Dry powder inhalers (DPIs) and pressurised metered dose inhalers (pMDIs) are devices used to deliver therapeutic agents to the lungs. Typically, inhaled active pharmaceutical ingredients (APIs) are electrically resistive materials and are prone to accumulating electrostatic charge. The build-up of charge on inhaled therapeutics has traditionally been viewed as a nuisance as it may result in problems such as weighing errors, agglomeration, adhesion to surfaces and poor flow. Energetic processing steps such as micronisation, blending, blister/capsule filling as well as fluidisation of the dose will result in a large number of particulate collisions which can result in charge transfer. Charge present on aerosol particles may also affect the in vivo performance by altering the inhaler delivery efficiency and promoting electrostatic precipitation within the lung. This study aimed to develop and assess repeatable and reliable methods of performing electrostatic measurements of particles for inhalation and to understand the relationship of charge with environmental relative humidity. A powder ladle was constructed to perform net charge measurements of inhalation grades of lactose and used to assess the extent of triboelectrification during low shear turbula blending. Results demonstrated the importance of the method of addition used to transfer a sample to a net charge measurement device. The electrical properties of DPI formulations were investigated using a Charge Decay Time Analyser. It was determined that both API concentration and relative humidity play an essential role in governing the extent to which a DPI formulation can become electrostatically charged and the subsequent rate of charge decay. Finally, the bipolar Next Generation Impactor (bp-NGI) was developed and assessed as a tool to measure the bipolar charge to mass ratios of therapeutic aerosol particles in order to address the unmet need of combining a bipolar charge measurement system with an industry standard aerosol particle size classifier.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:687333 |
| Date | January 2014 |
| Creators | Rowland, Martin |
| Contributors | Price, Robert |
| Publisher | University of Bath |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
Page generated in 0.0022 seconds