{"id":{"repo_id":"cau-kiel","oai_identifier":"oai:macau.uni-kiel.de:macau_mods_00007942"},"canonical_url":"https://search.dev.ndltd.org/etd/cau-kiel/oai:macau.uni-kiel.de:macau_mods_00007942","repository":{"repo_id":"cau-kiel","name":"Christian-Albrechts Universität Kiel","base_url":"https://macau.uni-kiel.de/servlets/OAIDataProvider"},"display":{"title":"Clarithromycin nanocrystals for high-dose inhalation","abstract":"Pneumonia remains a major global cause of morbidity and mortality, especially where access to care is limited. Standard oral / i.v. antibiotics often require high systemic doses to reach effective lung levels, increasing adverse effects, lowering adherence and fostering resistance. This work developed a high-dose inhalable dry-powder approach to deliver clarithromycin locally. Poorly soluble clarithromycin (BCS II) was converted to nanocrystals by wet media milling. Spray-dried hollow microparticles, so called \"Trojan particles\", in which nanocrystals are incorporated in a matrix shell are designed for deep-lung deposition while retaining good flow and dispersion. Hydroxypropyl methylcellulose (HPMC) served as a dual-function excipient, stabilising nanocrystals during milling and acting as the spray-drying matrix, enabling low excipient load. Adding a citric acid/NaOH buffer (pH 5) markedly improved nanocrystal redispersibility in simulated lung fluid. The optimised formulation achieved a fine particle fraction of 52.7%; further spray-drying optimisation did not improve this. In vitro, intrinsic dissolution rate increased 5.5-fold and saturation solubility ~10-fold versus micronised clarithromycin, indicating preserved nanonisation benefits after particle formation. Overall, nanonisation plus Trojan architecture and targeted matrix design represents a promising platform for high-dose inhalable anti-infectives; further biocompatibility, deposition and efficacy studies are needed, and the concept may extend to other poorly soluble drugs.","abstract_html":"Pneumonia remains a major global cause of morbidity and mortality, especially where access to care is limited. Standard oral / i.v. antibiotics often require high systemic doses to reach effective lung levels, increasing adverse effects, lowering adherence and fostering resistance. This work developed a high-dose inhalable dry-powder approach to deliver clarithromycin locally. Poorly soluble clarithromycin (BCS II) was converted to nanocrystals by wet media milling. Spray-dried hollow microparticles, so called "Trojan particles", in which nanocrystals are incorporated in a matrix shell are designed for deep-lung deposition while retaining good flow and dispersion. Hydroxypropyl methylcellulose (HPMC) served as a dual-function excipient, stabilising nanocrystals during milling and acting as the spray-drying matrix, enabling low excipient load. Adding a citric acid/NaOH buffer (pH 5) markedly improved nanocrystal redispersibility in simulated lung fluid. The optimised formulation achieved a fine particle fraction of 52.7%; further spray-drying optimisation did not improve this. In vitro, intrinsic dissolution rate increased 5.5-fold and saturation solubility ~10-fold versus micronised clarithromycin, indicating preserved nanonisation benefits after particle formation. Overall, nanonisation plus Trojan architecture and targeted matrix design represents a promising platform for high-dose inhalable anti-infectives; further biocompatibility, deposition and efficacy studies are needed, and the concept may extend to other poorly soluble drugs.","abstract_has_math":false,"creators":["Neustock, Anna Kristina Luise"],"institution":"Christian-Albrechts-Universität zu Kiel","degree_name":null,"degree_level":"thesis.doctoral","degree_discipline":null,"degree_department":null,"school":null,"contributors":["Scherließ, Regina","Schwarz, Karin"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2026,"date_issued":"2026-01-26","date_published":"2026-01-26","updated_at":"2026-07-24T01:35:31Z","subjects":["High-dose inhalation","Nanocrystals","Trojan particles","Clarithromycin"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://macau.uni-kiel.de/receive/macau_mods_00007942","outbound_label":"Repository record","outbound_source":"source_url"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Scherließ, Regina","Schwarz, Karin"]},{"key":"dc:creator","label":"Author","values":["Neustock, Anna Kristina Luise"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:publisher","label":"Institution","values":["Universitätsbibliothek Kiel"]},{"key":"dc:type","label":"Dc Type","values":["PhDThesis"]},{"key":"thesis:degree_level","label":"Degree Level","values":["thesis.doctoral"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["Christian-Albrechts-Universität zu Kiel"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["High-dose inhalation","Nanocrystals","Trojan particles","Clarithromycin"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Pneumonia remains a major global cause of morbidity and mortality, especially where access to care is limited. Standard oral / i.v. antibiotics often require high systemic doses to reach effective lung levels, increasing adverse effects, lowering adherence and fostering resistance. This work developed a high-dose inhalable dry-powder approach to deliver clarithromycin locally. Poorly soluble clarithromycin (BCS II) was converted to nanocrystals by wet media milling. Spray-dried hollow microparticles, so called \"Trojan particles\", in which nanocrystals are incorporated in a matrix shell are designed for deep-lung deposition while retaining good flow and dispersion. Hydroxypropyl methylcellulose (HPMC) served as a dual-function excipient, stabilising nanocrystals during milling and acting as the spray-drying matrix, enabling low excipient load. Adding a citric acid/NaOH buffer (pH 5) markedly improved nanocrystal redispersibility in simulated lung fluid. The optimised formulation achieved a fine particle fraction of 52.7%; further spray-drying optimisation did not improve this. In vitro, intrinsic dissolution rate increased 5.5-fold and saturation solubility ~10-fold versus micronised clarithromycin, indicating preserved nanonisation benefits after particle formation. Overall, nanonisation plus Trojan architecture and targeted matrix design represents a promising platform for high-dose inhalable anti-infectives; further biocompatibility, deposition and efficacy studies are needed, and the concept may extend to other poorly soluble drugs."]},{"key":"dc:format.medium","label":"Dc Format Medium","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Clarithromycin nanocrystals for high-dose inhalation"]}]}],"canonical_facts":{"dc:contributor":["Scherließ, Regina","Schwarz, Karin"],"dc:creator":["Neustock, Anna Kristina Luise"],"dc:description.abstract":["Pneumonia remains a major global cause of morbidity and mortality, especially where access to care is limited. Standard oral / i.v. antibiotics often require high systemic doses to reach effective lung levels, increasing adverse effects, lowering adherence and fostering resistance. This work developed a high-dose inhalable dry-powder approach to deliver clarithromycin locally. Poorly soluble clarithromycin (BCS II) was converted to nanocrystals by wet media milling. Spray-dried hollow microparticles, so called \"Trojan particles\", in which nanocrystals are incorporated in a matrix shell are designed for deep-lung deposition while retaining good flow and dispersion. Hydroxypropyl methylcellulose (HPMC) served as a dual-function excipient, stabilising nanocrystals during milling and acting as the spray-drying matrix, enabling low excipient load. Adding a citric acid/NaOH buffer (pH 5) markedly improved nanocrystal redispersibility in simulated lung fluid. The optimised formulation achieved a fine particle fraction of 52.7%; further spray-drying optimisation did not improve this. In vitro, intrinsic dissolution rate increased 5.5-fold and saturation solubility ~10-fold versus micronised clarithromycin, indicating preserved nanonisation benefits after particle formation. Overall, nanonisation plus Trojan architecture and targeted matrix design represents a promising platform for high-dose inhalable anti-infectives; further biocompatibility, deposition and efficacy studies are needed, and the concept may extend to other poorly soluble drugs."],"dc:format.medium":["application/pdf"],"dc:publisher":["Universitätsbibliothek Kiel"],"dc:subject":["High-dose inhalation","Nanocrystals","Trojan particles","Clarithromycin"],"dc:title":["Clarithromycin nanocrystals for high-dose inhalation"],"dc:type":["PhDThesis"],"thesis:degree_level":["thesis.doctoral"],"thesis:institution_name":["Christian-Albrechts-Universität zu Kiel"]},"updated_at":"2026-07-24T01:35:31Z"}