Influence of Formulation Factors on the Aerosol Performance and Stability of Lysozyme Powders: a Systematic Approach
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With the growing interest in developing biologics for pulmonary delivery, systematic fast screening methods are needed for rapid development of formulations. Due to the labile nature of macromolecules, the development of stable, biologically active formulations with desired aerosol performance imposes several challenges both from a formulation and processing perspective. In this study, spray-freeze-drying was used to develop respirable protein powders. In order to systematically map the selected design space, lysozyme aqueous pre-formulations were prepared based on a constrained mixture design of experiment. The physicochemical properties of the resulting powders were characterized and the effects of formulation factors on aerosol performance and protein stability were systematically screened using a logic flow chart. Our results elucidated several relevant formulation attributes (density, total solid content, protein:sugars ratio) required to achieve a stable lysozyme powder with desirable characteristics for pulmonary delivery. A similar logical fast screening strategy could be used to delineate the appropriate design space for different types of proteins and guide the development of powders with pre-determined aerodynamic properties.
KEY WORDSdry powder biologics spray-freeze-drying pulmonary delivery dry powder inhaler
The authors are thankful to the members of Smyth lab (in particular to Dr. Matthew Herpin and Daniel Moraga), to Dr. Abbe Haser, and to the team at Amgen (in particular Nitin Anghan and Michael Schneider) for valuable feedbacks.
This work was supported by Amgen Inc.
Compliance with Ethical Standards
The terms of this arrangement have been reviewed and approved by the University of Texas at Austin in accordance with its policy on objectivity in research.
Conflict of Interest
The author (HDCS) of this paper consults for and has equity ownership in Respira Therapeutics and Nob Hill Therapeutics on inhaled product development. The other authors declare that they have no conflict of interest.
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