In vitro and in vivo characterization of Invega Sustenna® (paliperidone palmitate long-acting injectable suspension).

Autor: Li J; Department of Pharmaceutical Sciences and the Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA., Rodriguez A; Department of Pharmaceutical Sciences and the Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA., Wang K; Department of Pharmaceutical Sciences and the Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA., Olsen K; Department of Pharmaceutical Sciences and the Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA., Wang Y; Division of Therapeutic Performance 1, Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration. Silver Spring, MD 20993, USA., Schwendeman A; Department of Pharmaceutical Sciences and the Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: annaschw@umich.edu.
Jazyk: angličtina
Zdroj: European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V [Eur J Pharm Biopharm] 2024 Dec 06, pp. 114613. Date of Electronic Publication: 2024 Dec 06.
DOI: 10.1016/j.ejpb.2024.114613
Abstrakt: The aim of this study was to comprehensively characterize paliperidone palmitate (PP) long-acting suspension (Invega Sustenna®) through reverse engineering. We developed a series of analytical methods to assess critical quality attributes of four batches of Invega Sustenna®. The size distributions of the four batches of suspensions were measured using laser diffraction, and variations in the D50 and D90 parameters were observed. The morphology of suspension was determined through scanning electron microscope (SEM), which exhibited irregular granular shape across all batches. The size distributions determined by SEM images were similar to the laser diffraction results. Thermal characteristics were detected using differential scanning calorimetry (DSC) and crystalline properties were assessed by powder X-ray diffraction (PXRD), displaying consistency among the four batches in these two aspects. In vitro dissolution methods (sample separation and dialysis bag methods) were developed to evaluate the release behaviors of Invega Sustenna® and four lots showed a similar dissolution pattern. Furthermore, following a single-dose intramuscular administration to rats, two batches of Invega Sustenna® with the largest size differences demonstrated comparable plasma concentration-time profiles and pharmacokinetics parameters, indicative of one month long-acting release. In summary, we established a systematic quality characteristics assessment for Invega Sustenna®, including particle size distribution, particle morphology, thermal characteristics, crystalline properties, in vitro dissolution kinetics and in vivo pharmacokinetics. Our work will assist pharmaceutical companies and regulatory agencies in the development and regulatory assessment of novel or generic products of long-acting injectable suspension.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024. Published by Elsevier B.V.)
Databáze: MEDLINE
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