Development of a Rapid Process Monitoring Method for Dry-Coated Tableting Process by Using Near-Infrared Spectroscopy

Abstract

A nondestructive transmittance near-infrared (NIR) method for detecting off-centered cores in dry-coated (DC) tablets was developed as a monitoring system in the DC tableting process. Caffeine anhydrate was used as a core active pharmaceutical ingredient (API), and DC tablets were made by the direct compression method. NIR spectra were obtained from these intact DC tablets using the transmittance method. The reference assay was performed with HPLC. Calibration models were generated by partial least squares (PLS) regression and principal component regression (PCR) utilizing external validations. Hierarchical cluster analysis (HCA) of the results confirmed that NIR spectroscopy correctly detected off-centered cores in DC tablets. We formulated and used the Centering Index (CI) to evaluate the precision of core alignment and generated an NIR calibration model that could correctly predict this index. The principal component (PC) 1 loading vector of the final calibration model indicated that it could specifically detect the misalignment of tablet cores. The model also had good linearity and accuracy. The CIs of unknown sample tablets predicted by the final calibration model and those calculated through the HPLC analysis were closely parallel with each other. These results demonstrate the validity of the final calibration model and the utility of the transmittance NIR spectroscopic method developed in this study as a monitoring system in DC tableting process.

Sample Size Determination and Statistical Hypothesis Testing for Core Centration in Press Coated Tablets

“…The combinations of different compositions between the core and the coat allows for a large variety of design of the release profile [1,2]. It is important that the core is well centered inside of the tablet to make the tablet more light-stable, more water-stable or to preserve the release properties [2][3][4]. The positioning of the core varies slightly from tablet to tablet during the manufacture process [5][6][7][8][9].…”

“…A quality assessment process needs then to be established to guarantee that the centering of the core stays within certain specifications. Current methods used for evaluating core centration are either imprecise, where the core position is measured "by hand" [1,10], or expensive, where costly diagnostic equipment is required [3]. An option to obtain well-centered cores is to use onestep dry-coated tablets [3,11] but the technology is rather new and not implemented everywhere.…”

“…Current methods used for evaluating core centration are either imprecise, where the core position is measured "by hand" [1,10], or expensive, where costly diagnostic equipment is required [3]. An option to obtain well-centered cores is to use onestep dry-coated tablets [3,11] but the technology is rather new and not implemented everywhere. In this paper, we propose a relatively inexpensive and reliable methodology to monitor core centration during the manufacture of dry-coated tablets.…”