Please use this identifier to cite or link to this item:
http://doi.org/10.25358/openscience-8804
Authors: | Pielenhofer, Jonas Meiser, Sophie Luise Gogoll, Karsten Ciciliani, Anna-Maria Denny, Mark Klak, Michael Lang, Berenice M. Staubach, Petra Grabbe, Stephan Schild, Hansjörg Radsak, Markus P. Spahn-Langguth, Hilde Langguth, Peter |
Title: | Quality by design (QbD) approach for a nanoparticulate imiquimod formulation as an investigational medicinal product |
Online publication date: | 6-Jun-2023 |
Year of first publication: | 2023 |
Language: | english |
Abstract: | The 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. |
DDC: | 540 Chemie 540 Chemistry and allied sciences |
Institution: | Johannes Gutenberg-Universität Mainz |
Department: | FB 09 Chemie, Pharmazie u. Geowissensch. |
Place: | Mainz |
ROR: | https://ror.org/023b0x485 |
DOI: | http://doi.org/10.25358/openscience-8804 |
Version: | Published version |
Publication type: | Zeitschriftenaufsatz |
Document type specification: | Scientific article |
License: | CC BY |
Information on rights of use: | https://creativecommons.org/licenses/by/4.0/ |
Journal: | Pharmaceutics 15 |
Pages or article number: | 514 |
Publisher: | MDPI |
Publisher place: | Lausanne |
Issue date: | 2023 |
ISSN: | 1999-4923 |
Publisher DOI: | 10.3390/pharmaceutics15020514 |
Appears in collections: | DFG-491381577-G |
Files in This Item:
File | Description | Size | Format | ||
---|---|---|---|---|---|
![]() | quality_by_design_qbd_approac-20230216090914073.pdf | 4.26 MB | Adobe PDF | View/Open |