Takehiro Okumura1, Makoto Otsuka. 1. Organic Synthesis Research Laboratory, Sumitomo Chemical Co., Ltd., Kasugade-naka, Konohana-ku, Osaka, 554-8558, Japan. okumurat2@sc.sumitomo-chem.co.jp
Abstract
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.
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.
Authors: Christopher M Hartshorn; Young Jong Lee; Charles H Camp; Zhen Liu; John Heddleston; Nicole Canfield; Timothy A Rhodes; Angela R Hight Walker; Patrick J Marsac; Marcus T Cicerone Journal: Anal Chem Date: 2013-08-20 Impact factor: 6.986