Investigation of the Impact of Manufacturing Methods on Protein-Based Long-Acting Injectable Formulations: A Comparative Assessment for Microfluidics vs. Conventional Methods.

IF 4.9 3区 医学 Q1 PHARMACOLOGY & PHARMACY Pharmaceutics Pub Date : 2024-09-27 DOI:10.3390/pharmaceutics16101264
Nihan Yonet-Tanyeri, Robert S Parker, Louis D Falo, Steven R Little
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Abstract

Background/Objectives: Microparticle-based drug delivery systems offer several advantages for protein-based drug formulations, enhancing patient compliance and therapeutic efficiency through the sustained delivery of the active pharmaceutical ingredient. Over the past few decades, the microfluidics method has emerged as a continuous manufacturing process for preparing drug-encapsulating microparticles, mainly for small molecule drugs. However, comparative assessments for the conventional batch method vs. the microfluidics method for protein-based drug formulations have been lacking. The main objective of this study was to generate immunomodulatory protein drug-loaded injectable formulations using both conventional batch and microfluidics methods.

Methods: Therefore, rhCCL22-loaded poly(lactic-co-glycolic) acid (PLGA) microparticles were prepared by conventional homogenization and microfluidics methods.

Results: The resulting microparticles were analyzed comparatively, focusing on critical quality attributes such as microparticle size, size distribution, morphology, drug encapsulation efficiency, release kinetics, and batch-to-batch variations in relation to the manufacturing method. Our results demonstrated that the conventional method resulted in microparticles with denser surface porosity and wider size distribution as opposed to microparticles prepared by the microfluidics method, which could contribute to a significant difference in the drug-release kinetics. Additionally, our findings indicated minimal variation within batches for the microparticles prepared by the microfluidics method.

Conclusion: Overall, this study highlights the comparative assessment of several critical quality attributes and batch variations associated with the manufacturing methods of protein-loaded microparticles which is crucial for ensuring consistency in efficacy, regulatory compliance, and quality control in the drug formulation manufacturing process.

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生产方法对蛋白质长效注射剂配方影响的调查:微流控与传统方法的比较评估。
背景/目标:基于微粒的给药系统为基于蛋白质的药物制剂提供了多种优势,通过持续给药活性药物成分,提高了患者的依从性和治疗效率。在过去几十年中,微流控方法已成为制备药物封装微粒(主要用于小分子药物)的一种连续生产工艺。然而,对于基于蛋白质的药物制剂,一直缺乏传统批量法与微流控方法的比较评估。本研究的主要目的是利用传统批次法和微流体法生成免疫调节蛋白质药物负载注射制剂:因此,采用传统的均质化和微流控方法制备了负载rhCCL22的聚乳酸(PLGA)微颗粒:结果:我们对制备的微颗粒进行了比较分析,重点是微颗粒尺寸、尺寸分布、形态、药物包封效率、释放动力学等关键质量属性,以及与制备方法有关的批次间差异。我们的研究结果表明,与微流控方法制备的微粒相比,传统方法制备的微粒表面孔隙率更大,粒度分布更广,这可能会导致药物释放动力学的显著差异。此外,我们的研究结果表明,微流控方法制备的微颗粒在批次内的差异极小:总之,本研究突出强调了与蛋白质负载微颗粒生产方法相关的几个关键质量属性和批次差异的比较评估,这对于确保药物制剂生产过程中的疗效一致性、合规性和质量控制至关重要。
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来源期刊
Pharmaceutics
Pharmaceutics Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
7.90
自引率
11.10%
发文量
2379
审稿时长
16.41 days
期刊介绍: Pharmaceutics (ISSN 1999-4923) is an open access journal which provides an advanced forum for the science and technology of pharmaceutics and biopharmaceutics. It publishes reviews, regular research papers, communications,  and short notes. Covered topics include pharmacokinetics, toxicokinetics, pharmacodynamics, pharmacogenetics and pharmacogenomics, and pharmaceutical formulation. Our aim is to encourage scientists to publish their experimental and theoretical details in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced.
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