A Micromechanical Model of Hardening, Rate Sensitivity and Thermal Softening in BCC Single Crystals

The present paper is concerned with the development of a micromechanical model of the hardening, rate-sensitivity and thermal softening of bcc crystals. In formulating the model we specifically consider the following unit processes: double-kink formation and thermally activated motion of kinks; the close-range interactions between primary and forest dislocations, leading to the formation of jogs; the percolation motion of dislocations through a random array of forest dislocations introducing short-range obstacles of different strengths; dislocation multiplication due to breeding by double cross-slip; and dislocation pair annihilation. The model is found to capture salient features of the behavior of Ta crystals such as: the dependence of the initial yield point on temperature and strain rate; the presence of a marked stage I of easy glide, specially at low temperatures and high strain rates; the sharp onset of stage II hardening and its tendency to shift towards lower strains, and eventually disappear, as the temperature increases or the strain rate decreases; the parabolic stage II hardening at low strain rates or high temperatures; the stage II softening at high strain rates or low temperatures; the trend towards saturation at high strains; the temperature and strain-rate dependence of the saturation stress; and the orientation dependence of the hardening rate.Comment: 27 pages (LaTeX) and 15 Figures (jpg

Feasibility study of terahertz time-domain measurement to monitor individual layer thickness of bilayer tablets

Individual layer weight control is a critical issue for bilayer tablets during manufacturing process. Despite its importance for ensuring product content uniformity, few studies have investigated the possibility of developing a process analytical technology (PAT) tool to monitor the individual layer control. We introduced the use of Terahertz time-domain measurement because of its fast measurement to be inline/online. Its feasibility was then investigated to measure individual layer thickness for bilayer tablets. The design of experiment included API concentration, excipient type, and layer weight ratio. Tablets were scanned in Terahertz region and refractive index was measured. The predicted values from the measurement were compared to the reference. This study has shown that successful measurements are statistically consistent with the reference for each individual layer and accuracy can be even higher if measurements were taken both sides. Measurement failure scenario is also presented. Based on results, the potential possibility for Terahertz time-domain measurement to be a PAT tool for bilayer tablets is discussed

Optimum drug dissolution time in an intermediate compression associated with different competing water penetration mechanisms

Tablets of different composition of microcrystalline cellulose/a-monohydrate lactose and fixed drug (Acetaminophen) concentration are compressed in a rotary tablet press replicator at different compaction forces. Tablets are formulated to act as immediate release (IR) drug delivery system. Performance of IR tablets is usually controlled by the dynamics of solvent penetration into the tablet through competing mechanisms: capillarity, diffusion, and swelling/diffusion sometimes called case 2 diffusion, inducing matrix swelling. We design a device to measure tablet deformation dynamics and mass of liquid uptake simultaneously when a tablet is put in contact with a liquid through its bottom surface. On the other hand, dissolution profiles are measured in a standard USP II apparatus. Dissolution profiles present a nonmonotonic behavior with compression: the active dissolves relatively slowly when tablets are compressed below a certain threshold. Above the threshold, the dissolution rate decreases as expected due to decrease in porosity. Swelling and water uptake rates present the same nonmonotonic behavior with compression than dissolution profiles, indicating a very good correlation between them. This implies that the methodology may be used not only as a research tool and for quality by design development of tablets, but also for fast assessments in quality control environment. We finally demonstrate that a different mechanism for water penetration in the tablet is in place for differently compressed tablets: interparticle pore capillarity and swelling assisted uptake, respectively. We decoupled the two mechanisms by comparing dynamics of water versus a nonswelling liquid uptake. We postulate that the different mechanism for water uptake is responsible for the nonmonotonic behavior and the optimum dissolution rate

The role of particle size distribution on compaction and tensile strength of pharmaceutical powders

The effect of particle size distribution on compaction of powders and tensile strength of the compacted powders was investigated for microcrystalline cellulose and lactose monohydrate powders. Several samples were prepared by removing portion of the fine particles from the initial particle size distribution of the powders. The powders were compacted to form tablets and the tensile strength of the tablets was measured. Removing the fine particles showed no effect on the compaction force and tensile strength of the two powders. However, smaller initial relative density was observed for powders with larger particle size. Although the different samples initially had different relative density, the relative density approached the same value for the different samples as the compaction force was increased. These results indicate that the particle size distribution affects the flow of powders but not the mechanical properties of tablets