Amorphous pullulan trehalose microparticle platform for respiratory delivery.

Spray drying biologics and small-molecule drugs can increase their thermal stability relative to liquid dosage forms and allow for widespread distribution to developing countries without cold chain infrastructure. In this study, pullulan trehalose powder is spray dried for inhalation. The powder is characterized in terms of manufacturability, physical stability, device compatibility, and aerosol performance. The manufacturability is demonstrated by reasonable spray drying yield and powder flowability. The powder has relatively low cohesiveness and high compressibility without semi-elastic deformation. Short-term physical stability for ambient temperature dry storage and 40 °C storage in commercial pressurized metered-dose inhaler propellants HFA 134a and HFA 227 is shown. A theoretical model predicts a high glass transition temperature near the surface of the microparticles where biologics are expected to reside. Emission from a commercial dry powder inhaler demonstrates high dispersibility, optimal size for inhalation, and adequate total lung dose, exceeding many commercial inhalation devices. The powder can be filled, stored, and actuated from a pressurized metered-dose inhaler without changes in particle morphology or solid phase. The pullulan trehalose platform thus appears promising for respiratory delivery.