Mechanical approach for the understanding of capping problems (breakage) during pharmaceutical compaction. Study of the fracture behavior of tablets and of the viscoelastic and viscoplastic behavior.
Project financing
ANR
266 k€
Abstract
Tablets are the most popular pharmaceutical dosage form. They are manufactured in the industry using a die compaction process and the compacted powders have typical grain size around 100μm. Tablets must fulfill a lot of requirements. Among them, the mechanical strength is of particular importance as it makes it possible to maintain the integrity of the tablet during all the post-compaction processes (coating, etc.) until its delivery to the patient. By adjusting the process parameters, e.g. the compaction force, it is possible to obtain tablets with different porosities. Moreover, the powders used to make tablets can have very distinct mechanical behaviors. As a consequence, by changing the kind of powder and the process parameters, it is possible to obtain tablets with different apparent mechanical properties.
Moreover, a better understanding of why a tablet may break under a certain load, would also make it possible to foresee problems of capping/lamination that are among the most frequent problems encountered during the manufacture of tablets. They correspond to a sudden breakage of the tablet during its ejection from the die or during its post-compaction relaxation. Lamination corresponds to a breakage of the tablet in layers whereas capping corresponds to the separation of the top of the tablet.
The aim of this project is the study of capping (or lamination) which is a well-known problem since more than a century but still remains not fully understood. Thanks to a global approach, the goal is to identify the causes and to understand their respective contribution to the phenomenon. For this, we develop an original approach both experimental and numerical based on material and fracture mechanics. For the moment, this approach has not been fully developed in the pharmaceutical field but it is the only one that can make it possible to have a fundamental understanding of the phenomenon. This understanding can only be obtained by studying the stresses applied to the tablet during the whole compaction cycle (especially during the unloading phase) and by defining a failure criterion suited to pharmaceutical tablets. These two aspects are necessary to be able to predict the breakage of the tablet as a function of the applied stresses.
This project is separated into two parts that will be developed simultaneously. In the first part, we would like to work on the mechanical models that are used to describe the behavior of the tablet during FEM modelling. An improvement of these models is necessary to make it possible to obtain, in the FEM simulations, stress distributions quantitatively realistic. For this purpose, time dependent properties like viscoelasticity and viscoplasticity (that are not taken into account until now) must be characterized, modeled and implemented in a finite element method (FEM) code. Non-linear elasticity for high elastic deformations will also be studied.
The other part of this project deals with the definition of a failure criterion for pharmaceutical tablets to be able to predict the failure under a certain load. Two approaches will be developed. The first one will be to define a failure criteria taking into account the stress distribution especially in the case of local stress concentrations. The second one will use the formalism of fracture mechanics in order to define a criteria based on fracture energy.
