Press-coated tablets are a type of pharmaceutical tablets intended to release an active substance in the body, with a delay after the administration, called lag-time, and with defined release kinetics. These tablets belong ...
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Press-coated tablets are a type of pharmaceutical tablets intended to release an active substance in the body, with a delay after the administration, called lag-time, and with defined release kinetics. These tablets belong to the delayed-release pharmaceutical forms, which are used, among other things, to treat diseases with nocturnal symptoms. These features are achieved through a core/shell structure, where the core contains the active substance. Press-coated tablets are produced by two compactions of pharmaceutical powders. Firstly, the core tablet is manufactured by conventional die-compaction, and secondly, a solid shell is formed around it during coating compression, carried out with a powder containing no active ingredient. Many of the works have studied ways to control the lag-time by modifying the formulation of the core and the shell, with excipients accelerating or delaying the release. However, relatively little work has been done on the coating compression process itself. Nevertheless, this process is very particular compared to a simple compression, and could be at the origin of an atypical structure of the tablet, with major effects on its final properties.This work aims to study in detail the distribution of mechanical stresses occurring during coating compression, and their effects on the structure of the shell and the core. Through coating compression experiments coupled with finite element numerical simulations, it has been shown that the layers of powder directly above the core become very dense compared to the rest of the shell. This results in a highly concentrated axial stress on the core, consequently changing its dimensions and reducing its relative density at low apparent pressure. This effect is even more marked when the layer thickness is low, which makes this parameter a new parameter of interest in the design of press-coated tablets. The thickness of the band, determined by the choice of the punches, also plays a role in the distribution of the stresses, and this results in a difference in density between the band and the layers of the envelope that is greater with a low band thickness.This heterogeneous structure of the shell and the difference in mechanical properties with the core have consequences on the outcome of the diametral test, which is the main test for the mechanical strength performed on the pharmaceutical tablets. Indeed, this test is applicable on tablets which fail diametrically, but in the case of press-coated tablets, it is shown in this work that the rupture profile can be of four different types. Each fracture profile reflects the resistance of a different zone and is dependent on the stiffness of the different regions of the tablet, which was studied through an experimental and numerical approach. These conclusions question the applicability of this test for the press-coated tablets.Finally, the active release properties of press-coated tablets were studied according to the process parameters. A strong dependence on compression pressure and dimensions was shown. In particular, a high lag-time is favoured by a high thickness of the band and, to a lesser extent, of the layer. This shows the interest of taking into account these two geometric parameters during development. The different structures due to these parameters have not only an effect on the lag-time, but also on the opening mode during the dissolution test. This therefore results in rapid or slow dissolution kinetics after the lag-time, depending on the manufacturing parameters of the tablets.
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