Designing a ‘Ready-to-Use’ powder formulation platform for the inhaled protein therapeutics

Abstract

New biologics development coupled with an emerging biosimilars manufacturing scene are poised to stimulate growth in the biotechnology industry. Parenteral delivery, currently the mainstay of therapy, is often associated with pain, infection risks, high costs and poor patient compliance. Hence, non-invasive routes are preferred. The oral route is limited by low bioavailability, while the pulmonary route has been advocated as an attractive non-invasive yet efficacious alternative that could be applied for both local and systemic therapies. The dry powder inhaler (DPI), being a stable, convenient and non-invasive delivery device, is increasingly being considered for biologics delivery. However, balancing the concurrent demands for optimal aerosolization, bioactivity and stability is often difficult, requiring considerable expertise and development times. This work has therefore utilized the Taguchi experimental design to innovatively scrutinize several equipment and formulation parameters, and to propose and develop a ‘Ready-to-Use’ powder formulation platform which could be used to minimize development times and be applied as a useful starting template for biologics DPI development. Via the application of a model protein (lysozyme) and the following template conditions: Nano Spray Dryer, trehalose at 20% w/w, NaCl at 5% w/w and l-leucine at 15–20% w/w, fine particle fractions (FPFs) and bioactivities as high as 68.3 ± 2.3% and 95.2 ± 5.0%, respectively, were readily obtained. It was found that optimal FPF and bioactivity was less dependent on the spray dryer type, and more reliant on the type and concentration of protective and lubricating excipients. The powders obtained through this platform, exhibited strong aerosolization-promoting features in their particles (e.g. surface corrugation, hollow cavities), had particles with d50 of ∼2.30 ± 0.04 μm and were also stable to moisture-induced transformations. Potentially, this platform could be a useful precursor formulation suited to a variety of inhaled biomolecules, with just minor adaptations required for niche demands/applications.