{"id":{"repo_id":"cambridge","oai_identifier":"oai:www.repository.cam.ac.uk:1810/273209"},"canonical_url":"https://search.dev.ndltd.org/etd/cambridge/oai:www.repository.cam.ac.uk:1810/273209","repository":{"repo_id":"cambridge","name":"Cambridge University","base_url":"https://api.repository.cam.ac.uk/server/oai/request"},"display":{"title":"Investigating Controlled Release Pulmonary Drug Delivery Systems","abstract":"The therapeutic effect of pulmonary drug delivery systems is limited by its rapid clearance from the lungs by robust clearance mechanisms. By controlling the release of drugs, the therapeutic effect of pulmonary drug delivery systems, as well as patient convenience and compliance could be improved by reducing the number of times drugs need to be administered. In this study, two controlled pulmonary drug delivery systems for drugs of different solubilities were investigated and they were characterised for their viability as effective controlled release pulmonary drug delivery systems, particularly in areas of aerosol performance and dissolution profile. A hybrid protein-polymer controlled release pulmonary drug delivery system was developed to sustain the release of a water-soluble anti-asthma drug, cromolyn sodium (CS). Two excipients with complementary characteristics – a protein, bovine serum albumin, and a polymer, polyvinyl alcohol – were formulated together with CS via co-spray drying, with varying protein-polymer ratios and drug loadings. The hybrid particles showed promise in combining the positive attributes of each excipient, with respirable particles shown to sustain the release of CS with a fine particle fraction of 30%. Combining the two excipients was complex, with further optimisation of the hybrid formulations possible. A commercially available polymer, Soluplus® was spray-dried with a poorly-water soluble corticosteroid, beclomethasone dipropionate (BDP). The resultant respirable powders were shown to have potential for use as a controlled release pulmonary drug delivery system with up to 7-fold improvement in the amount of BDP released compared to spray-dried BDP. The spray-dried BDP-Soluplus® powders were found to be amorphous, and physically stable against re-crystallisation for up to 9 months at accelerated stress test conditions with drug loadings of up to 15 % (w/w). Although it provided a platform to compare between formulations, the USP 4 flow-through cell dissolution apparatus was found to be inadequate to accurately study the dissolution profiles of the pulmonary drug delivery systems due to the formation of a gel in the apparatus. Preliminary work on the use of a novel technique to predict the crystallisation of amorphous formulations with terahertz time-domain spectroscopy was also conducted. The system confirmed the re-crystallisation tendencies of several hybrid CS/BSA/PVA formulations. Modification to the experimental setup to probe the formulations at different relative humidities instead of temperatures could yield improved results.","abstract_html":"The therapeutic effect of pulmonary drug delivery systems is limited by its rapid clearance from the lungs by robust clearance mechanisms. By controlling the release of drugs, the therapeutic effect of pulmonary drug delivery systems, as well as patient convenience and compliance could be improved by reducing the number of times drugs need to be administered. In this study, two controlled pulmonary drug delivery systems for drugs of different solubilities were investigated and they were characterised for their viability as effective controlled release pulmonary drug delivery systems, particularly in areas of aerosol performance and dissolution profile. A hybrid protein-polymer controlled release pulmonary drug delivery system was developed to sustain the release of a water-soluble anti-asthma drug, cromolyn sodium (CS). Two excipients with complementary characteristics – a protein, bovine serum albumin, and a polymer, polyvinyl alcohol – were formulated together with CS via co-spray drying, with varying protein-polymer ratios and drug loadings. The hybrid particles showed promise in combining the positive attributes of each excipient, with respirable particles shown to sustain the release of CS with a fine particle fraction of 30%. Combining the two excipients was complex, with further optimisation of the hybrid formulations possible. A commercially available polymer, Soluplus® was spray-dried with a poorly-water soluble corticosteroid, beclomethasone dipropionate (BDP). The resultant respirable powders were shown to have potential for use as a controlled release pulmonary drug delivery system with up to 7-fold improvement in the amount of BDP released compared to spray-dried BDP. The spray-dried BDP-Soluplus® powders were found to be amorphous, and physically stable against re-crystallisation for up to 9 months at accelerated stress test conditions with drug loadings of up to 15 % (w/w). Although it provided a platform to compare between formulations, the USP 4 flow-through cell dissolution apparatus was found to be inadequate to accurately study the dissolution profiles of the pulmonary drug delivery systems due to the formation of a gel in the apparatus. Preliminary work on the use of a novel technique to predict the crystallisation of amorphous formulations with terahertz time-domain spectroscopy was also conducted. The system confirmed the re-crystallisation tendencies of several hybrid CS/BSA/PVA formulations. Modification to the experimental setup to probe the formulations at different relative humidities instead of temperatures could yield improved results.","abstract_has_math":false,"creators":["Chia, Leonard Sze Onn"],"institution":"University of Cambridge","degree_name":"Doctor of Philosophy (PhD)","degree_level":"Doctoral","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Moggridge, Geoffrey Dillwyn","Zeitler, Jochum Axel","Tan, Reginald Beng Hee"],"committee_chairs":[],"committee_members":[],"year":2018,"date_issued":"2018-02-06","date_published":"2018-02-06","updated_at":"2026-07-22T22:24:16Z","subjects":["Pulmonary Delivery","Drug Delivery","Controlled Release"],"languages":["en"],"rights":[],"rights_urls":["https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/c6b8554e-6f51-48d7-925c-d41b120e80f0/download","https://creativecommons.org/licenses/by-nc-nd/4.0/"],"identifier_entries":[{"key":"dc:creator.authoridentifier","label":"Author Identifier","values":["0000000187361471","0000000212209990","0000000249580582","0000000329922036"],"render_values":[{"text":"0000-0001-8736-1471","href":"https://orcid.org/0000-0001-8736-1471","code":true},{"text":"0000-0002-1220-9990","href":"https://orcid.org/0000-0002-1220-9990","code":true},{"text":"0000-0002-4958-0582","href":"https://orcid.org/0000-0002-4958-0582","code":true},{"text":"0000-0003-2992-2036","href":"https://orcid.org/0000-0003-2992-2036","code":true}]}]},"links":{"outbound_url":"https://doi.org/10.17863/CAM.20215","outbound_label":"DOI","outbound_source":"dc:identifier.doi"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Moggridge, Geoffrey Dillwyn","Zeitler, Jochum Axel","Tan, Reginald Beng Hee"]},{"key":"dc:contributor.sponsor","label":"Sponsor","values":["A*STAR Graduate Scholarship (Overseas)"]},{"key":"dc:creator","label":"Author","values":["Chia, Leonard Sze Onn"]},{"key":"dc:creator.authoridentifier","label":"Author Identifier","values":["0000000187361471","0000000212209990","0000000249580582","0000000329922036"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.issued","label":"Date","values":["2018-02-06"]},{"key":"dc:publisher.institution","label":"Dc Publisher Institution","values":["University of Cambridge"]},{"key":"dc:relation.isreferencedby.uri","label":"Dc Relation Isreferencedby URI","values":["https://www.repository.cam.ac.uk/handle/1810/273209"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["Doctoral"]},{"key":"dc:type.qualificationname","label":"Dc Type Qualificationname","values":["Doctor of Philosophy (PhD)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Pulmonary Delivery","Drug Delivery","Controlled Release"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/c6b8554e-6f51-48d7-925c-d41b120e80f0/download","https://creativecommons.org/licenses/by-nc-nd/4.0/"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.doi","label":"DOI","values":["10.17863/CAM.20215"]},{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/a4b9753a-eae8-46af-b541-bf7894a14c3d/download"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["The therapeutic effect of pulmonary drug delivery systems is limited by its rapid clearance from the lungs by robust clearance mechanisms. By controlling the release of drugs, the therapeutic effect of pulmonary drug delivery systems, as well as patient convenience and compliance could be improved by reducing the number of times drugs need to be administered. In this study, two controlled pulmonary drug delivery systems for drugs of different solubilities were investigated and they were characterised for their viability as effective controlled release pulmonary drug delivery systems, particularly in areas of aerosol performance and dissolution profile. A hybrid protein-polymer controlled release pulmonary drug delivery system was developed to sustain the release of a water-soluble anti-asthma drug, cromolyn sodium (CS). Two excipients with complementary characteristics – a protein, bovine serum albumin, and a polymer, polyvinyl alcohol – were formulated together with CS via co-spray drying, with varying protein-polymer ratios and drug loadings. The hybrid particles showed promise in combining the positive attributes of each excipient, with respirable particles shown to sustain the release of CS with a fine particle fraction of 30%. Combining the two excipients was complex, with further optimisation of the hybrid formulations possible. A commercially available polymer, Soluplus® was spray-dried with a poorly-water soluble corticosteroid, beclomethasone dipropionate (BDP). The resultant respirable powders were shown to have potential for use as a controlled release pulmonary drug delivery system with up to 7-fold improvement in the amount of BDP released compared to spray-dried BDP. The spray-dried BDP-Soluplus® powders were found to be amorphous, and physically stable against re-crystallisation for up to 9 months at accelerated stress test conditions with drug loadings of up to 15 % (w/w). Although it provided a platform to compare between formulations, the USP 4 flow-through cell dissolution apparatus was found to be inadequate to accurately study the dissolution profiles of the pulmonary drug delivery systems due to the formation of a gel in the apparatus. Preliminary work on the use of a novel technique to predict the crystallisation of amorphous formulations with terahertz time-domain spectroscopy was also conducted. The system confirmed the re-crystallisation tendencies of several hybrid CS/BSA/PVA formulations. Modification to the experimental setup to probe the formulations at different relative humidities instead of temperatures could yield improved results."]},{"key":"dc:format.checksum.md5","label":"Dc Format Checksum Md5","values":["87eda9de84448d1f82354d60eee3eb5f","cc31f5f11dcb88c2601d2690ca682258"]},{"key":"dc:title","label":"Title","values":["Investigating Controlled Release Pulmonary Drug Delivery Systems"]}]}],"canonical_facts":{"dc:contributor.advisor":["Moggridge, Geoffrey Dillwyn","Zeitler, Jochum Axel","Tan, Reginald Beng Hee"],"dc:contributor.sponsor":["A*STAR Graduate Scholarship (Overseas)"],"dc:creator":["Chia, Leonard Sze Onn"],"dc:creator.authoridentifier":["0000000187361471","0000000212209990","0000000249580582","0000000329922036"],"dc:date.issued":["2018-02-06"],"dc:description.abstract":["The therapeutic effect of pulmonary drug delivery systems is limited by its rapid clearance from the lungs by robust clearance mechanisms. By controlling the release of drugs, the therapeutic effect of pulmonary drug delivery systems, as well as patient convenience and compliance could be improved by reducing the number of times drugs need to be administered. In this study, two controlled pulmonary drug delivery systems for drugs of different solubilities were investigated and they were characterised for their viability as effective controlled release pulmonary drug delivery systems, particularly in areas of aerosol performance and dissolution profile. A hybrid protein-polymer controlled release pulmonary drug delivery system was developed to sustain the release of a water-soluble anti-asthma drug, cromolyn sodium (CS). Two excipients with complementary characteristics – a protein, bovine serum albumin, and a polymer, polyvinyl alcohol – were formulated together with CS via co-spray drying, with varying protein-polymer ratios and drug loadings. The hybrid particles showed promise in combining the positive attributes of each excipient, with respirable particles shown to sustain the release of CS with a fine particle fraction of 30%. Combining the two excipients was complex, with further optimisation of the hybrid formulations possible. A commercially available polymer, Soluplus® was spray-dried with a poorly-water soluble corticosteroid, beclomethasone dipropionate (BDP). The resultant respirable powders were shown to have potential for use as a controlled release pulmonary drug delivery system with up to 7-fold improvement in the amount of BDP released compared to spray-dried BDP. The spray-dried BDP-Soluplus® powders were found to be amorphous, and physically stable against re-crystallisation for up to 9 months at accelerated stress test conditions with drug loadings of up to 15 % (w/w). Although it provided a platform to compare between formulations, the USP 4 flow-through cell dissolution apparatus was found to be inadequate to accurately study the dissolution profiles of the pulmonary drug delivery systems due to the formation of a gel in the apparatus. Preliminary work on the use of a novel technique to predict the crystallisation of amorphous formulations with terahertz time-domain spectroscopy was also conducted. The system confirmed the re-crystallisation tendencies of several hybrid CS/BSA/PVA formulations. Modification to the experimental setup to probe the formulations at different relative humidities instead of temperatures could yield improved results."],"dc:format.checksum.md5":["87eda9de84448d1f82354d60eee3eb5f","cc31f5f11dcb88c2601d2690ca682258"],"dc:identifier.doi":["10.17863/CAM.20215"],"dc:identifier.uri":["https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/a4b9753a-eae8-46af-b541-bf7894a14c3d/download"],"dc:language":["en"],"dc:publisher.institution":["University of Cambridge"],"dc:relation.isreferencedby.uri":["https://www.repository.cam.ac.uk/handle/1810/273209"],"dc:rights":["https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/c6b8554e-6f51-48d7-925c-d41b120e80f0/download","https://creativecommons.org/licenses/by-nc-nd/4.0/"],"dc:subject":["Pulmonary Delivery","Drug Delivery","Controlled Release"],"dc:title":["Investigating Controlled Release Pulmonary Drug Delivery Systems"],"dc:type":["Thesis"],"dc:type.qualificationlevel":["Doctoral"],"dc:type.qualificationname":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-22T22:24:16Z"}