Quantifying crystallinity of amlodipine maleate in amorphous solid dispersions produced by fluidized bed granulation using PAT tools

IF 4.3 3区 医学 Q1 PHARMACOLOGY & PHARMACY European Journal of Pharmaceutical Sciences Pub Date : 2025-01-17 DOI:10.1016/j.ejps.2025.107018
Sandi Svetič , Laura Medved , Franc Vrečer , Klemen Korasa
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Abstract

One of the main concerns with formulations containing amorphous solid dispersions (ASDs) is their physical stability. Stability can be compromised if a formulation contains any residual crystallinity of an active pharmaceutical ingredient (API) that could act as seeds for further crystallisation. This study presents four methods for crystalline amlodipine maleate quantification in ASD, which were developed using one Raman and three NIR process analysers. A preliminary analysis revealed distinct differences between amorphous and non-amorphous forms of the API, both in the API alone and in the formulation. These differences laid the foundation for model development in subsequent steps. The development of four partial least squares (PLS) models proceeded through two stages, initially using a single granulation batch dataset for training, and then expanding to include three batches. Their predictability was evaluated on an additional batch dataset. Models were evaluated primarily using root mean square error of prediction (RMSEP), residual prediction deviation (RPD), and limit of detection along with other metrics. To the best of authors’ knowledge, this is the first study that focuses on process monitoring of fluidized bed granulation used in preparation of ASD. The results of this study and their interpretations present novel aspects of Raman and NIR process analyser applications in combination with PLS.

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利用PAT工具定量定量流化床造粒生产的马来酸氨氯地平非晶态固体分散体的结晶度。
对于含有非晶固体分散体(ASDs)的配方,主要关注的问题之一是它们的物理稳定性。如果配方中含有活性药物成分(API)的残余结晶度,可能会影响稳定性,从而成为进一步结晶的种子。本研究建立了4种ASD中马来酸氨氯地平晶体定量方法,分别采用1台拉曼光谱仪和3台近红外光谱仪。初步分析显示,在原料药的非晶态和非晶态形式之间存在明显差异,无论是在原料药本身还是在配方中。这些差异为后续步骤的模型开发奠定了基础。四个偏最小二乘(PLS)模型的开发经历了两个阶段,最初使用单个颗粒批数据集进行训练,然后扩展到包括三个批次。它们的可预测性是在一个额外的批处理数据集上评估的。评估模型主要使用预测均方根误差(RMSEP)、残差预测偏差(RPD)和检出限以及其他指标。据作者所知,这是第一个专注于ASD制备中流化床造粒过程监测的研究。本研究的结果及其解释提出了拉曼和近红外过程分析仪与PLS结合应用的新方面。
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来源期刊
CiteScore
9.60
自引率
2.20%
发文量
248
审稿时长
50 days
期刊介绍: The journal publishes research articles, review articles and scientific commentaries on all aspects of the pharmaceutical sciences with emphasis on conceptual novelty and scientific quality. The Editors welcome articles in this multidisciplinary field, with a focus on topics relevant for drug discovery and development. More specifically, the Journal publishes reports on medicinal chemistry, pharmacology, drug absorption and metabolism, pharmacokinetics and pharmacodynamics, pharmaceutical and biomedical analysis, drug delivery (including gene delivery), drug targeting, pharmaceutical technology, pharmaceutical biotechnology and clinical drug evaluation. The journal will typically not give priority to manuscripts focusing primarily on organic synthesis, natural products, adaptation of analytical approaches, or discussions pertaining to drug policy making. Scientific commentaries and review articles are generally by invitation only or by consent of the Editors. Proceedings of scientific meetings may be published as special issues or supplements to the Journal.
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