Optimizing the design and dosing of dry powder inhaler formulations of the cationic liposome adjuvant CAF®01 for pulmonary immunization

Thermostability is one of the product characteristics preferred by WHO for vaccines against respiratory infections due to ease administration, pain minimization, and low costs. Thermostable dry powder inhaler (DPI) vaccine formulations can induce protective antibodies T cells at site infection in lungs. However, majority licensed human based on liquid dosage forms, there no mucosal adjuvants. The cationic adjuvant formulation 01 (CAF®01) a liposome-based system that (i) induces robust antibodies, (ii) safe well-tolerated clinical trials, (iii) immune responses after pulmonary administration. optimal DPI CAF®01 immunization are not known. Here, we show spray-dried with combination sugars amino acid leucine exhibit aerosolization properties distribute lung lobes upon We demonstrate type amorphous sugar used as stabilizer amount (w/w) during spray drying affect physicochemical aerosol performance formulations. By systematically varying ratios trehalose, dextran excipients drying, manufactured displayed spherical or wrinkled surface morphology, an aerodynamic diameter particle size distribution deep deposition, solid-state suitable delivery. Using design-of-experiments-based approach, identified most process parameters vivo generator, i.e. , PreciseInhale® system, which was measure flowability aerosols. found trehalose (70% w/w) (30% physicochemical, morphological, solid-state, deposition. Upon this distributed way almost identical biodistribution non-spray dried formulation. Hence, CAF®01, prepared matrix shell, display inhalation.