(240d) Advances in Spray Freeze-Drying for Uniform Spherical Bulk Intermediate Product

Atmospheric spray freezing and rotational dynamic vacuum freeze drying is a new technology that is now being introduced for pharmaceutical aseptic processing of parenteral products. This process, which is designed to improve on traditional lyophilization techniques produces microspheres which can be held as bulk material and filled on demand into primary packages and devices. The spheres may be formed in a selectable size range from 300 – 1000 µm.

The freeze-dried spheres are homogeneous, free flowing and dust free. This physical form allows for significantly increased flexibility in the supply chain, either by the improved stability and handling of a free flowing solid for transporting bulk active, or by dosing and batch size flexibility when filling finished product. Producing a combination product becomes as simple as filling the necessary types of spheres into the primary packaging. Devices as well as vials may be filled, opening the possibility of new product types.

Further product innovation is possible due to the range of capability of the technique. Higher concentration formulations are suitable to process, while still offering fast reconstitution properties. The additional concentration may enable subcutaneous administration. The concept also allows for new formulation strategies by opening the range of solid dosage form technologies like coating and multiparticulate dosage forms for freeze dried products.

The process is performed in a fully contained process line which includes the generation of frozen micropellets and a dynamic rotary freeze drying process. This arrangement greatly increases the surface area available for heat and mass transfer leading to process efficiencies.