Development of dry powder inhalation for biological drug modalities

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dc.contributor.advisorWilliams III, Robert O., III, 1956-
dc.contributor.committeeMemberWatts, Alan B.
dc.contributor.committeeMemberSmyth, Hugh D.C.
dc.contributor.committeeMemberCui, Zhengrong
dc.contributor.committeeMemberGhosh, Debadyuti
dc.creatorZhang, Yajie
dc.creator.orcid0000-0001-5570-5436
dc.date.accessioned2022-08-23T00:43:34Z
dc.date.available2022-08-23T00:43:34Z
dc.date.created2020-05
dc.date.issued2020-05
dc.date.submittedMay 2020
dc.date.updated2022-08-23T00:43:36Z
dc.description.abstractDry powder inhalers (DPI) have been developed to topically deliver therapeutics to the lung. Generally, a particle size range of 1-5 µm is desirable for the lung deposition of drug aerosols. To date, several particle engineering technologies have been developed and successfully applied to micronize powders of small molecule drugs. However, particle size reduction is challenging for biological materials due to their ductile texture and susceptibility to stresses encountered during processing. In this dissertation, three biological drug modalities (i.e. peptide, protein, and bacteriophage), are micronized using different particle engineering technologies. Chapter One provides a review of formulations and delivery systems used in peptide therapeutic products. Chapter Two describes several stages in the development of an excipient-free peptide inhalation product, including pre-formulation, formulation and processing, stability testing, and animal studies. It was demonstrated that jet milling is effective in manufacturing a stable, excipient-free peptide inhalation powder for the treatment of pulmonary fibrosis. In Chapter Three, inhalable dornase alfa powder is formulated with various excipients and the formulations are processed using thin film freeze-drying (TFFD) technology. The excipient screening was performed by employing design of experiment (DoE). Formulations that were both inhalable and preserve the enzymic activity of the protein were found. In Chapter Four, a review of inactive ingredients used in solid bacteriophage formulations is presented. Finally, Chapter Five explores the feasibility of using TFFD to manufacture inhalable bacteriophage powders. It was proved that TFFD is a suitable technology to produce powders that have desirable properties, including preserved bioactivity of bacteriophage, inhalable size range, and other physical characteristics.
dc.description.departmentPharmaceutical Sciences
dc.format.mimetypeapplication/pdf
dc.identifier.urihttps://hdl.handle.net/2152/115340
dc.identifier.urihttp://dx.doi.org/10.26153/tsw/42240
dc.language.isoen
dc.subjectDry powder inhalation
dc.subjectBiological modalities
dc.subjectPeptide
dc.subjectProtein
dc.subjectPhage
dc.titleDevelopment of dry powder inhalation for biological drug modalities
dc.typeThesis
dc.type.materialtext
thesis.degree.departmentPharmaceutical Sciences
thesis.degree.disciplinePharmaceutical Sciences
thesis.degree.grantorThe University of Texas at Austin
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy

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