Therapeutic biologics such as genes, peptides, proteins, virus and cells provide clinical benefits and are becoming increasingly important tools in respiratory medicine. Pulmonary delivery of therapeutic biologics enables the potential for safe and effective treatment option for respiratory diseases due to high bioavailability while minimizing absorption into the systemic circulation, reducing off-target toxicity to other organs. Development of inhalable powder formulation requires stabilization of complex biological materials, and each type of biologics may present unique challenges and require different formulation strategy combined with manufacture process to ensure biological and physical stabilities during production and over shelf-life. This review examines key formulation strategies for stabilizing proteins, nucleic acids, virus (bacteriophages) and bacterial cells in inhalable powders. It also covers characterization methods used to assess physicochemical properties and aerosol performance of the powders, biological activity and structural integrity of the biologics, and chemical analysis at the nanoscale. Furthermore, the review includes manufacture technologies which are based on lyophilization and spray-drying as they have been applied to manufacture Food and Drug Administration (FDA)-approved protein powders. In perspective, formulation and manufacture of inhalable powders for biologic are highly challenging but attainable. The key requirements are the stability of both the biologics and the powder, along with the powder dispersibility. The formulation to be developed depends on the manufacture process as it will subject the biologics to different stresses (temperature, mechanical and chemical) which could lead to degradation by different pathways. Stabilizing excipients coupled with the suitable choice of process can alleviate the stability issues of inhaled powders of biologics.
Keywords: Biologics; Formulation; Inhalation therapy; Powder.
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