Mass Uniformity: Influence of Operational Compression Conditions on Breakability of Scored Tablets as Part of Manufacturing Robustness Evaluation
BART DE SPIEGELEER1*, LIEVEN VAN VOOREN2, THOMAS THONISSEN1, PHILIPPE JOYE1, BART CORNELISSEN1, GEERT LAMMENS2 AND GUIDO SLEGERS1
1. Ghent University (UG), Faculty of Pharmaceutical Sciences, Department of Pharmaceutical Analysis, Harelbekestraat 72, 9000 Gent, Belgium
2. Health Engineering and Assurance (HEA), Keizer Karelstraat 175, 9000 Gent, Belgium
(Received: September 17, 2004; Accepted: November 1, 2004)
ABSTRACT
Dose uniformity is a key quality element of drugs. The purpose of this study was to demonstrate a practical approach to evaluate the breakability robustness as part of the tabletting validation of a scored tablet. The influence of operational compression parameters (speed and force) on the weight variabilities of half- and quarter-tablets was investigated using two types of cross-scored round tablets of identical composition but different in size. It was shown for the used veterinary model tablet that manufacturing variation of two compression parameters around the defined target values do not significantly influence the weight variability of the broken tablets. The empirical guidance was also confirmed that for the investigated dose-proportional tablets the standard deviation of the broken tabletpart weight is linearly related to the original tablet weight. There exists a strong correlation between the variability of half-tablets and of quarter-tablets: the theoretical model previously presented was refined, demonstrating that the additional variance induced by breaking is a linear function of the break-line length. As a consequence, the standard deviation of half- and quarter-parts of crossscored round tablets, expressed in mass units, will thus remain approximately identical. Hence, the relative standard deviation (RSD) of
quarter-tablet weights will nearly double when breaking half-tablets into quarter-tablets.
Key words: scored tablets, tablet breakability, weight uniformity, statistical control, compression validation, robustness development