Determination of carbamazepine polymorphic contents in double-layered tablets using transmittance- and reflectance-near-infrared spectroscopy involving chemometrics

Abstract

Background: Since polymorphs exhibit differences in chemical and physicochemical stability, characteristics, and dissolution rate of the bulk powder, they may significantly affect on the bioavailability of pharmaceutical compounds. Aim: The purpose of the present study is to establish a method for determining the carbamazepine (CBZ) polymorphic content of a double-layered tablet containing various ratios of forms I and III by using transmittance- and reflectance-near-infrared (TNIR and RNIR) spectroscopy involving chemometrics. Methods: Both TNIR and RNIR instruments were used to analyze both top (form I) and wire (form III) sides of the compacts, respectively. NIR spectra were analyzed to predict polymorphic content by a principal component regression analysis. NIR data of the tablets were divided into two wavelength ranges: between 860 and 1680 nm (FW), and 1245 and 1285 nm (NW). Results: The calibration models for polymorphic content based on TNIR had a linear relationship, but those based on RNIR did not. The accuracy of the calibration models suggested that the double-sided data set is more robust than the single-sided data set. Since the spectra of FW involved various information, the calibration models showed a linear correlation, but it is difficult to understand their model. In contrast, those of NW provided limited information on polymorphic forms making it very easy to understand the model. Conclusion: Limiting the wavelength of the spectra is useful to help understand the calibration-complicated model.

Keywords:

• Carbamazepine polymorph
• chemometrics
• double-layered tablet
• Fourier-transformed near-infrared spectroscopy
• principal component regression analysis

Acknowledgments

The authors thank Mr. Yukihiro Ohsaka, Kobe Pharmaceutical University for his experimental assistance.

Declaration of interest

This work was supported in part by a grant-in-aid for Scientific Research (Scientific Research, C, No. 17500322) and MEXT HAITEKU (2004–2008) from the Ministry of Education, Culture, Sports, Sciences and Technology, Japan. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this paper.