Jan Van Humbeeck

Non-medical applications of shape memory alloys

Abstract The diversity of (potential) applications using shape memory alloys (SMA), apart from the medical field, becomes quite large. Classic categories such as free recovery, actuators, constrained recovery, pseudo-elasticity or damping require further specifications. For example, micro-actuators, smart materials or active damping, can be all classified as actuator applications, but each of those items demands specific functional performance, dimensions and processing. Furthermore, success for applications can only be realised in so far those materials offer also a price-competitive advantage relative to other functional materials or mechanical designs. This competition requires perfect control of the material performance. It is known that especially Ni–Ti alloys can be tuned relatively easy to some specific requirements of the envisaged application: hysteresis, transformation temperatures, damping capacity. At the other side little is known on recovery stresses, wear resistance, fracture mechanics, fatigue … In this paper we would like to stress the need for further exploration of the 4P-relation: principles–properties–processing–products as well in companies as in universities or other research laboratories. This will be illustrated by describing some actual applications indicating why they are successful, other applications why they failed and still others that can only be realised if some further, probably possible, material improvement can be realised.

Increasing the oral bioavailability of the poorly water soluble drug itraconazole with ordered mesoporous silica.

This study aims to evaluate the in vivo performance of ordered mesoporous silica (OMS) as a carrier for poorly water soluble drugs. Itraconazole was selected as model compound. Physicochemical characterization was carried out by SEM, TEM, nitrogen adsorption, DSC, TGA and in vitro dissolution. After loading itraconazole into OMS, its oral bioavailability was compared with the crystalline drug and the marketed product Sporanox in rabbits and dogs. Plasma concentrations of itraconazole and OH-itraconazole were determined by HPLC-UV. After administration of crystalline itraconazole in dogs (20mg), no systemic itraconazole could be detected. Using OMS as a carrier, the AUC0-8 was boosted to 681+/-566 nM h. In rabbits, the AUC0-24 increased significantly from 521+/-159 nM h after oral administration of crystalline itraconazole (8 mg) to 1069+/-278 nM h when this dose was loaded into OMS. Tmax decreased from 9.8+/-1.8 to 4.2+/-1.8h. No significant differences (AUC, Cmax, and Tmax) could be determined when comparing OMS with Sporanox in both species. The oral bioavailability of itraconazole formulated with OMS as a carrier compares well with the marketed product Sporanox, in rabbits as well as in dogs. OMS can therefore be considered as a promising carrier to achieve enhanced oral bioavailability for drugs with extremely low water solubility.

Ordered mesoporous silica material SBA-15: a broad-spectrum formulation platform for poorly soluble drugs.

Encapsulating poorly soluble drugs in mesoporous silicates is an emerging strategy to improve drug dissolution. This study evaluates the applicability of the ordered mesoporous silicate SBA-15 as an excipient to enhance dissolution, for a test series of 10 poorly soluble compounds with a high degree of physicochemical diversity (carbamazepine, cinnarizine, danazol, diazepam, fenofibrate, griseofulvin, indomethacin, ketoconazole, nifedipine, and phenylbutazone). A generic solvent impregnation method was used to load all model compounds. The target drug content was 20%. The physical nature of the formulations was investigated using differential scanning calorimetry (DSC) and the pharmaceutical performance evaluated by means of in vitro dissolution. Aliquots of each formulation were stored at 25 degrees C/52% RH for 6 months, and again subjected to DSC and in vitro dissolution. The target drug content of 20% was attained in all cases. DSC data evidenced the noncrystalline state of the confined drugs. All SBA-15 formulations exhibited an enhanced dissolution as compared to their corresponding crystalline materials, and the high pharmaceutical performance of all formulations was retained during the 6 months storage period. The results of this study suggest that encapsulation in SBA-15 can be applied as a dissolution-enhancing formulation approach for a very wide variety of poorly soluble drugs.

Physical state of poorly water soluble therapeutic molecules loaded into SBA-15 ordered mesoporous silica carriers: A case study with itraconazole and ibuprofen

The ordered mesoporous silica material SBA-15 was loaded with the model drugs itraconazole and ibuprofen using three different procedures: (i) adsorption from solution, (ii) incipient wetness impregnation, and (iii) heating of a mixture of drug and SBA-15 powder. The location of the drug molecules in the SBA-15 particles and molecular interactions were investigated using nitrogen adsorption, TGA, DSC, DRS UV-vis, and XPS. The in vitro release of hydrophobic model drugs was evaluated in an aqueous environment simulating gastric fluid. The effectiveness of the loading method was found to be strongly compound dependent. Incipient wetness impregnation using a concentrated itraconazole solution in dichloromethane followed by solvent evaporation was most efficient for dispersing itraconazole in SBA-15. The itraconazole molecules were located on the mesopore walls and inside micropores of the mesopore walls. When SBA-15 was loaded by slurrying it in a diluted itraconazole solution from which the solvent was evaporated, the itraconazole molecules ended up in the mesopores that they plugged locally. At a loading of 30 wt %, itraconazole exhibited intermolecular interactions inside the mesopores revealed by UV spectroscopy and endothermic events traced with DSC. The physical mixing of itraconazole and SBA-15 powder followed by heating above the itraconazole melting temperature resulted in formulations in which glassy itraconazole particles were deposited externally on the SBA-15 particles. Loading with ibuprofen was successful with each of the three loading procedures. Ibuprofen preferably is positioned inside the micropores. In vitro release experiments showed fast release kinetics provided the drug molecules were evenly deposited over the mesoporous surface.

A screening study of surface stabilization during the production of drug nanocrystals

In order to establish a knowledge base for nanosuspension production, a screening was performed on 13 different stabilizers at 3 concentrations for 9 structurally different drug compounds. Concerning the stabilizers tested, the group of semi-synthetic polymers was the least performant (stable nanosuspensions were obtained in only 1 out of 10 cases). For the linear synthetic polymers, better results were obtained with povidones, however poly(vinyl alcohol) did not result in adequate stabilization. The synthetic copolymers showed even higher success rates, resulting in nanosuspensions in two out of three cases when applied at a 100 wt% concentration (relative to the drug weight). Finally, the surfactants gave the best results, with TPGS being successful at concentrations of 25 or 100 wt% of the drug weight for all compounds tested. From the point of view of drug compound, large differences could be observed upon evaluation of the relative number of formulations of that compound resulting in nanosuspensions. It was found that the hydrophobicity of the surfaces, as estimated by the adsorbed amount of TPGS per unit of surface area of nanosuspensions stabilized with 25 wt% TPGS, was decisive for the agglomeration tendency of the particles and hence the ease of nanosuspensions stabilization.

Drying of crystalline drug nanosuspensions-the importance of surface hydrophobicity on dissolution behavior upon redispersion.

d-alpha-Tocopherol polyethylene glycol 1000 succinate (TPGS)-stabilized nanosuspensions (25wt%, relative to the drug weight) were produced by media milling for 9 model drug compounds [cinnarizine, griseofulvin, indomethacin, itraconazole, loviride, mebendazole, naproxen, phenylbutazone and phenytoin]. After 3 months of storage at room temperature, Ostwald ripening occurred in all of the samples, except for indomethacin. Whereas lowering the temperature could slow down the ripening, it markedly increased upon storage at 40 degrees C. As for ripening, settling generally became more pronounced at 40 degrees C compared to 4 degrees C. As the nanosuspensions were afflicted by Ostwald ripening and settling, we explored nanosuspension drying as a strategy to circumvent these stability issues. Spray-drying and freeze-drying were evaluated for nanosuspensions and coarse reference suspensions of the compounds. Nanoparticle agglomeration could be visually observed in all of the powders. To evaluate the effect of agglomeration on the key characteristic of drug nanocrystals (i.e. rapid dissolution), dissolution experiments were performed under poor sink conditions. It was found that the compounds could be categorized into 3 groups: (i) compounds for which it was impossible to differentiate between coarse and nanosized products (griseofulvin, mebendazole, naproxen), (ii) compounds that gave clear differences in dissolution profiles between the nanosized and the coarse products, but for which drying of the nanosuspensions did not decrease the dissolution performance of the product (indomethacin, loviride, phenytoin) and (iii) compounds that showed differences between coarse and nanosized products, but for which drying of the nanosuspensions resulted in a significant decrease of the dissolution rate (cinnarizine, itraconazole, phenylbutazone). To gain insight on the influence of the drug compound characteristics on the dissolution of the dried products, the dissolution behavior of the compounds of the second and the third group was linked to the compounds characteristics. It was found that compounds with a more hydrophobic surface resulted in agglomerates which were harder to disintegrate, for which dissolution was compromised upon drying. The same was found for compounds having higher logP values.

Enhanced absorption of the poorly soluble drug fenofibrate by tuning its release rate from ordered mesoporous silica

The aim of the present study was to evaluate the effect of release rate from ordered mesoporous silica materials on the rate and extent of absorption of the poorly soluble drug fenofibrate. Three ordered mesoporous silica materials with different pore diameter (7.3 nm, 4.4 nm and 2.7 nm) were synthesized and loaded with fenofibrate via impregnation. Release experiments were conducted under sink conditions and under supersaturating conditions in biorelevant media, simulating the fasted and the fed state. Subsequently, all silica-based formulations were evaluated in vivo (rat model). The release experiments under sink conditions indicated a clear increase in release rate with increasing pore size. However, under supersaturating conditions (FaSSIF), the, pharmaceutical performance (in terms of both the degree and duration of supersaturation), increased with decreasing pore size. The same trend was observed in vivo (fasted state): the area under the plasma concentration-time profile amounted to 102 ± 34 μMh, 86 ± 19 μMh and 20 ± 13 μMh for the materials with pore diameter of 2.7 nm, 4.4 nm and 7.3 nm, respectively. The results of this, study demonstrate that a decrease in drug release rate - and thus, a decrease of the rate at which supersaturation is created - is beneficial to the absorption of fenofibrate.

Some aspects of the properties of NiTi shape memory alloy

Abstract The damping capacity, tensile behaviour and the transformation characteristics of a NiTi shape memory alloy rolled sheet as a function of annealing conditions have been studied. Results show that both the martensite phase damping capacity and the stress for martensite phase reorientation are a function of annealing temperature. Attention has also been paid to the correlation between the damping capacity of the shape memory alloy and its other properties. Experimental results show that a higher damping of the martensite phase generally corresponds to a lower reorientation stress in the stress-strain curve, suggesting that the martensite phase damping capacity and the stress for martensite phase reorientation are interrelated. This result may provide the possibility of predicting one shape memory property from others in the same alloy.

Comparison of the effects of silicon and aluminium on the tensile behaviour of multiphase TRIP-assisted steels

Ghent University,Laboratory for Iron and Steelmaking, Technologiepark 9, B-9052 Ghent, Belgium(Received July 12, 2000)(Accepted in revised form November 21, 2000)Keywords: TRIP-steels; Microstructure; Phase transformations; Mechanical propertiesIntroductionMultiphase TRIP-assisted steels are a new generation of low alloy high strength steels that exhibitexceptional formability [1]. The remarkable strength to ductility balance results from the occurrenceduring testing of the Transformation Induced Plasticity (TRIP) phenomenon [2], which involves thestrain-induced transformation of austenite to martensite. The presence of austenite in the initialmicrostructure appears to be critical to the achievement of the desired properties. The retention ofaustenite is usually obtained by the combined effect of an appropriate chemistry and a typicalheat-treatment. In this respect, it is known that silicon and aluminium may both retard the kinetics ofcarbide formation and thus favour the austenite stabilisation by a bainitic holding stage [3]. Despite thisqualitative knowledge, very little literature can be found that rigorously compares the effect of siliconand aluminium on the austenite retention, on the extent of the TRIP effect, and on the resulting tensilebehaviour, all other chemical constituents have been kept constant [4]. The objective of this paper is toquantitatively assess the influence of aluminium and silicon contents, in view of the development ofmultiphase TRIP-assisted steels.Materials and Experimental ProcedureThe chemical compositions of the steels studied in this work are given in Table 1. Specific care wastaken to keep the same carbon content for each alloy. The slabs were initially hot and cold-rolled tothicknesses between 0.8mm and 1.0mm, following classical processing routes.The desired multiphase microstructure was obtained as displayed in Figure 1. The cold-rolledmaterial was first annealed for 4 minutes in the (a1g) region at a temperature 25°C above its Ac1temperature. It was then rapidly cooled and held at an intermediate temperature (i.e. between 375°C and450°C), where bainite formation takes place and contributes to the stabilisation of the austenite. Theheat-treatment was eventually interrupted by quenching the samples to room temperature. After the

Theoretical and experimental investigation on the solid solubility and miscibility of naproxen in poly(vinylpyrrolidone).

The objective of the present study was to determine the solid state solubility and miscibility of naproxen in poly(vinylpyrrolidone) (PVP) and the mutual interaction using the standard thermodynamic models and thermal analysis. Solid dispersions were prepared by spray drying several compositions of naproxen and PVP with different molecular weights, viz., PVP K 12, PVP K 25 and PVP K 90, and analyzed using modulated differential scanning calorimetry (mDSC). The kinetic miscibility limit in terms of a single mixed phase glass transition temperature was found to be relatively similar for the dispersions containing PVP with different chain lengths (>or=50% w/w drug in PVP). But the systems with different PVP followed diverse patterns of composition dependent mixed phase glass transition temperature as well as the degree of plasticization by water. The crystalline solid solubility values of naproxen in PVP estimated by using its solubility data in n-methylpyrrolidone, a low molecular weight analogue of PVP, were 6.42, 5.85 and 5.81% w/w of drug in PVP K 12, PVP K 25 and PVP K 90 respectively. The values estimated for corresponding amorphous solubility showed no marked difference. The remarkable difference between thermodynamic solubility/miscibility and kinetic miscibility implied that naproxen was highly supersaturated in the PVP solid dispersions and only stabilized kinetically. The negative value of the drug-polymer interaction parameter (-0.36) signified the systems to be favorably mixing. The melting point depression data of naproxen in PVP pointed to the composition dependence and chain length effect on the interaction. The moisture sorption by the physical mixtures not only provided the composition dependent interaction parameter but also conferred an estimate of composition dependent miscibility of naproxen in PVP in the presence of water.