Hudovornik Grega, Korasa Klemen, Vrečer Franc
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8000 Novo mesto, Slovenia.
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8000 Novo mesto, Slovenia; University of Ljubljana, Faculty of Pharmacy, Aškerčeva 7, 1000 Ljubljana, Slovenia.
Eur J Pharm Sci. 2015 Jul 30;75:160-8. doi: 10.1016/j.ejps.2015.04.007. Epub 2015 Apr 28.
Special populations including paediatric and elderly patients often need advanced approaches in treatment, such as one-a-day dosing, which is achieved with modified release formulations or alternative routes of applications such as nasogastric route. Pellets are a dosage form that is frequently used in such formulations. The aim of the present work was to study the applicability of two in-line techniques, namely, Near Infrared Spectroscopy (NIR) and Spatial Filtering Technique (SFT) in the pellet coating process. The first objective of our work was to develop a prediction model for moisture content determination with the in-line NIR and to test its robustness in terms of sensitivity to changes in composition of the pellets and performance in wide range of moisture content. Secondly, the in-line SFT measurement was correlated with different off-line particle size methods. The third objective was to evaluate the ability of both in-line techniques for the detection of undesired deviations during the process, such as pellet attrition and agglomeration. Finally, the ability to predict coating thickness with the in-line NIR probe was evaluated. Results suggested that NIR prediction model for moisture content was less robust outside the calibration range and was also sensitive to changes in composition of the film coating. Nevertheless, satisfactory prediction was achieved in the case when coating composition was partially altered and adequate calibration range was used. The SFT probe results were in good correlation with off-line particle size measurement methods and proved to be an effective tool for coating thickness determination during the coating, however, the probe failed to accurately show the actual amount of the agglomerates formed during the process. In experiment when pellet attrition was initiated, both probes successfully detected abrasion of the pellet surface in real time. Furthermore, a predictive NIR model for coating thickness was made and showed a good potential to measure coating thickness in-line, suggesting that the NIR probe can be used as a single tool to monitor water content, coating thickness, and deviations in the coating process.
包括儿科和老年患者在内的特殊人群通常需要先进的治疗方法，例如每日一次给药，这可通过缓释制剂或鼻胃管等替代给药途径来实现。微丸是此类制剂中常用的剂型。本研究的目的是研究两种在线技术，即近红外光谱法（NIR）和空间过滤技术（SFT）在微丸包衣过程中的适用性。我们工作的首要目标是开发一种用于在线近红外光谱法测定水分含量的预测模型，并测试其对微丸组成变化的敏感性以及在广泛水分含量范围内的性能稳健性。其次，将在线SFT测量结果与不同的离线粒度分析方法进行关联。第三个目标是评估这两种在线技术检测过程中不期望偏差（如微丸磨损和团聚）的能力。最后，评估了使用在线近红外探头预测包衣厚度的能力。结果表明，水分含量的近红外预测模型在校准范围之外的稳健性较差，并且对薄膜包衣组成的变化也很敏感。然而，当包衣组成部分改变且使用了足够的校准范围时，仍能获得令人满意的预测结果。SFT探头的结果与离线粒度测量方法具有良好的相关性，并且被证明是包衣过程中测定包衣厚度的有效工具，然而，该探头未能准确显示过程中形成的团聚物的实际数量。在微丸磨损开始的实验中，两种探头均成功实时检测到微丸表面的磨损。此外，建立了包衣厚度的近红外预测模型，该模型显示出在线测量包衣厚度的良好潜力，这表明近红外探头可作为一种单一工具来监测水分含量、包衣厚度以及包衣过程中的偏差。
