PulmoCraft™ a manufacturing solution for DPI dosage forms.
For successful pulmonary delivery of dry powder inhaled (DPI) formulations, the production of small particles with an aerodynamic particle size between 1-5 μm is required to reach the deep lung. There are a number of techniques that can be used to achieve this size range with spray drying being seen as a manufacturing method capable of producing spherical particles with excellent control of size, morphology and aerosolisation behaviour.
Creating particles for optimum pulmonary delivery can be achieved by careful selection of both the formulation, solution and spray drying parameters. For example, criteria such as feedstock concentration, atomisation pressure and drying temperature all impact on particle morphology and ultimately aerodynamic properties.
One major challenge that occurs during this development phase is one of collection and subsequently process yield. In short, small particles can be produced relatively easily using a standard spray dryer but collection becomes increasingly difficult as the particle size drops below 5 μm. Upperton has devised a two-step manufacturing process called PulmoCraft™ to overcome the scale-up issues associated with producing and collecting small particles.
The PulmoCraft™ Process
To overcome these scale-up pulmonary delivery challenges Upperton has developed a two-step solution to this problem; a combination of spray drying and dry powder milling that can be used to increase throughput and yield without deleteriously affecting product yield.
In the first step, larger spray dried particles are first produced on the spray drier with mean particle sizes above 5 µm (which are within the range required for efficient cyclone collection on these machines). These particles can then be reduced to the required size range using dry powder milling, generating particles in the desired 1-5 µm size range whilst maintaining good yields and processing rates.
Using this approach, feed concentration and processing rate can both be increased; significantly reducing both manufacturing time and cost. The spray dried particles are then reduced to the target particle size distribution, using a carefully controlled dry powder milling process. The result is a much faster, more efficient process producing large quantities of powders with excellent aerodynamic properties.
Cascade Impactor testing of our powders produced in this way confirms that it is possible to reproducibly generate dry powders with an aerodynamic particle size distribution of 1-5 µm, with fine particle fraction in excess of 70% when formulated powders are delivered from commercially available DPIs.