The influence of formulation and manufacturing process parameters on the characteristics of lyophilized orally disintegrating tablets

Gelatin is a principal excipient used as a binder in the formulation of lyophilized orally disintegrating tablets. The current study focuses on exploiting the physicochemical properties of gelatin by varying formulation parameters to determine their influence on orally disintegrating tablet (ODT) characteristics. Process parameters, namely pH and ionic strength of the formulations, and ball milling were investigated to observe their effects on excipient characteristics and tablet formation. The properties and characteristics of the formulations and tablets which were investigated included: glass transition temperature, wettability, porosity, mechanical properties, disintegration time, morphology of the internal structure of the freeze-dried tablets, and drug dissolution. The results from the pH study revealed that adjusting the pH of the formulation away from the isoelectric point of gelatin, resulted in an improvement in tablet disintegration time possibly due to increase in gelatin swelling resulting in greater tablet porosity. The results from the ionic strength study revealed that the inclusion of sodium chloride influenced tablet porosity, tablet morphology and the glass transition temperature of the formulations. Data from the milling study showed that milling the excipients influenced formulation characteristics, namely wettability and powder porosity. The study concludes that alterations of simple parameters such as pH and salt concentration have a significant influence on formulation of ODT. © 2011 by the authors; licensee MDPI, Basel, Switzerland.

Implementation of chirped fibre Bragg gratings (CFBG) as optical wear sensors

This study discusses the fabrication and implementation of chirped fiber Bragg grating (CFBG) as optical wear sensors. Such a sensor has potential applications in monitoring grinding and milling machines through a safety device to check the wear on a car brake. The CFBG wear sensor has advantages over existing wear sensing techniques as it does not require electrical current to be passed through the sensor itself. This makes it eligible for application in combustible environments such as in the oil and gas industry.

A holistic multi evidence approach to study the fragmentation behaviour of crystalline mannitol

Mannitol is an essential excipient employed in orally disintegrating tablets due to its high palatability. However its fundamental disadvantage is its fragmentation during direct compression, producing mechanically weak tablets. The primary aim of this study was to assess the fracture behaviour of crystalline mannitol in relation to the energy input during direct compression, utilising ball milling as the method of energy input, whilst assessing tablet characteristics of post-milled powders. Results indicated that crystalline mannitol fractured at the hydrophilic (011) plane, as observed through SEM, alongside a reduction in dispersive surface energy. Disintegration times of post-milled tablets were reduced due to the exposure of the hydrophilic plane, whilst more robust tablets were produced. This was shown through higher tablet hardness and increased plastic deformation profiles of the post-milled powders, as observed with a lower yield pressure through an out-of-die Heckel analysis. Evaluation of crystal state using x-ray diffraction/differential scanning calorimetry showed that mannitol predominantly retained the β-polymorph; however x-ray diffraction provided a novel method to calculate energy input into the powders during ball milling. It can be concluded that particle size reduction is a pragmatic strategy to overcome the current limitation of mannitol fragmentation and provide improvements in tablet properties.

Methodology to create cost estimation models for engineer-to-order operations

This research addresses the problem of cost estimation for product development in engineer-to-order (ETO) operations. An ETO operation starts the product development process with a product specification and ends with delivery of a rather complicated, highly customized product. ETO operations are practiced in various industries such as engineering tooling, factory plants, industrial boilers, pressure vessels, shipbuilding, bridges and buildings. ETO views each product as a delivery item in an industrial project and needs to make an accurate estimation of its development cost at the bidding and/or planning stage before any design or manufacturing activity starts. ^ Many ETO practitioners rely on an ad hoc approach to cost estimation, with use of past projects as reference, adapting them to the new requirements. This process is often carried out on a case-by-case basis and in a non-procedural fashion, thus limiting its applicability to other industry domains and transferability to other estimators. In addition to being time consuming, this approach usually does not lead to an accurate cost estimate, which varies from 30% to 50%. ^ This research proposes a generic cost modeling methodology for application in ETO operations across various industry domains. Using the proposed methodology, a cost estimator will be able to develop a cost estimation model for use in a chosen ETO industry in a more expeditious, systematic and accurate manner. ^ The development of the proposed methodology was carried out by following the meta-methodology as outlined by Thomann. Deploying the methodology, cost estimation models were created in two industry domains (building construction and the steel milling equipment manufacturing). The models are then applied to real cases; the cost estimates are significantly more accurate than the actual estimates, with mean absolute error rate of 17.3%. ^ This research fills an important need of quick and accurate cost estimation across various ETO industries. It differs from existing approaches to the problem in that a methodology is developed for use to quickly customize a cost estimation model for a chosen application domain. In addition to more accurate estimation, the major contributions are in its transferability to other users and applicability to different ETO operations. ^

High pressure and low temperature study of ammonia borane and lithium amidoborane

Hydrogen has been considered as a potentially efficient and environmentally friendly alternative energy solution. However, one of the most important scientific and technical challenges that the "hydrogen economy" faces is the development of safe and economically viable on-board hydrogen storage for fuel cell applications, especially to the transportation sector. Ammonia borane (BH3NH 3), a solid state hydrogen storage material, possesses exceptionally high hydrogen content (19.6 wt%).However, a fairly high temperature is required to release all the hydrogen atoms, along with the emission of toxic borazine. Recently research interests are focusing on the improvement of H2 discharge from ammonia borane (AB) including lowering the dehydrogenation temperature and enhancing hydrogen release rate using different techniques. Till now the detailed information about the bonding characteristics of AB is not sufficient to understand details about its phases and structures. ^ Elemental substitution of ammonia borane produces metal amidoboranes. Introduction of metal atoms to the ammonia borane structure may alter the bonding characteristics. Lithium amidoborane is synthesized by ball milling of ammonia borane and lithium hydride. High pressure study of molecular crystal provides unique insight into the intermolecular bonding forces and phase stability. During this dissertation, Raman spectroscopic study of lithium amidoborane has been carried out at high pressure in a diamond anvil cell. It has been identified that there is no dihydrogen bond in the lithium amidoborane structure, whereas dihydrogen bond is the characteristic bond of the parent compound ammonia borane. It has also been identified that the B-H bond becomes weaker, whereas B-N and N-H bonds become stronger than those in the parent compound ammonia borane. At high pressure up to 15 GPa, Raman spectroscopic study indicates two phase transformations of lithium amidoborane, whereas synchrotron X-ray diffraction data indicates only one phase transformation of this material. ^ Pressure and temperature has a significant effect on the structural stability of ammonia borane. This dissertation explored the phase transformation behavior of ammonia borane at high pressure and low temperature using in situ Raman spectroscopy. The P-T phase boundary between the tetragonal (I4mm) and orthorhombic (Pmn21) phases of ammonia borane has been determined. The transition has a positive Clapeyron slope which indicates the transition is of exothermic in nature. Influence of nanoconfinemment on the I4mm to Pmn2 1 phase transition of ammonia borane was also investigated. Mesoporus silica scaffolds SBA-15 with pore size of ~8 nm and MCM-41 with pore size of 2.1-2.7 nm, were used to nanoconfine ammonia borane. During cooling down, the I4mm to Pmn21 phase transition was not observed in MCM-41 nanoconfined ammonia borane, whereas the SBA-15 nanocondfined ammonia borane shows the phase transition at ~195 K. Four new phases of ammonia borane were also identified at high pressure up to 15 GPa and low temperature down to 90 K.^

Synthesis of copper carbon nanotube composite and its electrical conductivity measurement

The matrices in which Multi Walled Carbon Nanotubes (MWCNTs) are incorporated to produce composites with improved electrical properties can be polymer, metal or metal oxide. Most composites containing CNTs are polymer based because of its flexibility in fabrication. Very few investigations have been focused on CNT-metal composites due to fabrication difficulties, such as achievement of homogeneous distribution of MWCNTs and poor interfacial bonding between MWCNTs and the metal matrix. In an effort to overcome poor interfacial bonding for the Cu - MWCNT composite, silver (Ag) and nickel (Ni) resinates have been incorporated in the ball milling stage. Composites of MWCNT (16, 12, and 8 Vol %) - Cu+Ag+Ni were pelleted at 20,000 psi (669.4 Mpa) and sintered at 950 °C. The electrical conductivity results measured by four probe meter showed that the conductivity decreases with increase in the porosity. Moreover from these results it can also be stated that an addition of optimum value of (12 Vol %) MWCNT leads to high electrical conductivity (9.26E+07 s-m"), which is 50% greater than the conductivity of Cu. It is anticipated that the conductivity can be increased substantially with hot isostatic pressing of the pellet.

Síntese e caracterização estrutural, magnética e térmica da hidroxiapatita dopada com ferro

In this work, composites were prepared using high energy mechanical milling from the precursors hydroxyapatite - HAp (Ca10(PO4)6(OH)2) and metallic iron ( -Fe ). The main goal here is to study composites in order to employ them in magnetic hyperthermia for cancer therapy. The produced samples were characterized by X-ray di raction (XRD), scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), magnetization curves as a function of applied eld (MxH), and nally measurements of magnetic hyperthermia. The XRD patterns of the milled samples HAp/Fe revealed only the presence of precursor materials. The SEM showed clusters with irregular shapes. The magnetization curves indicated typical cases of weak ferromagnetic behavior. For samples submitted to grinding and annealing, the identi ed phases were: HAp (Ca10(PO4)6(OH)2), hematite (Fe2O3) and Calcium Iron Phosphate (Ca9Fe(PO4)7). Analyzing the results of MxH, there was a reduction of the saturation magnetization, given that the Fe was incorporated into HAp. Hysteresis curves obtained at 300 K are characteristics of samples possessing over a phase. At 77 K, the behavior of the hysteresis curve is in uenced by the presence of hematite, which is antiferromagnetic. Already at T = 4.2 K, it is observed a weak ferromagnetic behavior. Furthermore, there is the e ect of exchange bias. Regarding the magnetic hyperthermia, the results of temperature measurements as a function of the alternating eld are promising for applications in magnetic hyperthermia and other biomedical applications.

Densificação e microestrutura de um compósito Mo-Cu preparado a partir de um pó de heptamolibidato de amônia e cobre

The Cu-Mo system is a composite used in the electrical industry as material for electrical contact and resistance welding electrode as well as the heat sink and microwave absorber in microelectronic devices. The use of this material in such applications is due to the excellent properties of thermal and electrical conductivity and the possibility of adjustment of its coefficient of thermal expansion to meet those of materials used as substrates in the semiconductor micoreletrônic industry. Powder metallurgy through the processes of milling, pressing shaping and sintering is a viable technique for consolidation of such material. However, the mutual insolubility of both phases and the low wettability of liquid Cu on Mo impede its densification. However, the mutual insolubility of both phases and the low wettability of liquid Cu on Mo impede its densification. The mechanical alloying is a technique for preparation of powders used to produce nanocrystalline composite powder with amorphous phase or extended solid solution, which increases the sinterability immiscible systems such as the Mo-Cu. This paper investigates the influence of ammonium heptamolybdate (HMA) and the mechanical alloying in the preparation of a composite powder HMA-20% Cu and the effect of this preparation on densification and structure of MoCu composite produced. HMA and Cu powders in the proportion of 20% by weight of Cu were prepared by the techniques of mechanical mixing and mechanical alloying in a planetary mill. These were milled for 50 hours. To observe the evolution of the characteristics of the particles, powder samples were taken after 2, 10, 15, 20, 30 and 40 hours of milling. Cylindrical samples 5 to 8 mm in diameter and 3 to 4 mm thickness were obtained by pressing at 200 MPa to the mixed powders so as to ground. These samples were sintered at 1200 ° C for 60 minutes under an atmosphere of H2. To determine the effect of heating rate on the structure of the material during the decomposition and reduction of HMA, rates of 2, 5 and 10 ° C / min were used .. The post and the structures of the sintered samples were characterized by SEM and EDS. The density of the green and sintered bodies was measured using the geometric method (weight / volume). Vickers microhardness with a load of 1 N for 15 s were performed on sintered structures. The density of the sintered structures 10 ° C / min. reached 99% of theoretical density, how the density of sintered structures to 2 ° C / min. reached only 90% of the theoretical density

Estudo de um compósito Nb-15%pCu obtidos por moagem de alta energia e sinterizados por fase líquida

There is great difficulty in forming a composite refractory metal niobium with copper. This is due to the fact that Nb-Cu system is almost mutually immiscible and may be neglected solubility between them. These properties hinder or prevent obtaining homogeneous and high-density structures, conventionally prepared. This study aims to analyze the use of high-energy milling process (MAE) to implement these natural difficulties, with regard to the densification of the sintered bodies. The MAE and the press were used in the preparation of powders, to obtain a fine and homogeneous distribution of the grain size. Four loads Nb and Cu powders containing 15% by weight of Cu were then milled for MAE in a planetary type ball mill under various milling times and speeds. The results obtained by MAE were analyzed by scanning electron microscopy (SEM), according to the parameters of time and grinding speed. The samples were compacted under pressure of 200 MPa, were then sintered in liquid phase in a vacuum furnace at temperatures of 1100 ° C / 60 min and 1200 ° C / 60 min. Then it was used to characterize diffraction of X-rays to identify the phases. The microstructures of the sintered samples were observed and evaluated using scanning electron microscopy (SEM). Vickers Microhardness tests were performed, obtaining higher values for the sintered bodies in the largest of the post milling times and the larger grinding speeds. It was found that the liquid phase sintering of the samples that were processed by MAE produced at the end of a homogeneous and densified structure in 77,4% relative to the value of the theoretical density of the composite

Efeito da moagem de alta energia na densificação e microestrutura do compósito AI2O3-Cu

The Cu-Al2O3 composite ceramic combines the phase of alumina, which is extremely hard and durable, yet very brittle, to metallic copper phase high ductility and high fracture toughness. These characteristics make this material a strong candidate for use as a cutting tool. Al2O3-Cu composite powders nanocrystalline and high homogeneity can be produced by high energy milling, as well as dense and better mechanical structures can be obtained by liquid phase sintering. This work investigates the effect of high-energy milling the dispersion phase Al2O3, Cu, and the influence of the content of Cu in the formation of Cu-Al2O3 composite particles. A planetary mill Pulverisatte 7 high energy was used to perform the experiments grinding. Al2O3 powder and Cu in the proportion of 5, 10 and 15% by weight of Cu were placed in a container for grinding with balls of hard metal and ethyl alcohol. A mass ratio of balls to powder of 1:5 was used. All powders were milled to 100 hours, and powder samples were collected after 2, 10, 20, 50 and 70 hours of grinding. Composite powders with compact cylindrical shape of 8 mm diameter were pressed and sintered in uniaxial matrix resistive furnace to 1200, 1300 to 1350 °C for 60 minutes under an atmosphere of argon and hydrogen. The heating rate used was 10°C/min. The powders and structures of the sintered bodies were characterized by XRD, SEM and EDS. Analysis TG, DSC and particle size were also used to characterize the milled powders, as well as dilatometry was used to observe the contraction of the sintered bodies. The density of the green and sintered bodies was measured using the geometric method (mass / volume). Vickers microhardness with a load of 500 g for 10 s were performed on sintered structures. The Cu-Al2O3 composite with 5% copper density reached 61% of theoretical density and a hardness of 129 HV when sintered at 1300 ° C for 1h. In contrast, lower densities (59 and 51% of the theoretical density) and hardness (110 HV and 105) were achieved when the copper content increases to 10 and 15%.

Estudo de duas pseudoligas de Nb-Cu obtidas pela rota da metalurgia do pó

The Nb-Cu pseudoalloys present themselves as potential substitutes for the alloys from a well known system and already commercially applied, as the W-Cu alloys, used in applications such as heat sinks, electrical contacts and coils for the generation of high magnetic fields. Because it is an immiscible system, where there is mutual insolubility and low wettability of the liquid Cu on the Nb surface, the processing route used in this work was the Powder Metallurgy. Two Nb alloys were used, with additions of 10% and 20% in weight of Cu, and times of 20, 30 and 40 hours for the high energy milling of the starting powders. The milling evolution of the powders is presented through the characterization techniques, such as the LASER diffraction for particle size, XRD, SEM, EDS, DSC, dilatometry, TEM and chemical analysis. After the milling, portions of the loads were submitted to the annealing heat treatment. The process used for the samples consolidation was the hot pressing, which has been applied both on some milled powders samples, as on the annealed powders. Subsequent heat treatments were performed in the samples at temperatures of 1000ºC (solid phase) and 1100ºC (in the Cu liquid phase). All sets of consolidated samples, and also the two sets of the heat treated, were analyzed by XRD, SEM, EDS, density and Vickers microhardness. Moreover, other Nb powder samples with 10% and 20% in weight of Cu obtained by simple mechanical mixing, were consolidated, thermally treated and characterized with the same techniques applied to the others, and the results were compared among themselves. Despite the difficulty of consolidation and densification of the two pseudoalloys of the Nb-Cu system of this study, on the route that passes through the HEM, samples were obtained with densities around 90% of the theoretical density. And, on the processing route of which were only mixed, the values reached up to 97%. Therefore, in this work are also emphasized the processes that made possible these results.

Estudo da influência da adição de níquel em alumina pela rota da metalurgia do pó

Ceramic materials alumina basis have been widely used in structural components, mainly because owning properties such as high hardness, chemical inertness and good wear resistance, however, the low toughness is a factor that compromises its use in many other applications, featuring the addition of nickel as a possible solution to this problem, in this context, this work aims to study the addition of nickel alumina using the route of powder metallurgy processing of the material. The percentage of nickel were added 2, 4 and 6 wt%; and each composition to high energy milling in a planetary mill was performed for 2, 4, 9 and 16h. Subsequently, the samples were compacted at 300 MPa and sintered in a vacuum oven at 1400⁰C for 2h. The samples were characterized as the physical and mechanical properties, observing, in general, an improvement in sinterability of the material with increasing grinding time and nickel content, and mixing with a decrease of porosity and increase of hardness, density values above 80% of theoretical were obtained. The milling time of 4 hours and addition of 2% nickel, particularly if achieved higher hardness (HV 1068.7 +/- 32.6) and density of about 99% theoretical density.

Estudo da influência da adição de níquel em alumina pela rota da metalurgia do pó

Ceramic materials alumina basis have been widely used in structural components, mainly because owning properties such as high hardness, chemical inertness and good wear resistance, however, the low toughness is a factor that compromises its use in many other applications, featuring the addition of nickel as a possible solution to this problem, in this context, this work aims to study the addition of nickel alumina using the route of powder metallurgy processing of the material. The percentage of nickel were added 2, 4 and 6 wt%; and each composition to high energy milling in a planetary mill was performed for 2, 4, 9 and 16h. Subsequently, the samples were compacted at 300 MPa and sintered in a vacuum oven at 1400⁰C for 2h. The samples were characterized as the physical and mechanical properties, observing, in general, an improvement in sinterability of the material with increasing grinding time and nickel content, and mixing with a decrease of porosity and increase of hardness, density values above 80% of theoretical were obtained. The milling time of 4 hours and addition of 2% nickel, particularly if achieved higher hardness (HV 1068.7 +/- 32.6) and density of about 99% theoretical density.

Efeito da adição de WC e Co na sinterização e propriedades mecânicas da alumina

Composites based on alumina (Al2O3), tungsten carbide (WC) and cobalt (Co) exhibit specific properties such as low density, high oxidation resistance, high melting point and high chemical inertia. That composite shows to be a promising material for application in various fields of engineering. In this work, the mechanical properties of the composite (Al2O3 – WC – Co), particularly density and hardness, were evaluated according to the effects of the variables of powder processing parameters, green compact and sintered. Powder composites with the composition of 80 wt% Al2O3, 18 wt% WC and 2 wt% Co were processed by high energy ball milling in a planetary mill for 50 hours as well as mixed by manual mixing in a glass vessel with the same proportion. Samples were collected (2, 10, 20, 30, 40 and 50 hours) during the milling process. Then, the powders were compacted in a cylindrical die with 5 mm in diameter in a uniaxial press with pressures of 200 and 400 MPa. The sintering was in two stages: first, the solid phase sintering was performed at 1126 and 1300 °C for 1 hour with a heating rate of 10 °C/min in a resistive furnace under argon atmosphere for green samples compacted in 200 and 400 MPa; the second sintering was performed on dilatometer in solid phase at 1300 °C for green sample compacted in 200 MPa, another sintering also was performed on dilatometer, this time in liquid phase at 1550 °C for green samples compacted in 200 and 400 MPa, with the same parameters used in resistive furnace. The raw materials were characterized by X – ray diffraction (XRD), X – ray fluorescence (XRF), scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS) and laser particlemeter. The sintered samples were subjected to microhardness testing. The results showed that high energy milling achieved to the objectives regarding the particle size and the dispersion of composite phases. However, the hardness did not achieve to significant results, this is an indication that the composite has low fracture toughness.

Efeito da adição de WC e Co na sinterização e propriedades mecânicas da alumina

Composites based on alumina (Al2O3), tungsten carbide (WC) and cobalt (Co) exhibit specific properties such as low density, high oxidation resistance, high melting point and high chemical inertia. That composite shows to be a promising material for application in various fields of engineering. In this work, the mechanical properties of the composite (Al2O3 – WC – Co), particularly density and hardness, were evaluated according to the effects of the variables of powder processing parameters, green compact and sintered. Powder composites with the composition of 80 wt% Al2O3, 18 wt% WC and 2 wt% Co were processed by high energy ball milling in a planetary mill for 50 hours as well as mixed by manual mixing in a glass vessel with the same proportion. Samples were collected (2, 10, 20, 30, 40 and 50 hours) during the milling process. Then, the powders were compacted in a cylindrical die with 5 mm in diameter in a uniaxial press with pressures of 200 and 400 MPa. The sintering was in two stages: first, the solid phase sintering was performed at 1126 and 1300 °C for 1 hour with a heating rate of 10 °C/min in a resistive furnace under argon atmosphere for green samples compacted in 200 and 400 MPa; the second sintering was performed on dilatometer in solid phase at 1300 °C for green sample compacted in 200 MPa, another sintering also was performed on dilatometer, this time in liquid phase at 1550 °C for green samples compacted in 200 and 400 MPa, with the same parameters used in resistive furnace. The raw materials were characterized by X – ray diffraction (XRD), X – ray fluorescence (XRF), scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS) and laser particlemeter. The sintered samples were subjected to microhardness testing. The results showed that high energy milling achieved to the objectives regarding the particle size and the dispersion of composite phases. However, the hardness did not achieve to significant results, this is an indication that the composite has low fracture toughness.