Manufacturing Technology Department, Towa Pharmaceutical CO., LTD, Ichiban-cho, Kadoma, Osaka 571-0033, Japan.
Duquesne Center for Pharmaceutical Technology, Duquesne University, Pittsburgh, PA 15282, United States; Duquesne University Graduate School for Pharmaceutical Sciences, Pittsburgh, PA 15282, United States.
Eur J Pharm Biopharm. 2019 Dec;145:35-41. doi: 10.1016/j.ejpb.2019.09.024. Epub 2019 Sep 27.
Film coating of nifedipine tablets is commonly performed to reduce photo-degradation. The coating thickness of these tablets is a primary dictating factor of photo-stability. Terahertz spectroscopy enables accurate measurement of coating thickness. This study identifies a method to determine an end-point of a photo-protective coating process by using coating thickness measurements from terahertz time of flight spectroscopy (THz-TOF). For this method, nifedipine tablets, at different coating thicknesses, were placed in a photostability chamber. The illumination conditions of the coated tablets were adjusted based on the time duration of these tablets inside the chamber. A multiple linear regression model was developed with the coating thickness estimates from THz-TOF and illumination conditions information to predict the amount of drug remaining after photo-degradation (percent label claim). The prediction error of this model was 1.03% label claim in the range of 88.4-100.6% label claim. According to this model, acceptable levels of photo-protection in illumination conditions of up to approximately 700,000 lx hours was achieved at the end of the coating process (approximately 50 µm coating thickness) performed in this study. These results suggest THz-TOF as a viable process analytical technology tool for process understanding and end-point determination of a photo-protective coating process.
硝苯地平片剂的薄膜包衣通常用于减少光降解。这些片剂的涂层厚度是光稳定性的主要决定因素。太赫兹光谱技术能够实现涂层厚度的精确测量。本研究通过使用太赫兹时域光谱(THz-TOF)的涂层厚度测量值,确定了一种通过光保护涂层过程的终点的方法。对于该方法,将具有不同涂层厚度的硝苯地平片剂放置在光稳定性室内。根据片剂在室内的时间长度来调整涂层片剂的照明条件。建立了一个具有涂层厚度估计值和太赫兹时域光谱信息的多元线性回归模型,以预测光降解后剩余的药物量(标签声称的百分比)。该模型的预测误差在 88.4%至 100.6%标签声称范围内为 1.03%标签声称。根据该模型,在本研究中进行的涂层过程结束时(约 50 µm 涂层厚度),可以在高达约 700,000 lx 小时的照明条件下实现可接受的光保护水平。这些结果表明,太赫兹时域光谱技术作为一种可行的过程分析技术工具,可用于了解过程并确定光保护涂层过程的终点。