Pharmaceutical droplets formation and diagnostics techniques development

Abstract

Through an extensive review on drugs disposition in human respiratory system, it is established that for the sake of optimum drug delivery into the lungs, the droplet size should be in the range from 1 to 10 microns. Thus, the present research is to investigate the problems associated with generating spray droplets in such a range. The physical principle of droplet formation is reviewed in this study with the objective to establish a guideline of selection for the most feasible atomization technology to produce the asthma care product. Acoustic ultrasonic vibration atomization of liquid is chosen. In this thesis, its pros and cons are analyzed along with a theoretical description of the ultrasonic atomization principle. Four commercially available pharmaceutical nebulizer products are critically studied and experimentally tested, and details of their working principles and mechanisms are examined. The work is carried out in conjunction closely with Chiaphua Industries Limited in developing a nebulizer prototype. The various droplet diagnostics techniques are investigated with the objective to find out the most appropriate one for the long-term purpose of the nebulizer production. The following criteria are given: 1. The technique must be useful on site and inexpensive. 2. The technique must be robust but reliably accurate. Three possible approaches have been tested. The first is to use side-scattering holography with the objective to establish a laboratory system for benchmark testing. The second is to use a multiple angle Lorenz-Mie light scattering system with the aim to make it as an instrument deliverable to factory use. The third is to use a microscope to look at the spray particles as they are produced. A MATLAB-based pattern recognition algorithm is developed for particle distribution measurement. The ensemble average intensities of the scattered light at a variety of detection angles are measured, forming a pattern of intensity distribution. Based on this pattern, the functional relation between the droplet size distribution and the angular scattered light intensity distribution is established to calculate the average size and size distribution of the scattering particles in the testing zone. As the final result, a prototype has been developed and demonstrated to a potential buyer with measured size distribution.