Determination of polymorphic purity by near infrared spectrometry

Abstract

Differences in physical and chemical properties between polymorphic compounds (e.g. solubility, dissolution rate, chemical reactivity, resistance to degradation, bioavailability) are highly significant for the pharmaceutical industry, which requires effective methods to control the polymorph of interest in the active principle and also to detect and determine the undesirable form. This paper reports on the characterization and determination of a crystalline and an amorphous polymorphic compound of the antibiotic miokamycin by near infrared spectrometry (NIRS). Based on spectral differences between the two, a new analytical method for determining the crystalline form was developed. The underlying study was approached in both qualitative (classification by binary logistic regression) and quantitative terms (quantitation of the crystalline miokamycin content by multivariate calibration). Logistic regression allows one to accurately classify all samples of amorphous miokamycin and also those contaminated with more than 0.3% of the crystalline form. Low contents (<10%) of the crystalline form were determined by testing various PLS1 calibration models involving different spectral modes and ranges, with relative standard errors (RSEs) in the region of 3.5%. The limit of detection (LOD) thus achieved is 0.37% and coincides with the limit of contamination established by logistic regression. The simplicity, expeditiousness and reliability of the proposed method make it an effective tool for controlling polymorphic purity.