Generation of Respirable Particles from Surfactant Suspensions and Viscous Solutions at High Dose Rates

Donovan B. Yeates, Xin Heng

To enable the delivery of high concentrations of aerosolized therapeutic agents at high payloads from viscous solutions or sols, aerosols were generated from surfactant and polyvinylpyrrolidone, PVP with SUPRAER®. These fluids were atomized and the water evaporated using warm dilution air and infrared radiation. The resultant dry aerosol was concentrated using a virtual impactor. The masses of aerosol collected on filters at the output were determined gravimetrically. Particle size distributions were measured with a Marple-Miller cascade impactor. Viscosities were measured with a capillary rheometer. Surface tensions were measured with a contact angle analyzer. Aerosols between 2.6 and 4 μm MMAD were generated from 10% PVP solutions and 9.33% surfactant suspensions (34 cP) at aerosolization rates between 0.5 and 3 ml/minute with a modest increase in particle size with aerosolization rate that was less evident when surfactant was aerosolized. Particle size increased with viscosity over the range of 4 to 39 cSt. When aerosolizing 10% 8 kDa PVP solutions, the output increased in proportion to the aerosolization rate with 193 mg/min being delivered at 64% efficiency. Outputs of 0.7 and 1.2 g were collected in 3.3 and 6.7 min, respectively. When 9.33% surfactant suspensions were aerosolized, up to163 mg/min was delivered at 59% efficiency. The surface tension of surfactant was not changed following aerosolization and resuspension. SUPRAER increases the viscosity range over which respirable aerosols can be generated at up to 3 mg/s opening up possibilities for new treatments for respiratory ailments with surfactant and large molecules.

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