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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
Version: Published version
Publication type: Zeitschriftenaufsatz
Document type specification: Scientific article
License: CC BY
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Journal: Pharmaceutics
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

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