Defense Date


Document Type


Degree Name

Doctor of Philosophy


Pharmaceutical Sciences

First Advisor

Michael Hindle


The overall aim of this research project was to develop surfactant dry powder formulations and devices for efficient delivery of aerosol formulations to infants using the excipient enhanced growth (EEG) approach. Use of novel formulations and inline delivery devices would allow for more efficient treatment of infants suffering from neonatal respiratory distress syndrome and bronchiolitis.

A dry powder aerosol formulation has been developed using the commercial product, Survanta ® (beractant) and EEG technology to produce micrometer-sized hygroscopic particles. Spray drying and formulation parameters were initially determined with dipalmitoylphosphatidylcholine (DPPC, the dominant phospholipid in pulmonary surfactant), which produced primary particles 1 um in size with a mass median aerodynamic diameter of 1-2 um.

Investigation of dry powder dispersion enhancers and alcohol concentration on the effect of powder aerosol characteristics were performed with the Survanta-EEG formulation. The optimal formulation consisted of Survanta ® , mannitol and sodium chloride as hygroscopic excipients, and leucine as the dry powder dispersion enhancer, prepared in 20% v/v ethanol/water. The powders produced primary particles of 1 um with >50% of the particles less than 1 um. The presence of surfactant proteins and surface activity were demonstrated with the Survanta-EEG formulation following processing.

A novel containment unit dry powder inhaler (DPI) was designed for delivery of the surfactant-EEG formulation using a low volume of dispersion air. Studies explored optimization of air entrainment pathway, inlet hole pattern, delivery tube internal diameter and length. With 3- 10 mg fill masses of spray dried surfactant powder, the DPI enabled delivery of >2 mg using one 3-mL actuation of dispersion air. Overall, it was possible to deliver >85% of the loaded fill mass using three actuations.

Nebulized aerosol formulations are characterized with low delivered doses. Using a novel mixer-heater delivery system, the highest estimated percent lung dose achieved during realistic in vitro testing of a Survanta-EEG formulation aerosolized with a commercial mesh nebulizer was when nebulization was synchronized with inhalation of the breathing profile. Design changes to the mixer-heater system eliminated the need for synchronization, achieving an estimated percent lung dose of 31% of the nominal, an improvement compared with existing systems that achieve approximately <2% lung dose.


© Susan Boc

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