Characterization and Quantitation of Aprepitant Drug Substance Polymorphs by Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy

Abstract

In this study, we report the use of attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FT-IR) for the identification and quantitation of two polymorphs of Aprepitant, a substance P antagonist for chemotherapy-induced emesis. Mixtures of the polymorph pair were prepared by weight and ATR-FT-IR spectra of the powdered samples were obtained over the wavelength range of 700-1500 cm(-1). Significant spectral differences between the two polymorphs at 1140 cm(-1) show that ATR-FT-IR can provide definitive identification of the polymorphs. To investigate the feasibility of ATR-FT-IR for quantitation of polymorphic forms of Aprepitant, a calibration plot was constructed with known mixtures of the two polymorphs by plotting the peak ratio of the second derivative of absorbance spectra against the weight percent of form II in the polymorphic mixture. Using this novel approach, 3 wt % of one crystal form could be detected in mixtures of the two polymorphs. The accuracy of ATR-FT-IR in determining polymorph purity of the drug substance was tested by comparing the results with those obtained by X-ray powder diffractometry (XRPD). Indeed, polymorphic purity results obtained by ATR-FT-IR were found to be in good agreement with the predictions made by XRPD and compared favorably with actual values in the known mixtures. The present study clearly demonstrates the potential of ATR-FT-IR as a quick, easy, and inexpensive alternative to XRPD for the determination of polymorphic identity and purity of solid drug substances. The technique is ideally suited for polymorph analysis, because it is precise, accurate, and requires minimal sample preparation.

Solid-state study of mepivacaine hydrochloride

“…Since MH is a readily soluble drug compound, the existence of polymorphism has no relevance to its typical clinical use as water-dissolved active substance. The present study confirms the potential of ATR FT-IR as a quick, easy and cheaper alternative to XRPD [24]; the technique is ideally suited for polymorph analysis, because it is precise, accurate and requires minimal sample preparation.…”

Characterization and Quantification of Amorphous Material in Milled and Spray-Dried Salbutamol Sulfate: A Comparison of Thermal, Spectroscopic, and Water Vapor Sorption Approaches

“…Helmy et al 34 identified ATR-FTIR as a quantification technique by successfully calculating the contents of aprepitant polymorphs within mixtures. In the present case, the data in Figures 5a and 5b demonstrated the ability of ATR-FTIR to differentiate between the amorphous and crystalline salbutamol sulfate; in particular, the peaks in the wavelength range of 1500 to 900 cm −1 had been shown to be especially sensitive to differences in crystallinity.…”

IR spectroscopy together with multivariate data analysis as a process analytical tool for in-line monitoring of crystallization process and solid-state analysis of crystalline product

“…PLS model with proper number of dimensions was derived and the model was validated using external test set. Detailed explanation of calibration routines applied in this context is described in [12].…”

“…Additional technique is beneficial to confirm the estimation derived from XRPD measurements. Vibration spectroscopic techniques such as diffuse reflectance (DRIFT) and attenuated total reflection (ATR) in the mid-FTIR bandwidth as well as NIR have previously been applied in polymorph characterizations [12][13][14][15][16].…”