Investigations in Formation and Properties of Spray-Dried Microparticles using Monodisperse Spray Drying

  • Author / Creator
    Wang, Zheng
  • The scaling up of monodisperse spray drying and the formation and properties of several spray-dried particle systems are investigated in this thesis. First, gallium focused ion beam milling was used to manufacture multi-orifice plates installed in a vibrating orifice atomizer in order to increase the production rate of the monodisperse spray drying. The dual-orifice plate achieved an average production rate of 23.8 ± 2.0 mg/hr for the model particles, allowing sufficient powder masses for microscopic and spectroscopic analysis, as well as particle fragility testing within a reasonable spray drying operation time. The monodispersity of the spray-dried particles using the dual-orifice plate was proved by an in-line aerodynamic particle sizer and scanning electron microscopy. These results demonstrate that multi-orifice plates are capable of increasing the powder production rate of monodisperse spray drying while maintaining the monodispersity of the spray-dried particles. Second, the crystallization kinetics of spray-dried leucine particles from a co-solvent system were investigated using the scaled-up monodisperse spray drying. Leucine was dissolved in a water-ethanol co-solvent at ratios of 0.25/0.75, 0.5/0.5 and 1/0 w/w, and spray dried at inlet temperatures of 20, 40 and 80 °C. Numerical models were used to determine the time available for crystallization, which is an important parameter for predicting the crystallization kinetics at different co-solvent ratios and drying temperatures. Increasing the time available for crystallization correlated qualitatively with larger crystal size, more porous structure and lower particle fragility. These results highlight the importance of controlling crystal size and particle morphology via solvent environment and drying temperature during particle design and manufacturing processes for desired product properties. Finally, various shell-forming excipients for dry powder dosage forms were investigated to maintain powder dispersibility when the powders are exposed to a high-humidity environment simulating an out-of-package scenario. Various combinations of trehalose with leucine, trileucine, or pullulan were selected as the candidate excipient systems and were compared with neat trehalose particles. Scaled-up monodisperse spray drying was used to produce sufficient powder masses for dispersibility testing. The powder dispersibility was characterized as the emitted dose from a dry powder inhaler. The results indicated that trehalose/leucine 70/30 w/w maintained the highest emitted dose of 90.3 ± 10% at a 60 L/min flow rate after 60 min exposure to 90% relative humidity and 25 °C compared with trehalose/pullulan 70/30 w/w and trehalose/trileucine 97/3 w/w, showing the superior protection of leucine against moisture. Further investigations under more challenging conditions at a 15 L/min flow rate on the trehalose/leucine system with various compositions (70/30, 80/20, 90/10 w/w) showed that higher leucine concentration generally provided better protection against moisture and maintained higher powder dispersibillity. Therefore, leucine may be considered an appropriate shell-forming excipient for dry powder dosage forms to maintain powder dispersibility against moisture during administration.

  • Subjects / Keywords
  • Graduation date
    Spring 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.