AFM) was used to study the structure of extruded polyethylene (PE) pipe. During extrusion, the outer surface of the pipe was cooled with water. Two cross sections, parallel and transverse to the extrusion direction, were examined in order to spatially follow the structural development during extrusion. The morphology revealed was spherulitic, and the spherulites had a mostly banded appearance when viewed under the AFM. We were not able to distinguish an oriented skin layer at the surface of the pipe, either by AFM or polarizing microscopy. The changes in the pipes structure resulting from the cooling conditions were found to be rather gradual, and no clearly defined zones were observed. A slight orientation towards the extrusion direction was detected only in the area of the pipe crystallized under the lowest degree of undercooling. Measured spherulitic size, band period, and lamellae thickness showed a gradual increase in their values from the cooled to the noncooled surface of the pipe. Transmission electron microscopy (TEM) was used to verify the band period and lamellae thickness measurements done by AFM.

Influence of EP/PP viscosity ratio on the surface morphology and elasticity of injection moulded PP/EP

The influence of the viscosity ratio between (ethylene-propylene) copolymer (EP) and polypropylene (PP) on the EP surface distribution in injection moulded disks of PP/EP resins has been investigated by transmission electron microscopy (TEM) and by atomic force and force modulation microscopies (AFM and FMM). TEM images taken on transverse sections parallel to the injection direction reveal that, for high EP/PP viscosity ratios, large (>1 mu m) undeformed EP nodules are observed up to the surface. The AFM and FMM observations performed on the surface reveal soft regions of the same size embedded in a more rigid matrix (undeformed EP nodules present at or just below the surface). For low viscosity ratios, EP rubber nodules, strongly elongated parallel to the surface, are observed by TEM. From FMM measurements, the elastic modulus is found to be homogeneous across the surface and is comparable to that measured above EP nodules on the high viscosity ratio resin

Reliable nanomaterial classification of powders using the volume-specific surface area method

AbstractThe volume-specific surface area (VSSA) of a particulate material is one of two apparently very different metrics recommended by the European Commission for a definition of “nanomaterial” for regulatory purposes: specifically, the VSSA metric may classify nanomaterials and non-nanomaterials differently than the median size in number metrics, depending on the chemical composition, size, polydispersity, shape, porosity, and aggregation of the particles in the powder. Here we evaluate the extent of agreement between classification by electron microscopy (EM) and classification by VSSA on a large set of diverse particulate substances that represent all the anticipated challenges except mixtures of different substances. EM and VSSA are determined in multiple labs to assess also the level of reproducibility. Based on the results obtained on highly characterized benchmark materials from the NanoDefine EU FP7 project, we derive a tiered screening strategy for the purpose of implementing the definition of nanomaterials. We finally apply the screening strategy to further industrial materials, which were classified correctly and left only borderline cases for EM. On platelet-shaped nanomaterials, VSSA is essential to prevent false-negative classification by EM. On porous materials, approaches involving extended adsorption isotherms prevent false positive classification by VSSA. We find no false negatives by VSSA, neither in Tier 1 nor in Tier 2, despite real-world industrial polydispersity and diverse composition, shape, and coatings. The VSSA screening strategy is recommended for inclusion in a technical guidance for the implementation of the definition. Graphical abstractWe evaluate the extent of agreement between classification by electron microscopy (EM) and classification by Volume-Specific Surface Area (VSSA) on a large set of diverse particulate substances. These represent the challenges anticipated for identification of nanomaterials by the European Commission recommendation for a definition of nanomaterials for regulatory purposes.

On the validity of crystallization kinetics parameters derived from the depolarized light intensity (DLI) technique : An experimental study of polyvinylidene fluoride

Although the depolarized light intensity technique has been known for some decades, the time dependence of light intensity does not yet seem to be well understood. In this article, devoted to the crystallization kinetics of polyvinylidene fluoride (PVDF), we present some of the problems associated with quantitative analysis. Parameters such as incident light intensity-in combination with the detection system-and specimen thickness are shown to dramatically affect the apparent kinetics. Experiments on single spherulites grown in very thin films can help interpret the intensity-time curve. Our results demonstrate that care should be taken when comparison is made between DLI and differential scanning calorimetry.