Spray-freeze-drying in the manufacture of pharmaceuticals
Over the last decade, the development of new drug delivery methods and devices for dry powder inhalation1, needle-free intradermal powder injection2 or sustained parenteral drug delivery3 has led to an increasing demand for powder formulations incorporating an active pharmaceutical ingredient (API)4,5.
In contrast to the production and handling of powders for oral dosage forms, methods to prepare stable biopharmaceutical powders are limited due to the sensitivity of peptides and proteins to powder processing conditions4,6. Furthermore, bulk properties such as size distribution or density of the final particles are different depending on the application4,5,7. Particles for dry powder inhalation, for example, should have particles of less than 5 µm in diameter and a narrow size distribution5, whereas particles for needle-free ballistic injection must be 30-60µm with a density greater than 0.7 g/ml7 for a successful intradermal delivery. One of the most commonly used methods of drying protein formulations is freeze-drying8-11 but, because it does not involve droplet formulation, the final dry cake can only be reduced to particles by subsequent mechanical milling or grinding4. Some reported disadvantages associated with this method of powder manufacturing include the following:
Production of particles with diameters above 1 mm
Broad particle size distributions
Changes of solid state and degradation of the peptide or protein due to heat generation during inter-particle collision12,13