Laila J. Jallo

Improvement of flow and bulk density of pharmaceutical powders using surface modification.

Improvement in flow and bulk density, the two most important properties that determine the ease with which pharmaceutical powders can be handled, stored and processed, is done through surface modification. A limited design of experiment was conducted to establish a standardized dry coating procedure that limits the extent of powder attrition, while providing the most consistent improvement in angle of repose (AOR). The magnetically assisted impaction coating (MAIC) was considered as a model dry-coater for pharmaceutical powders; ibuprofen, acetaminophen, and ascorbic acid. Dry coated drug powders were characterized by AOR, particle size as a function of dispersion pressure, particle size distribution, conditioned bulk density (CBD), Carr index (CI), flow function coefficient (FFC), cohesion coefficient using different instruments, including a shear cell in the Freeman FT4 powder rheometer, and Hansen flowability index. Substantial improvement was observed in all the measured properties after dry coating relative to the uncoated powders, such that each powder moved from a poorer to a better flow classification and showed improved dispersion. The material intrinsic property such as cohesion, plotted as a function of particle size, gave a trend similar to those of bulk flow properties, AOR and CI. Property improvement is also illustrated in a phase map of inverse cohesion (or FFC) as a function of bulk density, which also indicated a significant positive shift due to dry coating. It is hoped that such phase maps are useful in manufacturing decisions regarding the need for dry coating, which will allow moving from wet granulation to roller compaction or to direct compression based formulations.

Prediction of inter-particle adhesion force from surface energy and surface roughness

Fine powder flow is a topic of great interest to industry, in particular for the pharmaceutical industry; a major concern being their poor flow behavior due to high cohesion. In this study, cohesion reduction, produced via surface modification, at the particle scale as well as bulk scale is addressed. The adhesion force model of Derjaguin–Muller–Toporov (DMT) was utilized to quantify the inter-particle adhesion force of both pure and surface modified fine aluminum powders (∼8 μm in size). Inverse Gas Chromatography (IGC) was utilized for the determination of surface energy of the samples, and Atomic Force Microscopy (AFM) was utilized to evaluate surface roughness of the powders. Surface modification of the original aluminum powders was done for the purpose of reduction in cohesiveness and improvement in flowability, employing either silane surface treatment or dry mechanical coating of nano-particles on the surface of original powders. For selected samples, the AFM was utilized for direct evaluation of the particle pull-off force. The results indicated that surface modification reduced the surface energy and altered the surface nano-roughness, resulting in drastic reduction of the inter-particle adhesion force. The particle bond number values were computed based on either the inter-particle adhesion force from the DMT model or the inter-particle pull-off force obtained from direct AFM measurements. Surface modification resulted in two to three fold reductions in the Bond number. In order to examine the influence of the particle scale property such as the Bond number on the bulk-scale flow characterization, Angle of Repose (AOR) measurements were done and showed good qualitative agreements with the Bond number and acid/base surface characteristics of the powders. The results indicate a promising method that may be used to predict flow behavior of original (cohesive) and surface modified (previously cohesive) powders utilizing very small samples, and that the surface modification can drastically improve the powder flow for industrially relevant materials.

Passivation of High-Surface-Energy Sites of Milled Ibuprofen Crystals via Dry Coating for Reduced Cohesion and Improved Flowability

Ibuprofen micronization with dry coating is investigated to examine its influence on passivation/stabilization of high-surface-energy sites and reduced cohesion. A fluid energy mill was used to micronize ibuprofen particles down to 5-28 μm with or without simultaneous nanosilica coating. Powder flow property and dispersibility were characterized using FT4 powder tester and Rodos/Helos laser diffraction particle sizer. Surface energy was characterized using a next generation inverse gas chromatography instrument. Uncoated micronized ibuprofen showed an increased Lifshitz-van der Waals (LW) dispersion component of surface energy with increasing milling intensity. In contrast, dry-coated milled powders showed a significant reduction in the LW component, whereas physical mixture of uncoated micronized ibuprofen and silica exhibited no reduction in surface energy, indicating that dry coating is necessary for the passivation of high-energy sites of ibuprofen created during micronization. Surface energy of pure micronized ibuprofen was highly heterogeneous, whereas dry-coated ibuprofen had greatly reduced heterogeneity. Micronization with dry coating also improved flowability and bulk density as compared with pure active pharmaceutical ingredient micronization without coating, or just blending with silica. Overall, dry coating leads to decreased cohesion and improved flowability because of reduced LW dispersive component of surface energy and creating nanoscale surface roughness.

Explaining Electrostatic Charging and Flow of Surface-Modified Acetaminophen Powders as a Function of Relative Humidity Through Surface Energetics☆

Powder flow involves particle-particle and particle-vessel contacts and separation resulting in electrostatic charging. This important phenomenon was studied for uncoated and dry-coated micronized acetaminophen (MAPAP) as a function of relative humidity. The main hypothesis is that by modifying powder surface energy via dry coating of MAPAP performed using magnetically assisted impaction coating, its charging tendency, flow can be controlled. The examination of the relationship between electrostatic charging, powder flow, and the surface energies of the powders revealed that an improvement in flow because of dry coating corresponded to a decrease in the charging of the particles. A general trend of reduction in both electrostatic charging and dispersive surface energy with dry coating and relative humidity were also observed, except that a divergent behavior was observed at higher relative humidities (≥55% RH). The uncoated powder was found to have strong electron acceptor characteristic as compared with the dry coated. The adhesion energy between the particles and the tubes used for the electrostatic charging qualitatively predicted the decreasing trend in electrostatic charging from plastic tubes to stainless steel. In summary, the surface energies of the powders and the vessel could explain the electrostatic charging behavior and charge reduction because of dry coating.

INFLUENCE OF DEAGGLOMERATION STATES OF CARBON NANOTUBES ON THE THERMAL AND MECHANICAL PROPERTIES OF CARBON NANOTUBE-REINFORCED POLYETHYLENE OXIDE

Composites of polyethylene oxide and carbon nanotubes were produced by first deagglomerating highly agglomerated multi-walled carbon nanotubes in water, using a high-intensity ultrasonic probe, and then mixing with a solution of the polymer using a high-speed mixer. The deagglomeration of the nanotubes was carried out at different amplitudes of the vibrating ultrasonic probe. Differential scanning calorimetry results show an increase in melting temperature with increase in amplitude of sonication. Also, tensile test results show improved mechanical properties, with increased degree of deagglomeration of the nanotubes. SEM images show that the extent of nanotubes dispersion in the polymer matrix correlates with the extent of deagglomeration.