Department of Pharmacy, Laboratory of Analytical Chemistry, University of Liège, Liège, Belgium.
Anal Chim Acta. 2011 Aug 5;699(1):96-106. doi: 10.1016/j.aca.2011.05.006. Epub 2011 May 11.
Using near infrared (NIR) and Raman spectroscopy as PAT tools, 3 critical quality attributes of a silicone-based drug reservoir were studied. First, the Active Pharmaceutical Ingredient (API) homogeneity in the reservoir was evaluated using Raman spectroscopy (mapping): the API distribution within the industrial drug reservoirs was found to be homogeneous while API aggregates were detected in laboratory scale samples manufactured with a non optimal mixing process. Second, the crosslinking process of the reservoirs was monitored at different temperatures with NIR spectroscopy. Conformity tests and Principal Component Analysis (PCA) were performed on the collected data to find out the relation between the temperature and the time necessary to reach the crosslinking endpoints. An agreement was found between the conformity test results and the PCA results. Compared to the conformity test method, PCA had the advantage to discriminate the heating effect from the crosslinking effect occurring together during the monitored process. Therefore the 2 approaches were found to be complementary. Third, based on the HPLC reference method, a NIR model able to quantify the API in the drug reservoir was developed and thoroughly validated. Partial Least Squares (PLS) regression on the calibration set was performed to build prediction models of which the ability to quantify accurately was tested with the external validation set. The 1.2% Root Mean Squared Error of Prediction (RMSEP) of the NIR model indicated the global accuracy of the model. The accuracy profile based on tolerance intervals was used to generate a complete validation report. The 95% tolerance interval calculated on the validation results indicated that each future result will have a relative error below ±5% with a probability of at least 95%. In conclusion, 3 critical quality attributes of silicone-based drug reservoirs were quickly and efficiently evaluated by NIR and Raman spectroscopy.
利用近红外（NIR）和拉曼光谱作为 PAT 工具，研究了一种硅基药物储库的 3 个关键质量属性。首先，使用拉曼光谱（映射）评估储库中的活性药物成分（API）均匀性：发现工业药物储库中的 API 分布均匀，而在使用非最佳混合工艺制造的实验室规模样品中检测到 API 聚集物。其次，使用 NIR 光谱在不同温度下监测储库的交联过程。对收集的数据进行一致性测试和主成分分析（PCA），以找出温度与达到交联终点所需时间之间的关系。一致性测试结果和 PCA 结果之间存在一致性。与一致性测试方法相比，PCA 具有从监测过程中同时发生的交联效应和加热效应中区分的优势。因此，这两种方法被发现是互补的。第三，基于 HPLC 参考方法，开发了一种能够定量药物储库中 API 的 NIR 模型，并对其进行了彻底验证。在校准集上进行偏最小二乘（PLS）回归，以建立预测模型，并用外部验证集测试其准确定量的能力。NIR 模型的 1.2%预测均方根误差（RMSEP）表明了模型的整体准确性。基于公差区间的准确性概况用于生成完整的验证报告。计算验证结果的 95%公差区间表明，每个未来的结果将具有相对误差低于±5%的概率至少为 95%。总之，通过 NIR 和拉曼光谱快速有效地评估了硅基药物储库的 3 个关键质量属性。
