Near-critical fluid micronization of stabilized vaccines, antibiotics and anti-virals

Abstract

Fine powder preparations of vaccines hold promise in resolving many issues encountered in the transport and delivery of vaccines such as loss of potency during transport through the ‘cold chain’ and needle free delivery. We have demonstrated the efficacy of a new powder-generating technique, Carbon dioxide Assisted Nebulization with a Bubble Dryer ® (CAN-BD), for producing dry, active powders of vaccines and small molecule pharmaceuticals. A hepatitis B surface antigen (HBsAg) protein vaccine and a live-attenuated measles vaccine were stabilized in various formulations, then processed into fine powders by nebulizing and drying them at near ambient temperatures (50 °C). Full preservation of HBsAg ELISA activity was achieved for formulations containing sufficient amounts of stabilizing trehalose. The powders were stored for 43 days either at −20 °C or at +66 °C without loss of potency. Commercial live-attenuated virus measles vaccine was further stabilized by adding trehalose or sucrose to retain full potency through CAN-BD drying. Powders had a mass median aerodynamic diameter (MMAD) of 1.9 μm and respirable mass fraction of 94%. A formulation of the anti-viral zanamivir was micronized to give 73% respirable mass fraction and MMAD of 2.4 μm. The antibiotic rifampin was processed by CAN-BD to yield powder with an MMAD of 1.2 μm and 86% respirable mass fraction.