Granulation sèche des poudres : Influence des paramètres du procédé

National audienceDans un but d'optimisation du procédé de granulation sèche de poudres, une presse à rouleaux instrumentée a été développée. Une première campagne d'essais a permis de visualiser le profil des contraintes à la surface des rouleaux en fonction de l'angle de rotation, ainsi que l'allure des différents paramètres (couple, effort, entrefer) au cours de l'essai

Compressibilité et cohésion de produits pharmaceutiques. Etude et modélisation du comportement de mélanges binaires.

216 pagesNo English abstractCes recherches ont pour objet d'améliorer la compréhension des phénomès de densification de poudres pharmaceutiques. Différents modèles ont été développés pour permettre d'expliquer les variations de propriétés des compacts (porosité, surface spécifique et résistance à la rupture) en fonction de paramètres opératoires (pression atteinte, durée de maintien sous pression). Les études menées sur le comportement des produits purs sont étendues à des mélanges binaires pour lesquels des lois de mélange originales sont décrites. Les modèles ont été validés sur différents excipients (lactose, saccharose, polyvinylpyrrolidone) et sur des principes actifs à base de kétoprofène. L'influence des paramètres morphologiques (taille des grains) et structuraux sur les propriétés precitées ont été mises en evidence

Modelling to understand porosity and specific surface area changes during tabletting

International audienceThis study presents the porosity and corresponding specific surface area evolution of pharmaceutical tablets vs. compaction pressure. A model based on quasi-chemical treatments and population balances is proposed to understand these evolutions. The main phenomena, namely fragmentation and plastic deformation, which occur in pharmaceutical powder compaction, are taken into account to explain the conjugate evolution of these macroscopic properties. These phenomena are quantified through the different parameters of the model. Experimental results on tablettose, saccharose and ketoprofen tablets show a fair agreement with theoretical results, and allow us to classify the fragmentation and the plastic deformation abilities of the products

Modélisation de l'évolution de la porosité de poudres pharmaceutiques comprimées (= Modeling of the porosity of pharmaceutical powders)

International audienceLes principaux phénomènes rencontrés dans le domaine de la compression des poudres sont le réarrangement granulaire, la fragmentation et la déformation plastique. Des modèles dans la littérature permettent de décrire l'évolution de certaines propriétés physiques, et notamment la diminution de porosité de milieux consolidés en fonction de la pression appliquée. Mais ces modèles ne rendent pas bien compte de cette évolution de porosité, aussi une nouvelle approche fondée sur une analogie quasi-chimique est proposée pour mieux quantifier ce phénomène. L'expression de la porosité incluant une porosité intragranulaire éventuelle comporte seulement deux paramètres, exprimant respectivement l'aptitude d'une poudre à être compressée et la complexité du mécanisme de réarrangement. Les résultats théoriques présentent d'excellentes corrélations avec les résultats expérimentaux obtenus dans le cas d'un principe actif, le kétoprofène, et d'un excipient pharmaceutique, le lactose

Evolution and modelling of compacted binary mixture porosity. Application to pharmaceutical tablets

National audienceThe purpose of this work consists in following physical property variations in relation with geometrical textural parameters during pharmaceutical component compaction. Models are developed to explain porosity variations of granular media submitted to increasing uniaxial pressure. These models are based on reaction mechanisms analogous to these presented in quasi chemical descriptions. Vacancy annihilation occurring when pressure increases is studied in two cases (with or without internal grain porosity). Reaction mechanisms describing different granular rearrangement phenomena are proposed. The behaviour of pure compounds as well as that of binary mixtures are studied from a theoretical point of view, and the model results proposed in this case are compared with the ones derived from experiments. In particular mixtures of one excipient, lactose, and one active principle, ketoprofen, are analysed in order to estimate porosity evolution of such mixtures, and determine mixture effects on tablet properties. The prediction limits which could be done by mixture models giving an expected behaviour starting from pure components only are discussed

Dry granulation of organic powders-dependence of pressure 2D-distribution on different process parameters

International audienceNowadays dry granulation of powders has become a very important research topic because it is the most economic way of granulation, making the particle handling easier, and avoiding the loss of material during particle processing, or particle transfers. This kind of process has been deeply studied but a better knowledge appears necessary to control the great number of parameters of the process. This is particularly important in cases where the nature of the powder may lead to very complex phenomena during compaction. In order to try and optimise dry granulation process for organic compounds, a roll press has been designed with a series of instruments enabling to control the compaction process. The apparatus consists of three parts: a vertical container with rotating steel blades avoiding arches into which the powder is poured, a feeder transferring the powder towards the rolls; the feeder is equipped with an horizontal helical screw in a cylindrical draft tube (10 mm in internal diameter, 500 mm long) and in the end of the feeder, a junction allows the change from the cylindrical symmetry of the feeder to the prismatic symmetry existing in the roll gap. The roll press (0-500 kN, load per unit length 0- 10exp4kNm-1) has been developed to record different major classical parameters: the roll speed, the roll gap, the press strength, the rotation angle, and the feeding rate (between 0 and 20gs-1). In comparison with different kinds of roll press described in the literature, in this work an original instrumentation system has been developed to catch specific data. The 3D-pressure distribution profiles at the interface between powder and the roll wall and the drive torque applied to the rolls were measured. A large-sized smooth steel-made roll (240 mm diameter, 50 mm width) has been chosen to compare the results to the industrial scale. The results obtained with an organic compound exhibited the dependence--sometimes unexpected--of the rotation angle, the feeding and the rotation speed on the pressure distribution, the roll width, and the drive torque