Powder suspensions in non-aqueous vehicles for delivery of therapeutic proteins.

Formulating biopharmaceuticals is a challenging task due to their complex and sensitive nature. Protein drugs are typically marketed either as an aqueous solution or as a lyophilizate. Usually aqueous solutions are preferred as neither drying nor reconstitution are required. But it may be unfeasible if the protein features low stability. An interesting alternative to avoid at least reconstitution are protein powder suspensions in non-aqueous vehicles. Such formulations combine the ready-to-use approach with the high protein stability in the solid state. Additionally, protein powder suspensions offer a potentially lower viscosity compared to aqueous solutions at high protein concentrations. Besides injection, other application routes might also benefit from the protein powder approach such as topical or inhalational delivery. Protein powders, which can be dispersed in the non-aqueous suspension vehicle, are usually prepared by spray-drying or freeze-drying with an additional milling step, but other techniques have also been described in literature. An ideal powder preparation technique results in minimum protein damage and yields particle sizes in the lower micrometre range and homogeneous particle size distribution enabling subcutaneous or intramuscular injection through hypodermic needles. As suspension vehicles traditional non-aqueous injectable liquids, such as plant oils, may be selected. But they show an inherent high viscosity, which can lead to unacceptable glide forces during injection. Furthermore, the vehicle should provide high product stability with respect to protein integrity and suspension resuspendability. This review will describe how proteins can be formulated as protein powder suspensions in non-aqueous vehicles for subcutaneous injection including potential vehicles, protein powder preparation techniques, protein and suspension physical stability, as well as the use in the field of high concentration protein formulations.