Influence of the Parameters Molecular Structure and Granularity on the Compactibility of a Powder

Abstract

The aim of this study was to determine whether it is possible to obtain better characterization of materials in order to find out if these one are suitable in Quality Assurance for direct tableting. We tried to show that a methodological approach combining chemical, physical and technological aspects could control the direct compression process. We chose orthoboric acid as a study model for the direct compression. From a chemical point of view, our findings show only one crystalline molecular structure (RX, DSC and Pycnometry) which means an homogeneous chemical system. Concerning the particular state (Sieving and Microscopic approach), granularity is very different between the two forms, “crystalline” ABC and “powder” ABP.

Technological studies show a rheological and mechanical difference, as it is demonstrated, on the one hand by the behaviour of the bulk powder (Volumenometer), on the other hand by the feasibility on the machine (Alternative EKO). We explain this difference of behaviour by only the granularity aspect. Consequently, we think that in this case, controling the granularity means controling this direct tableting process.     

Matrix tablets of carrageenans. I. A compaction study

Carrageenans can be used as excipients for controlled-release tablets. The aim of this study was to determine their compaction and consolidation behavior to prove their usefulness for tableting. The Carr indices of the three carrageenans, two κ-carrageenans (Gelcarin® GP-812 NF and GP-911 NF) and one ι-carrageenan (Gelcarin GP-379 NF), indicate that the materials are free flowing. They are polymers in the rubbery state. Their glass transition-temperature is about 0°C analyzed by differential scanning calorimetry (DSC). The powders were analyzed regarding their compression behavior using an eccentric tableting machine. From data obtained during one compaction cycle, porosity-pressure and pressure-time plots were made. Compaction behavior is evaluated by fitting the pressure-time function to the pressure-time plot and by fitting the Heckel function to the porosity-pressure plot. The polymers show “viscoelastic” tableting behavior. Several additional tableting parameters were analyzed for strengthening the results obtained, namely, maximum work, maximum power, and the time between maximum upper punch force and maximum displacement of the upper punch. The crushing strength of the tablets is high; therefore, the carrageenans are able to form strong compacts. However, they remain in the rubbery state, as shown by thermomechanical analysis. In addition, elastic recovery is regarded at several times after ejection. Finally, after 10 days, it is about 30% as determined from the minimum of tablet height during the compression cycle. These results indicate that the carrageenans are suitable tableting excipients for controlled-release tablets. They show good compactibility and good consolidation behavior. Strong compacts with a high elastic recovery are formed; this means that the materials are able to embed drugs softly. Only a little stress and strain remains in the tablet. All three carrageenans show similar tableting behavior, and a flexible dosage form design is possible.     

A fast procedure for computing the total system cost of an appointment schedule for medical and kindred facilities

Scheduling outpatients and medical operation rooms has the following structure: Nusers are given appointment times to use a facility, the duration required by the facility to service each user is stochastic. The system incurs a “user idle cost” if a user arriving at the appointed time finds the facility still engaged by preceding users, while a “facility idle cost” is incurred if the facility becomes free before the next user arrives. We develop an accurate procedure to compute the expected total system costs for any given appointment schedule. Compared to earlier related procedures, ours is much faster and can handle larger problems as well as very general service-time distributions. We then show that this fast computation procedure enables one to determine easily the “lowest-cost appointment schedule” for any given “job” (i.e., “user”) sequence. This in turn will enable one to search for the optimal job sequence that has the best “lowest-cost appointment schedule”.     

Controlled Release from Glycerol Palmito-Stearate Matrices Prepared by Dry-Heat Granulation and Compression at Elevated Temperature

Diprophylline release from glycerol palmito-stearate “precirol” matrices containing different direct compression (DC) excipients, with variable dissolving/disintegrating ability, is investigated. The matrices are formed by employing dry-heat granulation and compression at elevated temperature.

Greater drug release prolongation is achieved with the dissolving DC excipients than with the swelling ones. The release is described on the basis of two biexponential first order models and the Weibull function as well.

The effect of compression conditions (temperature and pressure) on the drug release is found to be related to the compaction behaviour of the DC excipients, i.e. plastic deformation or fragmentation.     

Mechanical behaviour of a two-phase material from the behaviour of its components: Interface modelling by finite element method

In this paper, the principle of a solution for “thermal” connection between two solids is analyzed. We shows results given by the solution applied to the mechanical behaviour of a γ/γ′ two-phase material and to “artificial” structures obtained from modern techniques for epitaxial deposit. It appears that the use of a true or fictitious thermal loading constitutes a simple “connection” procedure, but is particularly coherent with the mechanics of two-phase crystalline materials with different lattice parameters. It would be interesting to apply the model to real structures, with misfit and interfacial dislocations.     

Isothermal transformation of low-carbon microalloyed steels

The microstructures of isothermal transformation products and time–temperature–transformation (TTT) diagrams of two low-carbon microalloyed steels have been investigated by the means of dilatation and microscopy. The results show there are three independent “C-shape” curves in the TTT diagrams of low-carbon microalloyed steels, namely, the polygonal ferrite/pearlite transformation “C-shape” curve, the massive ferrite transformation “C-shape” curve and the bainitic transformation “C-shape” curve, respectively. The effects of the carbon and Mo content on massive ferritic transformation are discussed.     

Guides “bimorphes” d''ondes ultrasoniques “bimorph” ultrasonic wave guides”

An analysis of the dispersion of elastic waves is presented for two types of long ultrasonics wave-guides that we qualify of “bimorph”: (i) a “three-layer” guide made of two different materials and (ii) a “clad core” guide built up of a rectangular core surrounded by a cladding, the materials of the rod and cladding having different properties. An analytical model is proposed to describe the extensional, flexural and torsional motions in “bimorph” wave guides having two geometrical and material symmetry axes. The asymptotic behaviour of the model allows one to select the material properties which lead to modes guided essentially either in the central layer or in the core of the bimorph guide. Moreover, the dispersive properties of a “bimorph” can be controlled through the choice of geometrical and material parameters.     

Validation and calibration of a lateral confinement model for long-rod penetration at ordnance and high velocities

In designing targets for laboratory long-rod penetration tests, the question of lateral confinement often arises, “How wide should the target be to exert enough confinement?” For ceramic targets, the problem is enhanced as ceramics are usually weak in tension and therefore have less self-confinement capability. At high velocities the problem is enhanced even more as the crater radius and the extent of the plastic zone around it are larger. Recently we used the quasistatic cavity expansion model to estimate the resistance of ceramic targets and its dependence on impact velocity [1]. We validated the model by comparing it to computer simulations in which we used the same strength model. Here we use the same approach to address the problem of lateral confinement.

We solved the quasistatic cavity expansion problem in a cylinder with a finite outside radius “b” at which σ_r (b) = 0 (σ_r = radial stress component). We did this for three cases: ceramic targets, metal targets, and ceramic targets confined in a metal casing. Generally, σ_r (a) is a decreasing function of “a” (“a” = expanding cavity radius, and σ_r (a) = the stress needed to continue opening the cavity). In the usual cavity expansion problem b → ∞, σ_r (a) = const., R =−σ_r (a) (R = resistance to penetration). For finite “b” we estimate R by averaging σ_r (a) over a range o ≤ a ≤ a_r, (where a_r, the upper bound of the range, is calibrated from computer simulations).

We ran 14 computer simulations with the CTH wavecode and used the results to calibrate a_r for the different cases and to establish the overall validity of our approach.

We show that generally for D_t/D_p > 30, the degree of confinement is higher than 95% (D_t = target diameter; D_p = projectile diameter; and degree of CONFINEMENT = R/R_∞; R∞ = resistance of a laterally infinite target). We also show the tensile strength of ceramic targets (represented by the spall strength P_min) has a significant effect on the degree of confinement, while other material parameters have only a minor effect.     

A note on capacitated lot sizing with setup carry over

The “capacitated lot sizing problem with setup carry over” is based on the well known “capacitated lot sizing problem” and incorporates the possibility of preserving a setup state between successive periods. The approach at hand is to decompose the problem using Lagrangean relaxation. Subproblems are to be solved optimally employing dynamic programming techniques. Subgradient optimization guides the approach to heuristic solutions of the original problem. The present paper shows that this algorithm does not necessarily provide the optimal solution to the subproblems. The algorithm's flaw is corrected such that it allows to solve the subproblems optimally.     

Relationship Between Particle Size and Dissolution Rate of Bulk Powders and Sieving Characterized Fractions of two Qualities of Orthoboric Acid

We have carried out a study of the particle size distribution and aqueous dissolution rate of two commercially available qualities of orthoboric acid, labeled “crystal” (ABC) and “powder” (ABP). In a previous work, we have shown that the two commercial qualities of orthoboric acid chosen as model compound (“powder” and “crystal”) are related to the same crystal network in spite of their dvferent names. However, these two qualities have very different size particle distributions, as previously determined by sieving and confirmed by the present laser light scattering study. Dissolution testing is performed under sink conditions and show that the bulk ABC quality dissolves far more rapidly that the bulk ABP quality, For each quality, dissolution rates of four sieved particle size fractions (0-90 μm; 90-125 μm; 125-180 μm; 180-250 μm) were compared. Concerning the ABC quality, comparisons were also done with three other particles size fractions: 250-355 μm, 355-500 μm, and 500-710 μm. This study used the dQ/dt versus t profile. Dissolution profiles of the fractions enclosing particles with a size superior to 125 μm are very close. On the other hand, fractions enclosing particles with a size smaller than 90 μm present a different profile and a slower rate of dissolution.     

Characterization of the tableting properties of β-cyclodextrin and the effects of processing variables on inclusion complex formation, compactibility and dissolution

The tableting properties of a number of commercially available β-cyclodextrins were characterized. Fluidity was insufficient for routine direct compression. Compactibility varied by source but was excellent. Lubrication requirements were minimal. An inclusion complex of β-cyclodextrin/Progesterone was formed and the tableting properties of the complex were compared to those of a physical mixture in both directly compressed and wet granulated products. Inclusion complexes spontaneously formed during wet granulation processing. Substantial differences in tableting properties were found as processing variables were changed. β-cyclodextrin exhibits considerable promise as a standard filler binder in tableting.     

“Low-Tech” Innovations

This paper is about an industrial sector which, according to the usual socio-scientific indicators, is referred to as “low-tech”, respectively as non-research intensive and which mostly comprises “traditional” industries. The interest in this sector is motivated by the contradictory situation that, on the one hand, the debate about the perspectives of modern societies focuses on the rapidly growing importance of technological innovations, knowledge and research-intensive economic sectors while, on the other hand, traditional industries make up a considerable fraction of employment and production, especially also in developed economies. On the basis of the results of extensive empirical research, this contribution tries to find answers to the basic question, whether one can speak of an innovation mode typical of the low-tech sector. The institutional based innovation systems approach forms the categorical basis of the analysis. In order to elucidate the specific features of low-tech innovations, they are, in conclusion, compared to the general characteristics of high-tech-based innovation processes.     

Internal friction behaviour of Ni–Mn–Ga

The internal friction (IF) behaviour of shape memory alloys (SMA) is characterised by an IF peak and a minimum of the elastic modulus during the martensitic transformation (MT), and a higher IF value in the martensitic state than in parent phase. The IF peak is considered to be built of three contributions, the most important of them being the so-called “transient” one, existing only at non-zero temperature rate. On the other hand, the ferromagnetic Ni–Mn–Ga system alloys undergoes a MT from the L2₁ ordered parent phase to martensite, the characteristics of the transformation depending largely on the e/a ratio of the alloys. Indeed, a variety of transformation sequences, including intermediate phases between parent and martensite and intermartensitic transformations, have been observed for a wide set of studied alloys. Furthermore, the IF and modulus behaviour during cooling and heating these alloys show specific characteristics, such as modulus anomalies, strong temperature dependence of the elastic modulus, temperature dependent internal friction in martensite, and, as a general trend, a low transient contribution to the IF. In the present work, the IF and modulus behaviour of several Ni–Mn–Ga alloys will be reviewed and compared to that observed for “classical” systems like Cu- or NiTi-based shape memory alloys.     

Fatigue life enhancement of aluminium joints through mechanical and thermal prestressing

This paper presents some simple and flexible methods to enhance the fatigue life of welded aluminium components. Besides enhancing the fatigue life, the proposed methods can easily be implemented into manufacturing processes. The key element of the methods is to change residual stresses from tension to compression at locations vulnerable to fatigue. This is accomplished by mechanical prestressing using elastic pre-deformation or by thermal prestressing using induction heating. The specimens tested are welded aluminium rectangular hollow section T-joints. Prior to fatigue testing, welding FE-simulations were carried out to verify the magnitude and pattern of the residual stress fields (through process modeling). Fatigue testing was later carried out on four different batches. One batch was produced using elastically pre-deformed chords, two batches were treated by means of thermal prestressing (induction heating), and one batch was “as welded” representing a “reference case”. Based on statistical evaluation of S–N data, the introduction of superimposed compressive stress fields results in a significantly improved fatigue life. Among the different batches, induction heating turned out to be the most promising method with a fatigue strength improvement factor of 1.5 on stress, compared to “as welded” components.     

On the combined influences of Young''s modulus and stress ratio on the LEFM fatigue crack growth process: A new mechanistic approach

A new mechanistic approach (NMA) was used recently to examine the physical aspects of LEFM (long) fatigue crack growth (FCG) process in crack-ductile materials in stages I and II. In this paper, NMA is extended to examine both the physical and analytical aspects of the combined effects of Young's modulus, E and stress ratio, R, in the same stages of the same materials. It is shown that, (i) with submicroscopic cleavage or reversed shear mechanism operating in the pure form, E is the most influential intrinsic “material” property controlling FCG, (ii) E-dependence of da/dN is a natural consequence of near-crack-tip displacement control proposed previously, and (iii) the demonstrated similarity of FCG curves and the existence of characteristic “pivot points” on these curves for a “class of materials” results from E-influence which continues even at a higher R. A simple analytical model based on “strain intensity factor,” K₀, which contains E-influence implicitly and controls da/dN in all materials irrespective of class, is proposed. Model-predicted K₀-based theoretical values of threshold, “Idealised Master Growth Curves (IMGCs)” and mechanism transition point, all agreed excellently with experimental data for at least three classes of materials, i.e. steels, Al-alloys and Ti-alloys at extreme R-values of 0 and ≥ 0.6. The K₀-parameter concept is used here to raise the status of the analysis of the E-effect from a simple “normalisation” to that of direct data “representation”. Using NMA existing empirical relations are given some sound theoretical base. In addition to aiding in a clearer physical understanding of the FCG process, the unique IMGCs developed for different R-values are considered useful in quick, accurate and conservative life estimations, and performing failure analyses usually required in selection and design of materials.     

Deposition and etch processes: continuum film evolution in microelectronics

Aspects of modeling and simulation of topography evolution during deposition and etch processes used in the fabrication of integrated circuits are discussed. Overall, we hope to demonstrate that combined simulation and experimental studies of film profiles and composition profiles inside features is a valuable tool in efforts to arrive at useful kinetic and transport models. In particular, conformality limitations and film composition variations inside features for films deposited at low pressures are explained using examples of studies that combine transport and reaction simulations of deposition processes and carefully designed experimental work. The technical presentation is divided into three major parts. In the first section, we demonstrate that thermal systems can be modeled without “calibrating” the transport and reaction models used, though calibration can still be useful. The process considered in this section is the thermal deposition of SiO₂ from TEOS (tetraethoxysilane). We discuss the use of film profile information to decide between two kinetic models for the deposition process, then we discuss one way to integrate reactor scale and feature scale models in order to capture “microloading” due to changes in local pattern density. The second section demonstrates the state of topography simulation for plasma processes. We demonstrate the use of physically motivated models that in general require calibration from experimental data for a given set of operating conditions. As our first plasma example, we use the sputter deposition of Ti–W to demonstrate the existence of composition profiles inside features. We then use etch simulations to show how simulations can be used to test proposed chemical and/or physical phenomena. The last major section is a case study on plasma enhanced deposition of SiO₂ from TEOS and oxygen (PETEOS) that demonstrates the roles of “3d/2d” and “3d/3d” (transport dimensionality/surface dimensionality) topography simulators in “virtual wafer fabs”. The same methodology would apply to most topography relevant processes, including thin film flow processes.     

Exploring the effects of chemical composition in hot rolled steel product using Mahalanobis distance scale under Mahalanobis–Taguchi system

Classification of hot rolled steel product from the point of view of reaching the target mechanical property, based on chemical composition of the steel, is a common objective practiced in the industrial rolling mill. After examining the ability of measurement scale of Mahalanobis–Taguchi system in classifying the steel plate as “OK” or “Diverted”, study on the changing nature of Mahalanobis distance, obtained from previous work, with the corresponding increments in the chemical composition over their respective working ranges, is carried out in order to explain the behaviour of Mahalanobis distances from the knowledge of materials science. As the nature of Mahalanobis distance illustrated by the study does not contradict the subject knowledge, the robustness of the measurement scale used in Mahalanobis–Taguchi system is therefore established.     

An improved model for the prediction of intra-cell buckling in CFRP sandwich panels under in-plane compressive loading

Local instability in the form of “intra-cell buckling” or “dimpling” is a well-known failure mode in honeycomb-cored sandwich panels with very thin faces. Most work reported on the subject suggests relatively simple design formulae for the estimation of the intra-cell buckling load. It is however widely known that these classical design formulae in some cases considerably underpredict the intra-cell buckling load. In this paper a series of experimental results obtained for different CFRP/honeycomb sandwich panel configurations loaded in compression are presented. The results confirm that the “classical” design formulae provide overly conservative results. During the tests the intra-cell buckling patterns were monitored carefully, and it was observed that the hitherto assumed buckling patterns did not correspond to the experimental observations. Based on these findings a new simplified design formula is suggested, which for the investigated CFRP/honeycomb sandwich panels provides significantly more accurate predictions than the “classical” design formulae.     

Simulation of semi-solid thixoforging using a micro-macro constitutive equation

The constitutive equation of the isothermal steady-state behaviour of semi-solid materials is described with a micro-macro modelling. It is based on the application of the micromechanics concept of “coated inclusion” to semi-solid behaviour and the introduction of an evolving bimodal distribution of the liquid and solid phases. The micro-macro modelling is implemented in the FE code Forge2. The influence of the normal and abnormal namely softening stress–strain rate relationship on thixoforging is analyzed using compression and extrusion tests simulations.     

Improvement of Heater Surface Flatness and Uniformity of TiN Film Deposition

The deposition rate and the thickness uniformity of chemical vapor deposition (CVD) titanium nitride films depend on wafer temperatures. The heater surface conditions, such as flatness, roughness, and surface imperfections, can greatly affect heat transfer efficiency from the heater surface to the wafer, and the process performance. Because heater surface imperfections or “hot spots” that caused poor uniformity had to be eliminated, the origin of “hot spots” was identified by a detailed study of heater surface profiles. A better visualization of “hot spots” could be obtained by comparing wafer-chucking patterns with deposition patterns. Thus, the time needed to locate “hot spots” could be shortened. The manufacturing process was revised to prevent “hot spots” and improve heater performance.