Experimental and theoretical studies on the particle formation process of particles for the improvement of pulmonary drug delivery

• Author / Creator

  Baldelli, Alberto

• The formation of dry microparticles from evaporating solution droplets was investigated and analyzed. The particle formation involved the creation and production of spray dried microparticles used for the delivery of drugs to treat pulmonary diseases. Studies of particle formation were conducted using a monodisperse droplet chain, which was created using a piezoceramic dispenser with an inner diameter of 30 µm for all the cases analyzed. The initial droplets ranged from 70 to 100 µm, and the final dried microparticles ranged from 0.3 µm to 25 µm, a range relevant to pulmonary drug delivery. The distance between two consecutive droplets was recorded; from these parameters, the main properties of the particle formation process, such as density, mass, aerodynamic diameter, volume equivalent diameter and velocity, were obtained. Studies varied from crystallizing to non-crystallizing systems. For the first group, cellulose acetate butyrate (CAB) in acetone was chosen for its high molecular weight. Such a substance generates high Peclet numbers, a phenomenon previously not analyzed in a monodisperse droplet chain. Initial concentrations of 0.37 and 10 mg/ml were chosen. External temperatures of 30, 40, and 55 °C were selected. For crystallizing systems, the material chosen for particle formation studies was sodium nitrate (NaNO3). The reasons for this choice were the properties of NaNO3: its crystallinity, its chemical structure and its high solubility in water. The use of NaNO3 as a solute allowed investigations of the time for crystallization, data unobtainable in prior experimental approaches. Systematic investigations of particle formation in the NaNO3 system were conducted using an appropriate selection of independent variables and analytical techniques suitable to the evaluation of evaporation and particle properties,. The independent variables and levels were the concentrations of the initial solution, which ranged from 5×10-5 mg/ml to 5 mg/ml, and the temperature of the drying gas, which ranged from 25 to 150 °C. The properties of the final dried particles most closely analyzed were density, void fraction, shell thickness, morphology and surface roughness. The analysis of morphology and roughness were correlated with cohesion forces between two microparticles. Cohesion forces varied from 1 to 100 nN depending on size, roughness and asperities, and peak-to-peak distances of the microparticles. The microparticles selected ranged between 15 and 1 μm, in diameter, between 1710 and 1 nm in roughness, and between 7000 nm and 50 nm in asperities. The experimental results were compared with theoretical results in the literature and the Rabinovich model chosen as the best theoretical method of determining cohesion forces between two rough microparticles. A multicomponent particle formation process involved the formation of microparticles from more than one solute. The multicomponent particle formation has previously been poorly studied, despite its impact on the quality of respiratory drug delivery. Potassium nitrate (KNO3), chosen for its similarities in molecular weight and solubility, was added to the evaporation of NaNO3 droplets. Initial conditions of environmental temperatures of 50 and 100ºC, concentrations of 1 to 10 mg/ml, and molar percentages of NaNO3 and KNO3 of 30:70, 50:50, and 70:30 influenced the time to reach saturation and, therefore, the distribution of chemical components on the shell of the final dried microparticles. The influence of the time to reach saturation on the distribution of final dried microparticles was verified. The solute with a shorter time to reach saturation composed the surface of the shell of final dried microparticles.

• Subjects / Keywords

  • Spray drying
  • Time to reach saturation
  • Particle Engineering
  • Crystallization process
  • Piezoceramic dispenser

• Graduation date

  Fall 2016

• Type of Item

  Thesis

• Degree

  Doctor of Philosophy

• DOI

  https://doi.org/10.7939/R3028PQ3Q

• 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.