Enhanced engineered formulations in dry powder inhalers for high dose lung delivery
Susana Saldanha1, Luís Sousa2 & Eunice Costa1
1Inhalation and Advanced Drug Delivery, R&D, Hovione FarmaCiência SA, Lumiar, 1649-038, Portugal
2Analytical Development, R&D, Hovione FarmaCiência SA, Lumiar, 1649-038, Portugal
The work reports the development of an enhanced inhalable pharmaceutical formulation for high dose delivery to the lungs that comprises spray dried cohesive composite particles physically blended with fluidizing particles. Formulations were tested in combination with the larger version of the marketed TwinCaps© single-use dry powder inhaler: the TwinMax DPI (Hovione). Spray dried formulations are proven flexible platforms that can successfully deliver multiple active pharmaceutical ingredients, from small molecules to biologics, to the lung at relatively high dosages. However, optimized spray dried formulations are still challenging in terms of flow properties, requiring complex manufacturing processes and often the use of more complex devices, with multiple dispersion mechanisms, for successful aerosolization. Herein, an efficient aerodynamic performance of a model spray dried formulation is obtained by physically blending with an appropriate fluidizer, combining spray drying and blending, two unit operations, that are not usually combined. The testing in combination with a single-use reservoir-based device, with minimum complexity, shows that this formulation provides a solution for delivering highly cohesive powders, such as spray dried powders, to the lungs by increasing the FPFED from 9.8% to 49% when comparing with neat composite particles. The combination of the single-use device and the pharmaceutical composition embodies a dry powder inhaler platform that can be applied in a wide range of acute indications, more specifically in high drug load inhalable powders for respiratory intake.
The combination of composite particles with carrier particles provides enhanced dosing efficiency by improving aerodynamic performance relatively to neat spray dried particles, especially when using reservoir type devices such as TwinMax DPI.