A Particle Engineering Approach to the Development of Microparticles Suitable for Enteric Delivery of Biologics

  • Author / Creator
    Karim, Shabab Bin
  • Despite tremendous advances in the field of medical science, enteric infections still account for millions of deaths globally each year. Inaccessibility to clean drinking water, sanitation systems and proper healthcare infrastructure in developing parts of the world remains a huge obstacle to mitigating the impact of these infections. The emergence of antibiotic-resistant strains of bacteria and the insufficient development of new small-molecule antibiotics with which to combat them call for the exploration of new avenues in the treatment of infectious enteritis and serve as the main motivation behind this work. Delivering bacteriophages to the enteric region to act against invading bacteria can be a viable treatment option, but the survival of the phages through the mechanical and environmental stresses of processing conditions and then through the hostile chemical conditions of the stomach is a major problem to resolve. Using spray drying to create bacteriophage-carrying microparticles with a stabilizing core and a shell capable of withstanding shifts in pH is a potential solution to these issues. This thesis details the implementation of a particle engineering approach to understanding the previously unexplored particle formation process of Eudragit-trehalose microparticles using an improved monodisperse droplet chain. It then evaluates the effectiveness of the particle shells using a new shadowgraphic technique.
    To gain a better understanding of the particle formation process, modifications were made to an existing monodisperse droplet chain instrument. Integrating interferometric laser imaging for droplet sizing into the instrument improved the reliability of initial droplet diameter measurement. The particle collection efficiency of the instrument was also improved by the addition of a custom-built single-nozzle impactor. Using the information gathered from the instrument, initial droplet diameter can be measured with less than 1% error. The density of particles collected from the instrument can also be measured, but the accuracy depends heavily on the morphology of the particle. For spherical, solid particles like trehalose, the average density of the particle can be measured with only a small margin of error (5% w/w Eudragit remained intact after one hour’s exposure at pH 2, a result that was verified by the Raman spectrum of the formulation cured from the acidic medium. The particles suspended in an alkaline medium showed slow dissolution, indicating the time-dependent release pattern of the spray-dried particles and therefore their suitability for enteric delivery of biologics.

  • Subjects / Keywords
  • Graduation date
    Fall 2021
  • Type of Item
  • Degree
    Master of Science
  • DOI
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.