A.C. Bentham

Numerical Simulation on Pharmaceutical Powder Compaction

In this paper, we present a modified density-dependent Drucker-Prager Cap (DPC) model with a nonlinear elasticity law developed to describe the compaction behavior of pharmaceutical powders. The model is implemented in ABAQUS with a user subroutine. Using microcrystalline cellulose (MCC) Avicel PH101 as an example, the modified DPC model is calibrated and used for finite element simulations of uniaxial single-ended compaction in a cylindrical die. To validate the proposed model, finite element simulation results of powder compaction are compared with experimental results. It was found that finite element analyses gave a good prediction of both the loading-unloading curves during powder compaction and the compaction force required for making a tablet with a specified density. Further, the failure mechanisms of chipping, lamination and capping during tabletting are investigated by analysing the stress and density distributions of powders during the three different phases of the tabletting processes, i.e. compression, decompression and ejection. The results indicate that the model has excellent potential to describe the compaction process for generic pharmaceutical powders.

Analysis of Failure Mechanisms during Powder Compaction

Powder compaction is a well-established process for manufacturing a wide range of products, including engineering components and pharmaceutical tablets. During powder compaction, the compacts (green bodies or tablets) produced need to sustain their integrity during the process and possess certain strength. Any defects are hence not tolerable during the production. Therefore, understanding failure mechanisms during powder compaction is of practical significance. In this paper, the mechanisms for one typical failure, capping, during the compaction of pharmaceutical powders were explored. Both experimental and numerical investigations were performed. For the experimental study, an instrumented hydraulic press (a compaction simulator) with an instrumented die has been used, which enable the material properties to be extracted for real pharmaceutical powders. Close attentions have been paid to the occurrence of capping during the compaction. An X-ray Computed Microtomography system has also used to examine the internal failure patterns of the tablets produced. Finite element (FE) methods have also been used to analyse the powder compaction. The experimental and numerical studies have shown that the shear bands developed at the early stage of unloading appear to be responsible for the occurrence of capping. It has also been found that the capping patterns depend on the compact shape.

Granular templating: Effects of boundary structure on particle packings under simultaneous shear and compression

We present our findings on the effect of various confining substrates, both crystalline and amorphous, on spherical particles, packed under gravity followed by the simultaneous application of shear and compressive strains. We treat the voids and particles of the substrates interchangeably by identifying the primitive unit cell for each, and use radial and angular distribution functions to determine the packing structures. We show that a substrate templated with a 2D square lattice, for which void and particle packing structures are identical, is most suitable for inducing crystallisation mimicking the substrate structure.

Mapping powder flow behaviour at different pharmaceutical processing stage

(86%) (Sigma-Aldrich, UK) (Chidavaenzi et al 1997). The anomeric composition of crystalline and amorphous lactose was determined by Gas Chromatography (Dwiwedi & Mitchell 1989). Solution calorimetry data were collected as described by (Hogan & Buckton 2000). Partially amorphous samples were prepared by directly weighing proportional masses of crystalline and amorphous lactose (prepared from that crystalline batch) into glass-crushing ampoules. The mass of the crystalline component was kept constant in all the mixtures (200 0.01mg) and an appropriate amount of spray-dried material was added to make 1, 3 and 5% amorphous samples. In the same way, in the perfusion experiments the 1, 3 and 5% amorphous samples were directly prepared into the calorimetric ampoule, using 50 0.01mg of the crystalline component. Calorimetric data were recorded using a 2277 Thermal Activity Monitor (TAM; Thermometric AB, Sweden) at 25 C equipped with a gas perfusion unit. The following RH programme was used: 0% for 5 h, 95% for 15 h and 0% for 5 h. The determined enthalpies of solution and crystallisation for each of the analysed samples are shown in Table 1. For the perfusion data, the samples prepared from -lactose returned a higher heat output, which could have been due to mutarotation of -lactose to -lactose. On the solution calorimetry experiments samples prepared from -lactose monohydrate returned a higher enthalpy of solution, as -lactose monohydrate exhibits a higher enthalpy of solution than -lactose. Calibration curves were constructed by plotting the heat of crystallisation and solution versus the known amorphous content. Due to the differences in the measured enthalpies for the different samples, the calibration curves were shown to be significantly different for the two batches, for each of the techniques. Thus it is shown that quantification of the amorphous content of a processed sample of unknown anomeric composition would be problematic, unless the calibration curve is prepared from the same batch of material as the processed sample.