Electrostatic properties of formulation component materials and blends play an important role in dry powder inhalation (DPI) products, and that valid measurement of charge distribution will lead to more precise control of powder behavior in DPI manufacturing processes. Ultra-fine powders are known to be bipolarly charged, have non-spherical shapes and tend to be highly cohesive. Real time, non-invasive techniques need to be developed to obtain a precise and accurate time-history characteristic of electrically charged powders as they aerosolize from a DPI product, and how this measure relates to materials behavior throughout the various steps of a manufacturing process i.e. from drug micronisation, blending with lactose, through to filling dose units. A novel non-invasive technique for simultaneous measurement of size and charge of pharmaceutical powders is considered which employs the Phase Doppler Anemometry (PDA) system. Previous research demonstrated the advantages of this technique in measuring the bipolar charge distribution on a population of particles. These findings led to significant improvements in understanding performance of dry powder formulations, manufacturing processes and development of new platforms for inhaled drug delivery. The main aim of this research is to perform an investigation of electrostatic propertiesof pharmaceutical dry aerosols using the PDA system. The PDA technique was used to track the motion of charged particles in the presence of an electric field. The magnitude as well as the polarity of the particle charge can be obtained by solving the equation of particle motion in DC and AC fields combined with the simultaneous measurement of its size and velocity. The results show the capability of the technique to allow real-time size and charge distribution in the control of dry powder attributes that are critical to fully understanding manufacturing design space. The data obtained from initial investigations of electrical properties of pharmaceutical powders and bipolar charge measurements was used to perform an in-depth study of electrostatic properties of pharmaceutical aerosols dispensed by dry powder inhaler (DPI) devices. The delivery of a drug to the lungs can only be achieved by a combination of inhaler device and drug formulation which is capable of producing an aerosol of an aerodynamic diameter smaller than 5 μm and of appropriate charge. The aerosols generated by these devices are often bipolarly charged and can influence specific site deposition in human lung. By controlling the electrostatic charge generated by tribielectrification, it may be possible to achieve the desired drug deposition in the airways. Bipolary charged dispensed ultrafine particles are inhaled through the extrathoracic and tracheobronchial airways down into the alveolar region. Anatomically realistic respiratory airways and computation fluid dynamics (CFD) models have been created to study airflow structures and predict aerosol deposition within the human respiratory system using visible human data sets, human casts and morphometric data. Many theoretical studies of charged aerosol deposition in human respiratory systems have been developed, however getting real time, non-intrusive data of bipolar charge levels on aerosols dispensed from DPI’s within the human respiratory system represents a challenging issue. This research project presents a simplified human upper airway model which combined with the modified Phase Doppler Anemometry (PDA) system is able to provide real time bipolar charge distributions of aerosols delivered from several commercially available DPI devices. A three dimensional (3D) reconstruction of the upper respiratory system was performed from two dimensional (2D) images obtained from computerized tomography (CT), magnetic resonance imaging (MRI) and cryosectioned images available from Visible Human Server data set (Ecole Polytechnique Fédérale de Lausanne). The resulting dimensions of the model were consistent with morphometric data from the literature from which the simplified upper airway model consisting of two connected segments, i.e., the oral airways from the mouth to trachea (Generation G0), was created. The findings of this study provided a better understanding of the interaction between specific active ingredients and DPI devices. These results may be used in designing future generation DPI devices and a better understanding of aerosol transport and deposition efficiency within the human airways.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:665822 |
| Date | January 2012 |
| Creators | Beleca, Radu |
| Contributors | Balachandran, W.; Abbod, M. |
| Publisher | Brunel University |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://bura.brunel.ac.uk/handle/2438/11271 |
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