<abstract xmlns="http://www.w3.org/1999/xhtml"><p> The article describes the development and production of tablets using direct compression of powder mixtures. The aim was to describe the impact of filler particle size and the time of lubricant addition during mixing on content uniformity according to the Good Manufacturing Practice (GMP) process validation requirements. Processes are regulated by complex directives, forcing the producers to validate, using sophisticated methods, the content uniformity of intermediates as well as final products. Cutting down of production time and material, shortening of analyses, and fast and reliable statistic evaluation of results can reduce the final price without affecting product quality. The manufacturing process of directly compressed tablets containing the low dose active pharmaceutical ingredient (API) warfarin, with content uniformity passing validation criteria, is used as a model example. Statistic methods have proved that the manufacturing process is reproducible. Methods suitable for elucidation of various properties of the final blend, e.g., measurement of electrostatic charge by Faraday pail and evaluation of mutual influences of researched variables by partial least square (PLS) regression, were used. Using these methods, it was proved that the filler with higher particle size increased the content uniformity of both blends and the ensuing tablets. Addition of the lubricant, magnesium stearate, during the blending process improved the content uniformity of blends containing the filler with larger particles. This seems to be caused by reduced sampling error due to the suppression of electrostatic charge.</p></abstract>

The article describes the development and production of tablets using direct compression of powder mixtures. The aim was to describe the impact of filler particle size and the time of lubricant addition during mixing on content uniformity according to the Good Manufacturing Practice (GMP) process validation requirements. Processes are regulated by complex directives, forcing the producers to validate, using sophisticated methods, the content uniformity of intermediates as well as final products. Cutting down of production time and material, shortening of analyses, and fast and reliable statistic evaluation of results can reduce the final price without affecting product quality. The manufacturing process of directly compressed tablets containing the low dose active pharmaceutical ingredient (API) warfarin, with content uniformity passing validation criteria, is used as a model example. Statistic methods have proved that the manufacturing process is reproducible. Methods suitable for elucidation of various properties of the final blend, e.g., measurement of electrostatic charge by Faraday pail and evaluation of mutual influences of researched variables by partial least square (PLS) regression, were used. Using these methods, it was proved that the filler with higher particle size increased the content uniformity of both blends and the ensuing tablets. Addition of the lubricant, magnesium stearate, during the blending process improved the content uniformity of blends containing the filler with larger particles. This seems to be caused by reduced sampling error due to the suppression of electrostatic charge.

Influence of Process Parameters on Content Uniformity of a Low Dose Active Pharmaceutical Ingredient in a Tablet Formulation According to GMP

Department of Pharmaceutics Faculty of Pharmacy University of Veterinary and Pharmaceutical Sciences 612 42 Brno, Czech Republic

Masaryk Memorial Cancer Institute 61242 Brno, Czech Republic

Acta Pharmaceutica

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

The article describes the development and production of tablets using direct compression of powder mixtures. The aim was to describe the impact of filler...

Influence of Process Parameters on Content Uniformity of a Low Dose Active Pharmaceutical Ingredient in a Tablet Formulation According to GMP

Published Online: Oct 08, 2014

Page range: 355 - 367

Accepted: Apr 02, 2014

DOI: https://doi.org/10.2478/acph-2014-0022

Keywords
content uniformity, warfarin, validation, narrow therapeutic index, Faraday pail, PLS regression

© by Anna Krondlová

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Influence of Process Parameters on Content Uniformity of a Low Dose Active Pharmaceutical Ingredient in a Tablet Formulation According to GMP

Published Online: Oct 08, 2014

Page range: 355 - 367

Accepted: Apr 02, 2014

DOI: https://doi.org/10.2478/acph-2014-0022

Keywordscontent uniformity, warfarin, validation, narrow therapeutic index, Faraday pail, PLS regression

© by Anna Krondlová

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Keywords
content uniformity, warfarin, validation, narrow therapeutic index, Faraday pail, PLS regression