Evaluation of the microcrystallinity of a drug substance, indomethacin, in a pharmaceutical model tablet by chemometric FT-Raman spectroscopy
Evaluation of the microcrystallinity of a drug substance, indomethacin, in a pharmaceutical model tablet by chemometric FT-Raman spectroscopy
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DOI：
10.1007/s11095-005-5281-9
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发表时间：
2005-08-01
影响因子：
3.7
通讯作者：
Otsuka, M
中科院分区：
文献类型：
--
作者：
Okumura, T;Otsuka, M
目的.建立一种基于傅里叶变换拉曼光谱的化学计量学方法，用于精确评价药物模型片剂中吲哚美辛（IMC）的微晶度。以各种比例制备无定形和结晶IMC的均匀混合物的标准样品粉末。基于多元散射校正（MSC）+二阶导数变换的拉曼光谱，采用偏最小二乘法（PLS）建立了IMC结晶度的校正模型。还使用具有不同IMC结晶度的均匀标准样品粉末构建了模型药物产品（IMC/甘露醇= 1：9 wt/wt）中IMC结晶度的校准模型。经验证，该技术可检测到模型产品中IMC中2%的无定形或结晶物质（片剂总质量的0.2%）。使用该技术，不仅阐明了压力诱导的非晶化，而且阐明了模型产品片剂压制后表面和内部IMC微晶度的差异。已建立的技术非常适合于原料药和制剂微量分析的精确定量，特别是在片剂的表面和内部。
Purpose. To establish a chemometric method for the precise evaluation of the microcrystallinity of indomethacin (IMC) in a pharmaceutical model tablet, based on FT-Raman spectroscopy.Methods. Standard sample powders of homogeneous mixtures of amorphous and crystalline IMC were prepared in various proportions. A calibration model for the crystallinity of IMC was constructed by partial least-square (PLS) analysis based on the multiplicative scatter correction (MSC) + second-derivative transformed Raman spectra. A calibration model for the crystallinity of IMC in a model pharmaceutical product (IMC/mannitol = 1:9 wt/wt) was also constructed using homogeneous standard sample powders of various degrees of crystallinity of IMC.Results. This technique was validated to detect to 2% an amorphous or crystalline material in IMC contained in the model product (0.2% of the total mass of the tablet). Using this technique, not only pressure-induced amorphization but also the difference in microcrystallinity of IMC at the surface and interior of a model product tablet was elucidated after compaction of the tablet.Conclusions. The established technique is ideally suited for precise quantification of microanalysis of drug substances and drug products, particularly at the surface and interior of the tablet.