Topical Semisolid Drug Product Critical Quality Attributes with Relevance to Cutaneous Bioavailability and Pharmacokinetics: Part I-Bioequivalence of Acyclovir Topical Creams.

Autor: Mohammed YH; Therapeutics Research Centre, Frazer Institute, The University of Queensland, Brisbane, Australia. Y.Mohammed@uq.edu.au.; School of Pharmacy, The University of Queensland, Woolloongabba, QLD, 4102, Australia. Y.Mohammed@uq.edu.au., Namjoshi SN; Therapeutics Research Centre, Frazer Institute, The University of Queensland, Brisbane, Australia., Jung N; Institute of Pharmaceutical Technology, Goethe University, Frankfurt, Germany., Windbergs M; Institute of Pharmaceutical Technology, Goethe University, Frankfurt, Germany., Benson HAE; Curtin Medical School, Curtin University, Perth, WA, Australia., Grice JE; Therapeutics Research Centre, Frazer Institute, The University of Queensland, Brisbane, Australia., Raney SG; Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, United States Food and Drug Administration, Silver Spring, MD, USA., Roberts MS; Therapeutics Research Centre, Frazer Institute, The University of Queensland, Brisbane, Australia.; School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia.; Therapeutics Research Centre, Basil Hetzel Institute for Translational Medical Research, The Queen Elizabeth Hospital, Adelaide, Australia.
Jazyk: angličtina
Zdroj: Pharmaceutical research [Pharm Res] 2024 Jul; Vol. 41 (7), pp. 1507-1520. Date of Electronic Publication: 2024 Jul 02.
DOI: 10.1007/s11095-024-03736-9
Abstrakt: Purpose: To develop a toolkit of test methods for characterizing potentially critical quality attributes (CQAs) of topical semisolid products and to evaluate how CQAs influence the rate and extent of active ingredient bioavailability (BA) by monitoring cutaneous pharmacokinetics (PK) using an In Vitro Permeation Test (IVPT).
Methods: Product attributes representing the physicochemical and structural (Q3) arrangement of matter, such as attributes of particles and globules, were assessed for a set of test acyclovir creams (Aciclostad® and Acyclovir 1A Pharma) and compared to a set of reference acyclovir creams (Zovirax® US, Zovirax® UK and Zovirax® Australia). IVPT studies were performed with all these creams using heat-separated human epidermis, evaluated with both, static Franz-type diffusion cells and a flow through diffusion cell system.
Results: A toolkit developed to characterize quality and performance attributes of these acyclovir topical cream products identified certain differences in the Q3 attributes and the cutaneous PK of acyclovir between the test and reference sets of products. The cutaneous BA of acyclovir from the set of reference creams was substantially higher than from the set of test creams.
Conclusions: This research elucidates how differences in the composition or manufacturing of product formulations can alter Q3 attributes that modulate myriad aspects of topical product performance. The results demonstrate the importance of understanding the Q3 attributes of topical semisolid drug products, and of developing appropriate product characterization tests. The toolkit developed here can be utilized to guide topical product development, and to mitigate the risk of differences in product performance, thereby supporting a demonstration of bioequivalence (BE) for prospective topical generic products and reducing the reliance on comparative clinical endpoint BE studies.
(© 2024. The Author(s).)
Databáze: MEDLINE
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