Ito Masatomo, Suzuki Tatsuya, Yada Shuichi, Kusai Akira, Nakagami Hiroaki, Yonemochi Etsuo, Terada Katsuhide
Formulation Technology Research Laboratories, Daiichi-Sankyo Co. Ltd., 1-12-1 Shinomiya, Hiratsuka, Kanagawa 254-0014, Japan.
J Pharm Biomed Anal. 2008 Aug 5;47(4-5):819-27. doi: 10.1016/j.jpba.2008.03.033. Epub 2008 Apr 10.
Using near-infrared (NIR) spectroscopy, an assay method which is not affected by such elements of tablet design as thickness, shape, embossing and scored line was developed. Tablets containing caffeine anhydrate were prepared by direct compression at various compression force levels using different shaped punches. NIR spectra were obtained from these intact tablets using the reflectance and transmittance techniques. A reference assay was performed by high-performance liquid chromatography (HPLC). Calibration models were generated by the partial least-squares (PLS) regression. Changes in the tablet thickness, shape, embossing and scored line caused NIR spectral changes in different ways, depending on the technique used. As a result, noticeable errors in drug content prediction occurred using calibration models generated according to the conventional method. On the other hand, when the various tablet design elements which caused the NIR spectral changes were included in the model, the prediction of the drug content in the tablets was scarcely affected by those elements when using either of the techniques. A comparison of these techniques resulted in higher predictability under the tablet design variations using the transmittance technique with preferable linearity and accuracy. This is probably attributed to the transmittance spectra which sensitively reflect the differences in tablet thickness or shape as a result of obtaining information inside the tablets.
利用近红外（NIR）光谱法，开发了一种不受片剂设计的厚度、形状、压纹和刻痕线等因素影响的测定方法。使用不同形状的冲头在不同的压力水平下通过直接压片制备含无水咖啡因的片剂。使用反射率和透射率技术从这些完整片剂中获取近红外光谱。通过高效液相色谱法（HPLC）进行参比测定。通过偏最小二乘法（PLS）回归生成校准模型。片剂的厚度、形状、压纹和刻痕线的变化以不同方式引起近红外光谱变化，这取决于所使用的技术。结果，使用根据传统方法生成的校准模型时，药物含量预测出现明显误差。另一方面，当将引起近红外光谱变化的各种片剂设计因素纳入模型时，使用这两种技术中的任何一种时，片剂中药物含量的预测几乎不受这些因素的影响。对这些技术进行比较后发现，在片剂设计变化的情况下，使用透射率技术具有更高的可预测性，线性度和准确度更佳。这可能归因于透射率光谱，由于获取了片剂内部的信息，它能灵敏地反映片剂厚度或形状的差异。
