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Enhanced Fluidization of Nanopowders for Pharmaceutical Applications


Daniel Lepek, Trainee, with inter-university advisors R. Pfeffer, R. Dave, P. Armenante and B. Glasser, researched “Enhanced Fluidization of Nanopowders for Pharmaceutical Applications”. The flowability of nanopowders encompasses a tremendous area of applications for pharmaceutical processes and drug delivery. Nanopowders, which are powders consisting of nanoparticle agglomerates, have unique fluidization characteristics. Due to their small size, these powders can provide greater reactivity and controlled functionality. Fluidization is a widely used process in the pharmaceutical industry. Using this process, the flowability of these powders can be characterized for further usage in pharmaceutical systems. Besides this process, the flowability of powders is important for aerosol applications of drug delivery, such as inhalers. Previous work in nano-fluidization includes the use of external forces (magnetic field, acoustics, vibration) to improve the flow properties of nanopowders. One of the aspects of this work is to study the effect of particle and fluid properties, e.g. viscosity on the quality of nanofluidization. An in-depth study was conducted in which nitrogen and neon were used as fluidization gases during nanofluidization. The particles used in the work include silica (primary size, 12 nanometers) and titania (primary size, 21 nanometers). These two nanopowders exhibit different fluidization characteristics. Nitrogen and neon were used to study the effect of a change of on gas viscosity approximately by a factor of two. Several experimental techniques were employed in order to investigate the fluidized bed behavior: measurement of bed expansion, settling velocity, and laser-based planar imaging of the nanoparticle agglomerates. The experiments were conducted at NJIT and at the University of Seville in order to seek for reproducibility. A main result derived from these experiments is that the size of agglomerates in fluidization does not depend essentially on the type of gas used at ambient conditions as theoretically expected. On the other hand, it is seen that an increment in gas viscosity enhances bed expansion and delays the onset of bubbling, which is attributable to a decrease on the sizes of small gas bubbles in the uniform fluid-like regime. For the silica nanoparticles, a transition from uniform fluidization to elutriation with full suppression of bubbling was observed. For this system, the bed expands continuously as the gas velocity is increased, while the amount of elutriated particles increases, without saturation. For the gas-fluidization of denser and large nanoparticle systems, i.e. titania, the bed transisted to a bubbling fluidization state, which is delayed by the use of the higher viscosity neon. The fittings of bed expansion data to the modified Richardson-Zaki equation and laser-based planar imaging allowed s to estimate the average agglomerate sizes of the order of hundred of microns, with a wide distribution and more or less independent of gas viscosity. Previously, the effect of vibration and electric fields on the quality of nanofluidization has been studied by groups at NJIT and IIT as part of an NSF NIRT grant. In this work, the behavior of a fluidized bed of silica nanoparticles under the combined influence of externally applied vibrations and an electrostatic field were studied. It was observed that the application of these fields separately has opposite effects on bed expansion. On one hand, vertical vibrations enhance bed expansion as the vibration intensity is increased up to a critical value. On the other hand, an electrostatic field applied in the horizontal direction hinders bed expansion. In previous research papers, it has been suggested that the size of nanoparticle agglomerates could be affected either by vibration or by the action of the electric field. Based on the experimental bed expansion data, fits to the modified Richardson-Zaki law were obtained, showing that vertical vibration tends to decrease the average agglomerate size in agreement with previous research. This new work suggests that both vibration and electric field produce a significant perturbation to the flow of agglomerates in the fluidized bed. Vibration transmists a vertical motion to the agglomerates that enhances bed expansion until the vibration velocity becomes of the order of the expected rising velocity of macroscopic bubbles. At this critical point, bubble growth is stimulated by vibration. A horizontal electrostatic field produces a drift of the charged agglomerates towards the walls that give rise to fluidization heterogeneity and bed collapse. When both fields are simultaneously applied, these opposite effects can be practically compensated. Thus, a quasi-equilibrium state representative of conventional fluidization was obtained at high vibration intensities and electric field strengths. A new technique currently being explored is the use of supercritical fluids for fluidization-based processes. Not only can be fluidization of pharmaceutical nanopowders be explored under these conditions, but structured nano-composites can be formed using supercritical methods such as crystallization and rapid expansion while the particles are in a fluidized state. Current nanopowders being examined include silica, alumina, and titania, which are used in a variety of biological processes. We would like to apply our knowledge of nanoparticle fluidization characteristics to pharmaceutical powders presently being used in industry. It is by extending our nanofluidization knowledge into the pharmaceutical industry that we gain a better understanding on how to adapt the nano-scale fluidization properties of these powders to the desired drug-delivery needs of the pharmaceutical industry.

Address Goals

All of the work presented above addresses the NSF strategic goal of DISCOVERY. A variety of new and modified techniques are being explored to enhance the fluidizability of nanopowders. The first main work, the viscosity study, included major modifications to previous experimental techniques. Although a study of gas viscosity on the quality of micron particle gas-fluidization has been previously performed by the Seville group, nanofluidization was not considered prior to this work. This work represents a joint international collaborative effort in which the influence of gas viscosity on the fluidization of micrometric particles and nanoparticle agglomerates were studied. Both theoretical modeling and experimental techniques were applied in this study. The bed expansion data of the silica nanopowder was used and fitted to the modified Richardson-zaki equation to determine the average agglomerate size. This correlated well to the experimental laser-planar images obtained of the nanoparticle agglomerates at the surface of the fluidized bed. This correlation implies that the theoretical modeling and imaging techniques can be successfully used to study and estimate the size of fluidized nanoparticle agglomerates. In the combined vibration and electrostatic field work, the physical mechanisms which govern nanofluidization were further explored. Unlike in the previously reported studies, both the vibrational frequency and amplitude were modified to control the intensity. A critical value was obtained in which bubble formation is stimulated, which curtails the bed expansion. Previously, this has not been observed. Also, the use of both electrostatic fields and vertical vibration to control the quality and behavior of nanofluidization leads to a further understanding on how these external fields effect the homogeneity of the fluidized bed.

The secondary NSF strategic goal of this work is LEARNING. A unique aspect of this work is the joint collaboration between the New Jersey Institute of Technology and the University of Seville. Our group, the New Jersey Center for Engineered Particulates, in chemical engineering at NJIT has worked closely with the Electrohydrodynamics group in the Faculty of Physics in Seville. The work for the gas viscosity study was performed at both sites which further showed that the work can be reproducible and performed at different scales. The combined vibration and electrostatic field work was performed in Seville, Spain and also received some additional support from an NSF IREE grant. There are also future plans for collaboration that will continue in the next year. The work studied so far has been presented at three national conferences and has resulted in two publications. The NSF REU program at NJIT has also been involved with this work. Previously, an undergraduate student assisted in the collection of agglomerate images at the surface of the fluidized bed. In the upcoming summer, an undergraduate student will help with the supercritical aspect of the work. Thus, the work on this project cross international borders and the knowledge derived from this work, is cross-linked down to the undergraduate level. Some of this work has been presented in NSF IGERT seminars and in courses offered by the NJIT Department of Chemical Engineering.