Controlling the lag-time and release kinetics of press-coated tablets using process parameters and tablet geometry.

Press-coated tablets are an advantageous technology to achieve delayed releases of active ingredients. They are characterized by a core-shell structure, that makes it possible to tune the lag-time and release kinetics in order to meet the chronotherapeutical goals. Thus, these features are the most important quality attributes to be controlled when designing a press-coated tablet. Many studies have focused on the influence of the formulation on the release attributes. This work aims to study the influence of geometrical and process parameters on the release attributes of press-coated tablets, while keeping a constant formulation. In particular, the variation of compression pressure, layer thickness and band thickness made it possible to vary the lag-time from 1 h to 10 h. These parameters also have an influence on the release kinetics after the lag-time. Indeed, two main opening modes were observed during the dissolution test that correspond to fast or slow release rates. The opening mode obtained depends on the density distribution in the shell, which is directly influenced by the process parameters.

Influence of the punch shape on the core and shell structure of press-coated tablets.

Press-coated tablets are a key technology to achieve delayed releases in chronotherapeutics. The drug release properties of this kind of tablets are linked to its unique core-shell structure. It is thus important to understand the influence of the process parameters on this structure. As different shapes can be used in the industry, we focused, in this study, on understanding the influence of punch shape on the final structure of a press-coated tablet. Experiments were performed using flat, bevel-edged and concave punches for the coating-compression to study the effect of the punch shape on the final properties of the core but also on the density distribution in the shell. The experiments were supported by numerical simulation to understand the mechanical effects in the powder compression process. It was found that the radial and axial stress state in the shell and in the core during compression is very dependent on the punch shape. The use of concave punches results in a more hydrostatic stress state compared to flat punches. The consequences on the structure are a more homogenous shell and less deformation of the core, which confirms that the tooling shape is a critical parameter to consider for the production of press-coated tablets.

Breaking patterns of press-coated tablets during the diametral compression test: Influence of the product, geometry and process parameters.

Press-coated tablets are a high-interest technology in chronopharmaceutics, for modified release applications. As for any kind of tablet, the test of the mechanical resistance is of primary importance at the industrial level during both the development and production steps. For this purpose, the diametral compression test is commonly used in the industry for press-coated tablets. Nevertheless, the result of this test can be much more complex compared to the case of single layer tablets. This work aims to study the applicability of this test to press-coated tablets. Diametral compression tests were performed on press-coated tablets obtained with different products (shell/core), shell sizes and compaction pressures. Four types of breaking profiles were found: total diametral, shell diametral, around the core and laminated depending on the process parameters/products used to obtain the tablet. Digital image correlation was used in order to understand the breaking patterns especially in terms of failure initiation and propagation. The kind of breaking pattern obtained is dependent on the final structure of the tablet in terms of density distribution and thus of elastic properties. To confirm the findings, numerical simulations by the finite element method was used to visualize the stress distribution inside the tablet and confirm the influence of the process parameters. The multiple failure profiles obtained imply that the output value of the diametral compression test applied to press-coated tablets should be taken with caution.

Effect of the compaction parameters on the final structure and properties of a press-coated tablet (Tab-in-Tab): Experimental and numerical study of the influence of core and shell dimensions.

With increasing interest in chronopharmaceutics, press-coated tablets have become a key technology in the field of modified release drug delivery systems. Although their benefits in terms of drug release have been largely studied, the comprehension of the compaction process of press-coated tablets is yet to complete. Particularly, the effects of geometrical parameters like the ratios between the thickness/diameter of the core and the thickness/diameter of the whole tablet were so far not much considered. Moreover, there is only few studies in the literature about the effect of the press-coating compression on the final structure and properties of the core. The present work consists in a joint experimental and numerical study that aims to assess these points. The study revealed high stress concentrations on the core during compression, causing high permanent deformations of the core, especially when the ratio between the core thickness and the total tablet thickness was high. The mechanical properties of the core tablet were also shown to be impacted: its density and strength were found to decrease before increasing again along the coating-compression. This effect was highlighted to be dependent on the triaxiality of the stress state (i.e. the ratio between the stresses in the different directions), itself depending on the two studied geometrical parameters. As the properties of the core affect the release attributes, ratios between the dimensions of the core and the dimensions of the whole tablet (thickness, diameter) should be taken into account as critical parameters for the manufacture of press-coated tablets.