A new theoretical approach to tablet strength of a binary mixture consisting of a well and a poorly compactable substance.

The objective of this study was to analyse the tensile strength of a well and a poorly compactable substance in a tablet mixture. Recent developments in the theory of percolation were taken into account and two power laws are proposed, one for the tensile strength as a function of the relative density of the mixture, and the other for the relationship between the strength and compaction pressure. Both equations are assumed to be valid in a comparatively low pressure range. A universal testing instrument Zwick UPM 1478 was used for the manufacture and testing of the compacts. Mixtures of Avicel PH101 and paracetamol at different ratios were chosen as model systems. The experimental results showed that the proposed model equations fitted the experimental data reasonably well for all mixture ratios. It was observed that the critical solid fraction of the mixture, i.e. the strength percolation threshold, increased with rising amounts of the drug. We investigated the strength threshold not only in terms of the solid fraction, but also in terms of the mass fraction (excipient percolation threshold). It is assumed that a tablet can only be produced with a certain minimal amount of the well compactable substance that is needed to build a percolating cluster in the tablet. An interpretation is therefore provided for the dilution capacity of a direct tableting excipient with a poorly compactable drug. The dilution capacity was experimentally determined according to the method of Minchom and Armstrong (Br. Pharm. Conf. (1987) 69 pp.). Our experimental estimate of 79.9% drug is in perfect agreement with our proposed theoretical calculation of 79.7%. These estimates are, however, much higher than the one reported in a recent study (Y. Habib, L. Augsburger, G. Reier, Th. Wheatley, R. Shangraw, Dilution potential: a new perspective, Pharm. Dev. Tech. 1 (2) (1996) 205-212) where the dilution capacity of the same mixture was investigated. This discrepancy can be explained based on the different pressure ranges and extrapolation techniques that were used. As a conclusion, concepts of the percolation theory can successfully be applied to the kind of mixture studied in this paper. It is conceivable that the theoretical tools presented can also be applied to mixtures of more than two substances if they consist of a single well compactable excipient and several poorly compactable components. Such mixtures are relevant for the development of direct compressible tableting formulations.