Quantitative analysis of polymorphs in binary and multi-component powder mixtures by near-infrared reflectance spectroscopy

Near-infrared reflectance spectroscopy was employed to quantify polymorphs in binary and multi-component powder mixtures. Sulfamethoxazole (SMZ) forms I and II were used as model polymorphs for this study. The instrument repr oducibility, method error, precision, and limits of detection and quantific ation of the method were assessed. Physical mixtures of the polymorph pair were made by weight, ranging from 0 to 100% SMZ form I in II. Near-infrared spectra of the powder samples contained in glass vials were obtained over the wavelength region of 1100-2500 nm. A calibration plot was constructed b y plotting SMZ form I weight percent against a ratio of second derivative v alues of log(l/R') (where R' is the relative reflectance) versus wavelength . The coefficients of determination, R-2, were generally greater than 0.999 7 and standard errors were low for all the systems. Instrument error was as sessed by analyzing a sample 10 times without perturbation. Method error wa s assessed in the same manner except the sample was re-mixed between analys es. A precision study was conducted by analyzing aliquots from a larger hom ogeneous sample. Limits of detection (LOD) and quantification (LOQ) were de termined from the standard deviation of the response of the blank samples ( 100% SMZ form II, undiluted or diluted with 60% lactose). These limits were subsequently validated with independent samples. The results show that pol ymorphs can be quantified in binary and multi-component mixtures in the 2% polymorph composition range. These studies indicate that NIPS is a precise and accurate quantitative tool for determination of polymorphs in the solid -state, is comparable to other characterization techniques, and is more con venient to use than many other methods. (C) 2000 Elsevier Science B.V. All rights reserved.