Using multiple Process Analytical Technology probes to monitor multivitamin blends in a tableting feed frame.

As Process Analytical Technology (PAT) implementation grows in the pharmaceutical industry, more studies are being performed to evaluate its suitability in new applications and processes within the manufacturing chain. As the last step in tablet production, the compression stage represents a critical phase that ensures product quality. In-line control put in place at this stage has the potential to detect powder blends that are out of specification limits and, thus, help to improve product quality. The objectives of the present project are to quantify the composition of a commercial 31-component multivitamin powder blend in real time on an industrial feed frame, using 3 different PAT tools: light-induced fluorescence spectroscopy, near infrared spectroscopy and red, green and blue color imaging. To do so, the concentrations of 5 components (Beta-Carotene, Riboflavin, Ferrous Fumarate, Ginseng and Ascorbic Acid) were alternately changed and monitored with one or many probes. Transition periods between batches served to quantify different powder flow dynamics with sequential composition step changes. The results showed that 4 out of 5 components, each present in commercially-relevant concentrations, could be monitored by one or more tools. Flow dynamics were measured and found to vary significantly in different powder blends.

[1]  Wynne W. Chin,et al.  Handbook of Partial Least Squares , 2010 .

[2]  M. Blanco,et al.  Content uniformity and tablet hardness testing of intact pharmaceutical tablets by near infrared spectroscopy: A contribution to process analytical technologies , 2006 .

[3]  Daniel O. Blackwood,et al.  Monitoring blend potency in a tablet press feed frame using near infrared spectroscopy. , 2013, Journal of pharmaceutical and biomedical analysis.

[4]  Chee‐Kong Lai,et al.  Application of a fluorescence sensor for miniscale on-line monitoring of powder mixing kinetics. , 2004, Journal of pharmaceutical sciences.

[5]  R. Gosselin,et al.  Development of a multivariate light-induced fluorescence (LIF) PAT tool for in-line quantitative analysis of pharmaceutical granules in a V-blender. , 2014, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[6]  Bostjan Likar,et al.  Digital imaging as a process analytical technology tool for fluid-bed pellet coating process. , 2010, European Journal of Pharmaceutical Sciences.

[7]  Alvaro Realpe,et al.  Image processing and analysis for determination of concentrations of powder mixtures , 2003 .

[8]  D. T. Witte,et al.  Examples of NIR based real time release in tablet manufacturing. , 2007, Journal of pharmaceutical and biomedical analysis.

[9]  Michael K. Taylor,et al.  Monitoring Powder Blend Homogeneity Using Light-Induced Fluorescence , 2011, AAPS PharmSciTech.

[10]  Lauren Briens,et al.  Monitoring quality attributes for high-shear wet granulation with audible acoustic emissions , 2012 .

[11]  Guidance for Industry PAT — A Framework for Innovative Pharmaceutical Development , Manufacturing , and Quality Assurance , 2004 .

[12]  J. Westerhuis,et al.  Multivariate modelling of the pharmaceutical two‐step process of wet granulation and tableting with multiblock partial least squares , 1997 .

[13]  C Vervaet,et al.  Near infrared and Raman spectroscopy for the in-process monitoring of pharmaceutical production processes. , 2011, International journal of pharmaceutics.

[14]  D. Ely,et al.  An investigation into low dose blend uniformity and segregation determination using NIR spectroscopy , 2006 .

[15]  Jörg Henseler,et al.  Handbook of Partial Least Squares: Concepts, Methods and Applications , 2010 .

[16]  Manish H. Bharati,et al.  Multivariate image analysis for process monitoring and control , 2001, SPIE Optics East.

[17]  Håkan Wikström,et al.  On-Line Content Uniformity Determination of Tablets Using Low-Resolution Raman Spectroscopy , 2006, Applied spectroscopy.

[18]  G. K. Raju,et al.  Real time and noninvasive monitoring of dry powder blend homogeneity , 2001 .

[19]  Johannes G Khinast,et al.  PAT for tableting: inline monitoring of API and excipients via NIR spectroscopy. , 2014, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[20]  J. Macgregor,et al.  Analysis of multiblock and hierarchical PCA and PLS models , 1998 .

[21]  Kei Miyanami,et al.  Image processing for on-line monitoring of granule size distribution and shape in fluidized bed granulation , 1995 .

[22]  J. Percy,et al.  Quantitative photoacoustic spectroscopy of propranolol/magnesium carbonate powder mixtures in the ultraviolet and the near-infrared regions , 1981 .

[23]  Reginald B. H. Tan,et al.  Monitoring Granulation Rate Processes Using Three PAT Tools in a Pilot-Scale Fluidized Bed , 2008, AAPS PharmSciTech.

[24]  Reg Freeman,et al.  Measuring the flow properties of consolidated, conditioned and aerated powders — A comparative study using a powder rheometer and a rotational shear cell , 2007 .

[25]  Myrtille Vivien,et al.  Generalized orthogonal multiple co‐inertia analysis(–PLS): new multiblock component and regression methods , 2003 .

[26]  R. Gosselin,et al.  Monitoring the concentration of flowing pharmaceutical powders in a tableting feed frame , 2017, Pharmaceutical development and technology.

[27]  Xiaorong He,et al.  Assessing powder segregation potential by near infrared (NIR) spectroscopy and correlating segregation tendency to tabletting performance , 2013 .

[28]  Kaur Harbir PROCESSING TECHNOLOGIES FOR PHARMACEUTICAL TABLETS : A REVIEW , 2012 .

[29]  Salvador García-Muñoz,et al.  Coating uniformity assessment for colored immediate release tablets using multivariate image analysis. , 2010, International journal of pharmaceutics.

[30]  Manish H. Bharati,et al.  Multivariate image analysis for real-time process monitoring and control , 1997 .