University of Liege (ULiege), CIRM, Vibra-Santé HUB, Laboratory of Pharmaceutical Analytical Chemistry, CHU, B36, B-4000, Liege, Belgium; Bio-Pharmaceutical and Toxicological Analysis Research Team, Laboratory of Pharmacology and Toxicology, Faculty of Medicine and Pharmacy, University Mohammed V, Rabat, Morocco.
University of Liege (ULiege), CIRM, Vibra-Santé HUB, Laboratory of Pharmaceutical Analytical Chemistry, CHU, B36, B-4000, Liege, Belgium.
J Pharm Biomed Anal. 2021 Mar 20;196:113922. doi: 10.1016/j.jpba.2021.113922. Epub 2021 Jan 26.
The main goal of this work was to test the ability of vibrational spectroscopy techniques to differentiate between different polymorphic forms of fluconazole in pharmaceutical products. These are mostly manufactured with fluconazole as polymorphic form II and form III. These crystalline forms may undergo polymorphic transition during the manufacturing process or storage conditions. Therefore, it is important to have a method to monitor these changes to ensure the stability and efficacy of the drug. Each of FT-IR or FT-NIR spectra were associated to partial least squares-discriminant analysis (PLS-DA) for building classification models to distinguish between form II, form III and monohydrate form. The results has shown that combining either FT-IR or FT-NIR to PLS-DA has a high efficiency to classify various fluconazole polymorphs, with a high sensitivity and specificity. Finally, the selectivity of the PLS-DA models was tested by analyzing separately each of three following samples by FT-IR and FT-NIR: lactose monohydrate, which is an excipient mostly used for manufacturing fluconazole pharmaceutical products, itraconazole and miconazole. These two last compounds mimic potential contaminants and belong to the same class as fluconazole. Based on the plots of Hotelling's T² vs Q residuals, pure compounds of miconazole and itraconazole, that were analyzed separately, were significantly considered outliers and rejected. Furthermore, binary mixtures consist of fluconazole form-II and monohydrate form with different ratios were used to test the suitability of each technique FT-IR and FT-NIR with PLS-DA to detect minimum contaminant or polymorphic conversion from a polymorphic form to another using also the plots of Hotelling's T² vs Q residuals.
这项工作的主要目标是测试振动光谱技术区分药物产品中不同氟康唑多晶型形式的能力。这些药物主要是用多晶型形式 II 和形式 III 的氟康唑制造的。这些晶型形式在制造过程或储存条件下可能会发生多晶型转变。因此，拥有一种监测这些变化的方法对于确保药物的稳定性和疗效非常重要。傅里叶变换红外（FT-IR）或傅里叶变换近红外（FT-NIR）光谱分别与偏最小二乘判别分析（PLS-DA）相关联，以构建分类模型来区分形式 II、形式 III 和一水合物形式。结果表明，将 FT-IR 或 FT-NIR 与 PLS-DA 结合使用，可以高效地对各种氟康唑多晶型进行分类，具有高灵敏度和特异性。最后，通过 FT-IR 和 FT-NIR 分别分析三种以下样品来测试 PLS-DA 模型的选择性：一水乳糖，一水乳糖是制造氟康唑药物产品时常用的赋形剂；伊曲康唑和咪康唑。后两种化合物模拟潜在的污染物，属于与氟康唑同类的化合物。基于 Hotelling 的 T²与 Q 残差的图，单独分析的咪康唑和伊曲康唑的纯化合物被认为是显著的异常值并被拒绝。此外，使用不同比例的氟康唑形式 II 和一水合物形式的二元混合物来测试每种技术 FT-IR 和 FT-NIR 与 PLS-DA 的适用性，以使用 Hotelling 的 T²与 Q 残差的图来检测最小污染物或从一种晶型向另一种晶型的多晶型转变。
