Caratterizzazione del processo di compressione di materiali farmaceutici: approcci empirici e reologici.

Tablets, the most widely used pharmaceutical dosage form, are prepared by the compression process through which two punches exert pressure on mixtures of powders or granules, loaded within a confined space. Despite the apparent simplicity of the process, it is not free from problems that in some cases make it difficult to apply. In particular, the feasibility of this process is mainly related to the characteristics of the material to be compressed, such as flowability, adhesiveness and tabletability. While in the first two cases it is possible to effectively operate by the addition of suitable excipients or by introducing a further production step such as granulation, in the case of poor tabletability these solutions may not be effective in the presence of high levels of active ingredient. Low tabletability is essentially related to the rheological features of the material to be compressed and, more specifically, to a high elasticity of the material itself, which cause the production of fragile or damaged tablets (capping and lamination). Since the rheological behaviour of the materials is strictly time-dependent, these problems are more relevant by the increase of production speed and consequently they are more frequent during the production phase than in the small scale development. The analysis of compression behaviour has been a topic of interest over the years and it has been attempted to develop models that can mathematically describe this process and predict its outcome in the various materials. The first models have been developed since the 1960's. That proposed by Heckel (Trans Metal Soc Aime, 1961) is the more frequently applied. Although it has been formulated as a scientific theory, the starting point is based on an assumption that has never been verified and can therefore be considered as an empirical model. Another semi-empirical approach is that based on the calculation of compression / decompression work by force-displacement traces. In this case, the main limitation is due to the fact that some essential contributions to the definition of the various energies involved are ignored (friction and heat). In the early 1980s, the compression process began to be studied through a rheological approach. Rippie and Danielson (J Pharm Sci, 1981) were the first to attempt to define the viscoelasticity of pharmaceuticals by deriving rheological parameters directly from the compression process, while Radebaugh et al (Int J Pharm, 1989) addressed the problem by analyzing tablets through oscillatory tests. Since the mid-2000s, however, it has been attempted to develop a predictive method by linking the rheological properties of individual discrete units to be compressed with the compaction performance (Bashaiwoldu et al, Int J Pharm, 2004 and Adv Powder Technol 2011; Cespi et al, Eur J Pharm Biopharm, 2007).This last approach is the most promising though limited by the ability to perform rheological tests only when the materials consist of particles of a certain size and regular shape.