Investigation and modelling approach of the mechanical properties of compacts made with binary mixtures of pharmaceutical excipients.

Three pharmaceutical excipients (microcrystalline cellulose, lactose, anhydrous calcium phosphate) and their binary mixtures were compacted to form compacts of various mean porosities. Some mechanical properties (Young's modulus, tensile strength and Brinell hardness) were studied on these compacts. The mechanical properties of the binary mixtures were not proportional to the mixture composition expressed in mass. More, for all the properties, a negative deviation was always observed from this linear relationship. In reference to a composition percolation phenomenon, critical mass fractions were detected from the graph mechanical property vs. mass composition of a mixture. The results obtained with Brinell hardness differed from the results of the Young's modulus and the tensile strength, i.e. the most plastic material in the binary mixture controlled the mixture behaviour. Secondly, a predictive model based on a statistical approach was proposed for the Young's modulus and the tensile strength. The validity of this model was verified on experimental data, and an interaction parameter used to characterize the affinity of the two compounds was calculated. Finally, the X-ray tomography technique was applied to the compacts of cellulose/phosphate mixtures to obtain cross-sections images of the compacts. The analysis of the cross-sections images allowed explaining the no linear relationship of the different mechanical properties results observed on these binary mixtures.

Compaction behaviour and new predictive approach to the compressibility of binary mixtures of pharmaceutical excipients.

The compressibility of three pharmaceutical excipients (microcrystalline cellulose, lactose and anhydrous calcium phosphate) and their binary mixtures was studied. The aim of this work was to observe the impact of the mass composition of the mixture on the compressibility. The single-compound materials and their mixtures were compacted using instrumented presses. It allowed obtaining compression cycles (i.e., force-displacement curves) which were associated with energy measurements (specific compaction energy, Esp cp and specific expansion energy, Esp exp). It was observed that for the mixtures studied, the change of Esp cp with the mass composition could be fitted using a linear relationship (it was not the case with Esp exp). A linear relationship between the porosity of mixture's compacts and the mass composition was also obtained. Heckel's plots were then obtained for the three excipients and the mixtures. The mean yield pressure was calculated with the "in-die-method" and the "out-of-die method". A proportional relationship was not valid for the mean yield pressures. But, a predictive approach was proposed in order to obtain indirectly the mean yield pressure of a binary mixture if the data of the single materials were known. It used the linear mixing rule observed with the porosity. The validity was verified and compared with the experimental values. This comparison showed that it was possible to predict the mean yield pressure of binary mixtures from the accessible data of the single excipients.

Stress fluctuations and macroscopic stick-slip in granular materials.

This paper deals with the quasi-static regime of deformation of granular matter. It investigates the size of the Representative Elementary Volume (REV), which is the minimum packing size above which the macroscopic mechanical behaviour of granular materials can be defined from averaging. The first part uses typical results from recent literature and finds that the minimum REV contains in general 10 grains; this result holds true either for most experiments or for Discrete Element Method (DEM) simulation. This appears to be quite small. However, the second part gives a counterexample, which has been found when investigating uniaxial compression of glass spheres which exhibit stick-slip; we show in this case that the minimum REV becomes 10(7) grains. This makes the system not computable by DEM. Moreover, similarity between the Richter law of seism and the exponential statistics of stick-slip is stressed.

Magnetic resonance imaging investigation of the mixing-segregation process in a pharmaceutical blender.

Magnetic Resonance Imaging (MRI) was used to study the mixing process of binary mixtures of free flowing sugar beads in a Turbula mixer. In order to make particles MRI-sensitive, some reference beads were doped with an organic oil. Doped and undoped particles were mixed and MRI was used to non-destructively image the particle bed for a given number of mixer rotations (NR), bead diameter ratio (R=d(ref)/d(i)) and rotation speed (V). All the results were quantified on the basis of image analysis to characterise the degree of mixing. Studies showed that for binary mixtures of identical particle size, the mixing was complete after 30 rotations, whereas for beads of different size (R=2.8) a segregated steady state was obtained after nearly 10 rotations. Experiments revealed that segregation appeared as soon as R=0.9. Moreover, the lower the rotation speed, the more segregated the final state was. It appeared that for a filling level greater than 80%, dead regions appeared in the centre of the powder bed. In conclusion, when the particles are non-cohesive, the Turbula blender perfectly mixes identical beads but segregation occurs for beads of different size after just a few rotations.

Frictional-collisional regime for granular suspension flows down an inclined channel

Here granular suspensions refer to very concentrated suspensions of particles within a Newtonian fluid. Under certain conditions given in the paper, the bulk stresses mainly result from the combination of frictional and collisional interactions at the particle scale. The corresponding flow regime is called the frictional-collisional regime. The constitutive equation adapted to this regime is not well known. We propose a constitutive model based on the balance between frictional and collisional interactions. We have applied this model to granular flow down an inclined channel. It is shown that the mass flow rate is proportional to the flow depth.

Frozen wave induced by high frequency horizontal vibrations on a CO2 liquid-gas interface near the critical point.

We used the liquid-vapor equilibrium of CO2 near its critical point (T(C)-T=1 to 150 mK) in order to study the stability of an interface between a gas and a liquid having close densities rho(L) approximately rho(V) when submitted to high frequency f (3-57.5 Hz) horizontal vibrations (of amplitude a from 0.1 to 2.5 mm). Above a given velocity threshold (2piaf )(0) we observed a "frozen wave," corresponding to an interface profile of sinelike shape which is stationary in the reference frame of the vibrated sample cell. By varying the vibration parameters, the surface tension, and the density difference between the two phases via the temperature, it was found that the wavelength and the amplitude of the stationary profile are both increasing functions of the frequency and of the amplitude of the vibration and that they are proportional to the capillary length. Our measurements are consistent with a model of inviscid and incompressible flow averaging the effect of the vibration over a period and leading to a Kelvin-Helmholtz-like instability mechanism due to the relative motion of the two fluids.

Stress in conic piles determined by a centrifuge experiment: breakdown of scaling hypothesis.

It is found experimentally that vertical-stress field in a conic pile depends on gravity level, building process, and loading story. For instance, a conic pile with inclined strata does exhibit a minimum of stress in the center, whereas conic pile with horizontal strata does not; both piles exhibit an arching effect, which increases with gravity. This questions the assumptions of radius stress field scaling. Amplitude of the stress dip is found to be 10%, which is much smaller than what was found in previous experiments.

Modeling of stress distribution in granular piles: Comparison with centrifuge experiments.

The classical method to compute stress and strain distributions in granular materials is recalled using continuum mechanics approach, and different rheological laws described. It is recalled that granular materials exhibit highly nonlinear response such as nonlinear elasticity, dilatancy and plastic flow. Finite element technique is used to predict the stress field distribution below a conic and a triangular pile. The dependence of the stress distribution on the rheological law, the bottom boundary condition and the building process (horizontal or inclined strata) is demonstrated. These results are compared to experimental data obtained in centrifuge. (c) 1999 American Institute of Physics.