Safer Vaccines and Antibiotics Manufactured through Use of Near- Critical or Supercritical Fluids

Near-critical and supercritical fluids have been used successfully in the manufacture of vaccine, antibody and antibiotic microparticles by Carbon-dioxide Assisted Nebulization with a Bubble Dryer ® (CAN-BD). In CAN-BD two fluid streams, a drug, antibody, or vaccine solution or suspension, and supercritical or near-critical CO2, are intimately mixed in a low dead volume tee. These mixed fluid streams are then rapidly expanded through a flow restrictor to atmospheric pressure where the micro-bubbles and micro-droplets, formed in the plume, are dried by mixing with warm nitrogen at 50-65 C. The resulting free flowing stable microparticles, containing vaccine virus or drug particles imbedded in sugars, amino acids, and/or other excipients, are within a respirable size range (1-5 μm) and have less than 2% residual moisture. These powder properties are ideal for developing a needle-free delivery system that addresses the Grand Challenges in Global Health Initiative #3. In response to this challenge, we developed unit-dose packaging that preserves powder properties by protecting them from moisture, oxidants and UV exposure as well as a low cost “active” dry powder inhaler to disperse the Edmonston-Zagreb measles vaccine. This inhalable vaccine has demonstrated 2-year storage stability at 2-8 C, high virus titers, the ability to create a robust immune response and challenge protection in Rhesus macaques. Our continuing work includes CAN-BD anti-tuberculosis antibiotic microparticles for needle-free, combination tuberculosis therapy. Unit-dose dry powder vaccines and antibiotics have the potential to provide easy to use, stable products with improved safety profiles.