Determining particle size and water content by near-infrared spectroscopy in the granulation of naproxen sodium

• Published in: Journal of pharmaceutical and biomedical analysis 2018-03, Vol.151, p.209-218
• Main Authors: Bär, David, Debus, Heiko, Brzenczek, Sina, Fischer, Wolfgang, Imming, Peter
• Format: Article
• Language: English
• Subjects: Granulation; Naproxen sodium; Near-infrared spectroscopy; Particle size; Pharmaceutical technology; Water content
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2018.01.005

•First NIR method for water content in drug substance granules (Naproxen Sodium) to monitor different stages of hydration.•Simultaneous NIR particle size determination of Naproxen Sodium granules during a wet granulation.•Test-Set Validation and PLS Regression as chemometric tools were used to be suitable for production-scale requirements.•The NIR methods were developed according to FDA and EMA guidelines and successfully applied in the analysis of samples. Near-infrared spectroscopy is frequently used by the pharmaceutical industry to monitor and optimize several production processes. In combination with chemometrics, a mathematical-statistical technique, the following advantages of near-infrared spectroscopy can be applied: It is a fast, non-destructive, non-invasive, and economical analytical method. One of the most advanced and popular chemometric technique is the partial least square algorithm with its best applicability in routine and its results. The required reference analytic enables the analysis of various parameters of interest, for example, moisture content, particle size, and many others. Parameters like the correlation coefficient, root mean square error of prediction, root mean square error of calibration, and root mean square error of validation have been used for evaluating the applicability and robustness of these analytical methods developed. This study deals with investigating a Naproxen Sodium granulation process using near-infrared spectroscopy and the development of water content and particle-size methods. For the water content method, one should consider a maximum water content of about 21% in the granulation process, which must be confirmed by the loss on drying. Further influences to be considered are the constantly changing product temperature, rising to about 54 °C, the creation of hydrated states of Naproxen Sodium when using a maximum of about 21% water content, and the large quantity of about 87% Naproxen Sodium in the formulation. It was considered to use a combination of these influences in developing the near-infrared spectroscopy method for the water content of Naproxen Sodium granules. The “Root Mean Square Error” was 0.25% for calibration dataset and 0.30% for the validation dataset, which was obtained after different stages of optimization by multiplicative scatter correction and the first derivative. Using laser diffraction, the granules have been analyzed for particle sizes and obtaining the summary sieve sizes of >6