1. Startpage
  2. Johannes Gutenberg-Universität Mainz
  3. DFG-491381577-G
Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-8804
Full metadata record
DC FieldValueLanguage
dc.contributor.authorPielenhofer, Jonas-
dc.contributor.authorMeiser, Sophie Luise-
dc.contributor.authorGogoll, Karsten-
dc.contributor.authorCiciliani, Anna-Maria-
dc.contributor.authorDenny, Mark-
dc.contributor.authorKlak, Michael-
dc.contributor.authorLang, Berenice M.-
dc.contributor.authorStaubach, Petra-
dc.contributor.authorGrabbe, Stephan-
dc.contributor.authorSchild, Hansjörg-
dc.contributor.authorRadsak, Markus P.-
dc.contributor.authorSpahn-Langguth, Hilde-
dc.contributor.authorLangguth, Peter-
dc.date.accessioned2023-06-06T07:54:48Z-
dc.date.available2023-06-06T07:54:48Z-
dc.date.issued2023-
dc.identifier.urihttps://openscience.ub.uni-mainz.de/handle/20.500.12030/8820-
dc.description.abstractThe present article exemplifies the application of the concept of quality by design (QbD) for the systematic development of a nanoparticulate imiquimod (IMQ) emulsion gel formulation as an investigational medicinal product (IMP) for evaluation in an academic phase-I/II clinical trial for the treatment of actinic keratosis (AK) against the comparator Aldara (EudraCT: 2015-002203-28). The design of the QbD elements of a quality target product profile (QTPP) enables the identification of the critical quality attributes (CQAs) of the drug product as the content of IMQ, the particle-size distribution, the pH, the rheological properties, the permeation rate and the chemical, physical and microbiological stability. Critical material attributes (CMAs) and critical process parameters (CPPs) are identified by using a risk-based approach in an Ishikawa diagram and in a risk-estimation matrix. In this study, the identified CPPs of the wet media ball-milling process’s milling time and milling speed are evaluated in a central composite design of experiments (DoEs) approach, revealing criticality for both factors for the resulting mean particle size, while only the milling time is significantly affecting the polydispersity. To achieve a mean particle size in the range of 300–400 nm with a minimal PdI, the optimal process conditions are found to be 650 rpm for 135 min. Validating the model reveals a good correlation between the predicted and observed values. Adequate control strategies were implemented for intermediate products as in-process controls (IPCs) and quality control (QC) tests of the identified CQAs. The IPC and QC data from 13 “IMI-Gel” batches manufactured in adherence to good manufacturing practice (GMP) reveal consistent quality with minimal batch-to-batch variability.en_GB
dc.language.isoengde
dc.rightsCC BY*
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/*
dc.subject.ddc540 Chemiede_DE
dc.subject.ddc540 Chemistry and allied sciencesen_GB
dc.titleQuality by design (QbD) approach for a nanoparticulate imiquimod formulation as an investigational medicinal producten_GB
dc.typeZeitschriftenaufsatzde
dc.identifier.doihttp://doi.org/10.25358/openscience-8804-
jgu.type.contenttypeScientific articlede
jgu.type.dinitypearticleen_GB
jgu.type.versionPublished versionde
jgu.type.resourceTextde
jgu.organisation.departmentFB 09 Chemie, Pharmazie u. Geowissensch.de
jgu.organisation.number7950-
jgu.organisation.nameJohannes Gutenberg-Universität Mainz-
jgu.rights.accessrightsopenAccess-
jgu.journal.titlePharmaceuticsde
jgu.journal.volume15de
jgu.pages.alternative514de
jgu.publisher.year2023-
jgu.publisher.nameMDPIde
jgu.publisher.placeLausannede
jgu.publisher.issn1999-4923de
jgu.organisation.placeMainz-
jgu.subject.ddccode540de
jgu.publisher.doi10.3390/pharmaceutics15020514de
jgu.organisation.rorhttps://ror.org/023b0x485-
jgu.subject.dfgNaturwissenschaftende
Appears in collections:DFG-491381577-G

Files in This Item:
  File Description SizeFormat
Thumbnail
quality_by_design_qbd_approac-20230216090914073.pdf4.26 MBAdobe PDFView/Open
Show simple item record