Chemometric evaluation of pharmaceutical properties of antipyrine granules by near-infrared spectroscopy

Abstract

KEYWORDS: agitating granulation, physical properties, near-infrared spectroscopy, chemometrics, principle component regression analysisThe purpose of this research was to apply near-infrared (NIR) spectroscopy with chemometrics to predict the change of pharmaceutical properties of antipyrine granules during granulation by regulation of the amount of water added. The various kinds of granules (mean particle size, 70-750 µm) were obtained from the powder mixture (1 g of antipyrine, 6 g of hydroxypropylcellulose, 140 g of lactose, and 60 g of potato starch) by regulation of the added water amount (11-19 wt/wt%) in a high-speed mixer. The granules were characterized by mean particle size, angle of repose, compressibility, tablet porosity, and tablet hardness as parameters of pharmaceutical properties. To predict the pharmaceutical properties, NIR spectra of the granules were measured and analyzed by principal component regression (PCR) analysis. The mean particle size of the granules increased from 81 µm to 650 µm with an increase in the amount of water, and it was possible to make larger spherical granules with narrow particle size distribution using a high-speed mixer. Angle of repose, compressibility, and porosity of the tablets decreased with an increase of added water, but tablet hardness increased. The independent calibration models to evaluate particle size, angle of repose, and tablet porosity and hardness were established by using PCR based on NIR spectra of granules, respectively. The correlation coefficient constants of calibration curves for prediction of mean particle size, angle of repose, tablet porosity, and tablet hardness were 0.9109, 0.8912, 0.7437, and 0.8064, respectively. It is possible that the pharmaceutical properties of the granule, such as mean particle size, angle of repose, tablet porosity, and tablet hardness, could be predicted by an NIR-chemometric method.

Theoretical Analysis of Tablet Hardness Prediction Using Chemoinformetric Near-Infrared Spectroscopy

“…It is well recognized that a spectral background shift is related to the particle size of samples in the diffuse reflectance method. [13][14][15][16][17][18] Since Otsuka et al 17,18 reported that a background shift was related to a large particle size, more than 50 μm in diameter, the loading vector of PC1 might be related to the particle size or the radius of pores in the tablets. On the other hand, Norris and Williams 16 reported that the slope of the spectral background was proportional to increasing particle size of a fine powder.…”

“…[13][14][15][16][17][18] The measurement of tablet hardness and predictions are therefore necessary for quality control in the pharmaceutical industry, since sufficient mechanical strength of the preparations is important during both the manufacturing process and transport. There are several reports on measurements of tablet mechanical strength using the NIR method.…”

Determination of flow properties of pharmaceutical powders by near infrared spectroscopy

“…Some work has been done in relating the near infrared (NIR) spectrum with tablet hardness, drug stability, tablet coating and particle size of powders [15][16][17][18]. Otsuka et al [19] used NIRS to predict the angle of repose of granules obtained after the granulation process using various amounts of added water using principal component regression (PCR). In the cited work, the authors discuss that the angle of repose is an index to powder flowability and that can be easily predicted by NIRS.…”

Prediction of quality attributes of continuously produced granules using complementary pat tools

“…Only a limited amount of tests was performed, which was covering a small range of residual moisture content (0.43-1.06 % w/w). NIR spectroscopy in combination with multivariate data analysis has also been investigated in order to predict the flowability of both powders [20] and granules [21].…”