QbD Approach-Based Preparation and Optimization of Hydrophobic Ion-Pairing Complex of Lysozyme with Sodium Dodecyl Sulphate to Enhance Stability in Lipid-Based Carriers.

Autor: Hassan AAA; Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, Eötvös u. 6., H-6720 Szeged, Hungary.; Department of Pharmaceutics, Faculty of Pharmacy, University of Khartoum, Khartoum P.O. Box 1996, Sudan., Sovány T; Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, Eötvös u. 6., H-6720 Szeged, Hungary., Pamlényi K; Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, Eötvös u. 6., H-6720 Szeged, Hungary., Deák M; Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, Eötvös u. 6., H-6720 Szeged, Hungary., Hornok V; Interdisciplinary Excellence Center, Department of Physical Chemistry and Materials Science, University of Szeged, Rerrich B. Sqr. 1, H-6720 Szeged, Hungary., Csapó E; Interdisciplinary Excellence Center, Department of Physical Chemistry and Materials Science, University of Szeged, Rerrich B. Sqr. 1, H-6720 Szeged, Hungary.; MTA-SZTE Lendület 'Momentum' Noble Metal Nanostructures Research Group, University of Szeged, Rerrich B. Sqr. 1, H-6720 Szeged, Hungary., Regdon G Jr; Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, Eötvös u. 6., H-6720 Szeged, Hungary., Csóka I; Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, Eötvös u. 6., H-6720 Szeged, Hungary., Kristó K; Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, Eötvös u. 6., H-6720 Szeged, Hungary.
Jazyk: angličtina
Zdroj: Pharmaceutics [Pharmaceutics] 2024 Apr 26; Vol. 16 (5). Date of Electronic Publication: 2024 Apr 26.
DOI: 10.3390/pharmaceutics16050589
Abstrakt: Hydrophobic ion pairing (HIP) complexation was found to be an efficient approach in modulating the release and enhancing the stability and encapsulation of hydrophilic macromolecules such as proteins in hydrophobic nano/microcarriers. The present work strives to develop and optimize the preparation of the HIP complex of the antimicrobial enzyme lysozyme (LYZ) with the ion-pairing agent (IPA) sodium dodecyl sulphate (SDS) relying on the quality-by-design (QbD) approach. The quality target product profile (QTPP) includes the achievement of maximal lipophilicity in a reversible manner to enable the maintenance of biological activity. The related critical quality attributes (CQAs) were defined as complexation efficacy, complex stability, enzyme recovery and activity. Three risk assessment (RA) tools were used to identify and rank the critical process parameters (CPPs) and critical material attributes (CMAs). From this assessment, the pH of the medium, LYZ:SDS molar ratio and drying conditions were determined as high-risk factors that need to be investigated. To the best of our knowledge, for the first time, electrostatic titration was used as a smart approach to determine the optimum molar ratio at different pH values. Based on the predefined CQAs, pH 8 with an LYZ/SDS molar ratio of 1:8 was found to be the optimal condition for complexation efficiency and recovery (%) of a biologically active enzyme. A cost-effective drying process based on a ventilated oven was developed, which resulted in complex qualities comparable to those obtained by the commonly used freeze-drying method. In a nutshell, the optimum conditions for the preparation of the LYZ/SDS HIP complex were efficiently facilitated by the rational application of QbD principles and the utilization of efficient electrostatic titration and ventilated oven-drying methods.
Competing Interests: The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.
Databáze: MEDLINE
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