A comparison of Lorentz gauge formulations in eddy currentcomputations

The modified vector potential provides a computationally acceptable formulation for many problems but leads to difficulties when one has to cope with (a) interconductor interfaces and (b) problems where the frequency conductivity product is low. The authors investigate the use of the Lorentz gauge as a curative to the difficulties encountered by the modified magnetic vector potential formulation. The uniqueness conditions are examined, and three different implementations of the Lorentz gauge are compared and contrasted. A classically motivated Lorentz gauge formulation is shown theoretically to produce unique solutions and in practice to produce results comparable to those given by other researchers. The limitations of the modified vector potential formulation have been overcome with the minimum of overhead     

Formulation and in vitro evaluation of self-emulsifying formulations of Cinnarizine

The main objectives of this study were to improve the aqueous solubility and to modify in vitro dissolution profile of hydrophobic drug using self-emulsifying drug delivery systems (SEDDS). SEDDS were formulated using Capmul PG-12, Cremophor RH 40 and Tween 20 at different weight ratios and incorporated with Cinnarizine. The drug incorporation into pre-concentrate and drug solubility in phosphate buffer (pH 7.2) were investigated. In addition, the mean droplet size and drug release profile of the SEDDS were also determined. The drug incorporation was over 120?mg per 0.5?g pre-concentrate regardless of the composition of the formulations. The solubility of Cinnarizine in phosphate buffer (pH 7.2) was at least 1500 μM in the SEDDS. Formulations with only 10% w/w Capmul PG-12 were less than 20?nm in mean diameter while those produced with at least 20% w/w Capmul PG-12 were more than 100?nm regardless of the ratios of Cremophor RH 40 to Tween 20. SEDDS showed a significant increase of the mean percentage drug release than pure drug (p?相似文献   

Formulation and in vitro evaluation of self-emulsifying formulations of Cinnarizine

The main objectives of this study were to improve the aqueous solubility and to modify in vitro dissolution profile of hydrophobic drug using self-emulsifying drug delivery systems (SEDDS). SEDDS were formulated using Capmul PG-12, Cremophor RH 40 and Tween 20 at different weight ratios and incorporated with Cinnarizine. The drug incorporation into pre-concentrate and drug solubility in phosphate buffer (pH 7.2) were investigated. In addition, the mean droplet size and drug release profile of the SEDDS were also determined. The drug incorporation was over 120?mg per 0.5?g pre-concentrate regardless of the composition of the formulations. The solubility of Cinnarizine in phosphate buffer (pH 7.2) was at least 1500 μM in the SEDDS. Formulations with only 10% w/w Capmul PG-12 were less than 20?nm in mean diameter while those produced with at least 20% w/w Capmul PG-12 were more than 100?nm regardless of the ratios of Cremophor RH 40 to Tween 20. SEDDS showed a significant increase of the mean percentage drug release than pure drug (p?<?0.0001). In general, the SEDDS with 30% w/w of Capmul PG-12 provided the greatest enhancement in drug solubility in phosphate buffer as well as rapid drug release despite forming larger droplets upon emulsification. The combination of Capmul PG-12, Tween 20 and Cremophor RH 40 can produce SEDDS which can be used as an alternative dosage form for poorly water soluble drug.     

Drug release kinetics from tablet matrices based upon ethylcellulose ether-derivatives: a comparison between different formulations

The present study involved the preparation of ibuprofen-containing controlled release tablets formulated from either the established granular product, Ethocel®Standard Premium, or the novel finely-milled product, Ethocel®Standard FP Premium. The tablets were prepared by either direct compression or wet granulation. The aim was to explore the influence of different parameters on the kinetics and mechanisms of ibuprofen release from the tablets. These parameters were; polymer particle size, polymer molecular weight, drug : polymer ratio, preparation methodology and partial replacement of lactose with the coexcipient—hydroxypropyl methylcellulose (HPMC). The derived drug release data were analyzed with reference to various established mathematical models while the f₂-metric technique was used in order to determine profile equivalency. It was found that drug release was mostly modulated by several interactive factors apparently exhibiting crosstalk. Nevertheless, it was possible to identify some simple rules. Incorporation of Ethocel® FP polymers and application of the wet granulation technique facilitated greater efficiency in controlling ibuprofen release behavior from the matrices. Furthermore, drug release profiles could be modulated by partial substitution of the primary excipient with HPMC. Polymer concentrations and particle sizes, rather than viscosity grade, were found to be decisive factors in controlling drug release rates.     

Chitosan formulations for steroid delivery: effect of formulation variables on in vitro characteristics

Chitosan film formulations for steroid delivery after craniomaxillofacial surgery were formulated by using three different types of chitosan with respect to their molecular weight as low, medium and high. Film formulations were prepared by casting/solvent evaporation technique. In vitro characterization, film thickness, equilibrium swelling degree, in vitro release profiles and surface morphologies were investigated. For two different types of crosslinkings, the release of dexamethasone sodium phosphate (DSP) can be extended as the molecular weight increases. As a result, chitosan film formulations should be beneficial for steroid delivery for a certain time after craniomaxillofacial surgery.     

Chance-constrained formulations in rolling horizon production planning: an experimental study

Rolling horizon procedures, where an infinite horizon problem is approximated by the solution to a sequence of finite horizon problems, are common in production planning practice and research. However, these procedures also lead to frequent changes in planned release and production quantities, a phenomenon referred to as nervousness. We examine the performance of two chance-constrained production planning models developed for systems with stochastic demand in a rolling horizon environment, and find that these formulations significantly reduce planned release changes (nervousness) while also improving cost and service-level performance.     

Ophthalmic delivery of ciprofloxacin hydrochloride from different polymer formulations: in vitro and in vivo studies

Reservoir-type ocular inserts were fabricated using sodium alginate containing ciprofloxacin hydrochloride as the core (drug reservoir) that was sandwiched between the Eudragit and/or polyvinylacetate films. Ocular inserts were packaged in aluminium foil and sterilized by gamma radiation. These were tested for sterility as per British Pharmacopoeia (BP). Ocular inserts were evaluated for in vitro release rate studies, microbial efficacy, in vivo release studies, efficacy against induced bacterial conjunctivitis in rabbit's eyes, concentration in the aqueous humor, and stability studies as per the International Conference on Harmonization (ICH) guidelines. Ocular inserts passed the test for sterility. They showed zero-order release of the drug in the in vitro and in vivo release studies over a period of 120 hr. The drug was found to be active against selected microorganisms as was proved by microbial efficacy studies. A high correlation coefficient was found between in vitro and in vivo release rate studies. Better improvement was observed in artificially induced bacterial conjunctivitis in rabbit's eyes, compared with marketed eye drops and placebo. Drug concentration in the aqueous humor was found above Minimum Inhibitory Concentration (MIC-90) against selected microorganisms. Shelf-life of the product was found to be more than 2 years.     

Relating in vitro/in vivo data of two controlled-release metformin formulations

This study was conducted to compare the bioavailability of two controlled-release metformin preparations (Diabetmin Retard and Glucophage Retard) and also to correlate the in vitro and in vivo data obtained with the two preparations. Twelve healthy volunteers participated in the study, conducted according to a completely randomized, two-way crossover design. The preparations were compared using area under the plasma concentration-time curve AUC0-infinity, time to reach peak plasma concentration Tmax, and peak plasma concentration Cmax, while correlation was determined between in vitro release and in vivo absorption. Diabetmin Retard demonstrated a slower rate of in vitro release, but a faster rate of in vivo absorption than Glucophage Retard. However, the in vivo absorption of both products was found to be slower than that of drug released in vitro. A satisfactory relationship could be established between the in vitro and in vivo results, but there was no rank order correlation. No statistically significant difference was observed between the two preparations in the parameters AUC0-infinity and Cmax. However, a slight but statistically significant difference was observed between the Tmax values, but it may not be therapeutically significant. Moreover, the 90% confidence interval for the ratio of the logarithmic transformed AUC0-infinity values, as well as the logarithmic transformed Cmax values, of Diabetmin Retard over those of Glucophage Retard was within the acceptance criteria of 0.80-1.25.     

Assessment of drug release from oil depot formulations using an in vitro model -- potential applicability in accelerated release testing

In vitro drug release and transport rates from oil depot formulations under nonsink conditions have been investigated in the rotating dialysis cell model. Eight model drug compounds and eight oil vehicle compositions were used for the releaseexperiments. The experimentally obtained apparent first-order rate constants related to the drug appearance in the acceptor phase after initial instillation of a drug-containing oil solution were found to be in excellent agreement with the rate constants obtained from a theoretically derived expression. It was observed that the drug oil-water distribution coefficient was the key parameter influencing the release characteristics. As compared with ketoprofen, flurbiprofen exhibited a higher affinity for the oil, resulting in a significantly lower and more slowly decreasing drug concentrations in the aqueous donor compartment. Release profiles for prilocaine and the more lipophilic agent bupivacaine after incorporation of both drugs in fractionated coconut oil were characterized by a fast release of prilocaine, whereas bupivacaine was liberated much slower to the acceptor phase. The high oil-buffer interfacial area generated in vitro by rotation of the donor cell tends to overestimate release rates in comparison to those expected in vivo, for example, after intra-articular administration of oil solutions. The present in vitro method may constitute a valuable tool in accelerated in vitro release testing of parenteral oil depot formulations in areas comprising formulation design and product quality control.     

Infinite elements for wave problems: a review of current formulations and an assessment of accuracy

Infinite element schemes for unbounded wave problems are reviewed and a procedure is presented forassessing their performance. A general computational scheme is implemented in which orthogonal functions are used for the transverse interpolation within the infinite element region. This is used as a basis for numerical studies of the effectiveness of various combinations of the radial test and trial functions which give rise to different conjugated and unconjugated formulations. Results are presented for the test case of a spherical radiator to which infinite elements are directly attached. Accuracy of the various schemes is assessed for pure multipole solutions of arbitrary order. Previous studies which have indicated that the conjugated and unconjugated schemes are more effective in the far and near fields, respectively, are confirmed by the current results. All of the schemes tested converge to the exact solution as radial order increases. All are however susceptible to ill conditioning. This places practical restrictions on their effectiveness at high radial orders. A close relationship is demonstrated between the discrete equations which arise from first‐order infiniteelement schemes and those derived from the application of more traditional, local non‐reflecting boundary conditions. Copyright © 2000 John Wiley & Sons, Ltd.     

In vitro release studies of flurbiprofen from different topical formulations

The release profiles of flurbiprofen (F) from different gel and ointment formulations were studied in order to evaluate factors governing the release process. Carbopol 934P (CAB), poloxamer 407 (POL), and eudragit S100 (EUD) gel bases were used, while emulsion (EML) and polyethylene glycol (PEG) ointments were employed. The release studies were conducted using membraneless diffusion cells and lipophilic receptor medium, isopropyl myristate (IPM). The effects of gelling agent concentrations and the initial drug load on drug release were determined. Hydrogels were observed to give higher amounts of drug release than hydrophobic EUD gel and ointments, despite the lower bulk viscosity of these bases. Flurbiprofen release from CAB gels was 3.06-1.56-fold higher than from other formulations. Over a 4-hr period, the amount of F released was 492.8 and 316.0 µg/cm² from 2% CAB and 25% POL gels, while it was 213.05, 168.61, and 160.9 µg/cm² from EML, 40% EUD, and PEG bases, respectively. The diffusivity of F in the gel bases was an inverse function of the polymer concentrations over the range of 1-3% CAB, 20-30% POL, and 35-45% EUD gels. Drug release was increased from the bases as the initial F concentration increased over the range 0.25-1.0%, while the diffusion coefficient observed an inverse relationship. The CAB and POL gels could be the vehicles of choice for the rapid release and onset of F after topical application.     

Simultaneous estradiol and levonorgestrel transdermal delivery from a 7-day patch: in vitro and in vivo drug deliveries of three formulations

A new drug-in-adhesive transdermal patch was developed to deliver both estradiol and levonorgestrel through the skin over a 7-day period, but at different rates. This report elucidates the in vitro and in vivo biopharmaceutical studies that were necessary during the development of this product. Three test patches had to be manufactured, all delivering estradiol at the same rate, but delivering levonorgestrel at three different rates so that a levonorgestrel dose response could be studied in the clinic. An in vitro hairless mouse skin model (HMS) using modified Franz diffusion cells was used to select the test products delivering levonorgestrel in the order of 1:2:3. HMS experiments also demonstrated that the presence of estradiol did not affect the flux of levonorgestrel. Two in vivo studies in postmenopausal women showed that at steady state (four weeks of once-weekly dosing) the three test products all delivered estradiol at comparable rates. Similarly, the levonorgestrel deliveries for the three test products were in the order expected. The target fluxes of both drugs were achieved in these three test products by varying the drug loads and patch size. That this approach was successful is evidence of the value of using the HMS penetration experiments in transdermal product development and should provide useful insights for other formulations having to develop complex systems. One of the test products is now marketed as Climara Pro^TM.     

Studies of floating dosage forms of furosemide: in vitro and in vivo evaluations of bilayer tablet formulations

For the purpose of enhancement the bioavailability of furosemide (FR), a floating dosage form with controlled release of FR was designed in this study. Because of the lower solubility of active material in the gastric medium, it was first enhanced by preparing an inclusion complex of FR with beta-cyclodextrin (beta-CD) in a 1:1 proportion using the kneading method. Following the design of dosage form, bilayer floating tablets were prepared. After dissolution rate studies were performed using the continuous flow-through cell method, the formulation that provided delivery of active material near the target profile was given to six healthy male volunteer subjects, and in vivo tests were performed. It was determined by radiographs that floating tablets prepared by adding BaSO4 stayed in the stomach for 6 hr. Further, values of the area under the plasma concentration-time curve (AUC) obtained with the floating dosage form were about 1.8 times those of the conventional FR tablet in blood analyses; maximum and minimum plasma concentrations were also found to be between the desired limits. In urine analyses, the peak diuretic effect seen in classical preparations was decreased and prolonged in floating dosage forms. Also, a considerably significant correlation was detected between in vivo results and in vitro data of the dissolution rate, and it was concluded that the modified continuous flow-through cell method is usable for in vitro dissolution rate tests of floating dosage forms.     

A comparison of discrete granular material models with continuous microplane formulations

The main objective of this paper is the discussion of two different strategies of simulating the constitutive behavior of granular assemblies. For this, we will focus on discrete particle methods which are widely used in physical science and on continuum–based microplane models which are applied by the engineering community. After deriving the overall constitutive equations based on Voigt’s hypothesis, special focus will be dedicated to the comparison of the relations between the microscopic and macroscopic quantities of each model. It will be demonstrated, that the two basically different modelling techniques lead to remarkably similar results for elastic as well as elasto–plastic material behavior. Received: 19 May 1999     

Nitinol surface roughness modulates in vitro cell response: a comparison between fibroblasts and osteoblasts

The purpose of the present in vitro study was to examine the biocompatibility of a nickel–titanium (NiTi) shape memory alloy. Human gingival fibroblastic and rat embryo osteoblastic cells were cultured on NiTi discs. The discs were prepared with two surface roughnesses. Cell response to these surfaces was compared for the two types of cells. The comparison was based on an analysis of the cell morphology, adhesion and proliferation rates. Fibronectin labeling by immunofluorescence staining was also performed. For osteoblastic cells, alkaline phosphatase assay was conducted as a function of NiTi surface roughness and for different durations.     

A comparison of mixed integer programming formulations of the capacitated lot-sizing problem

We propose a novel mixed integer programming formulation for the capacitated lot-sizing problem with set-up times and set-up carryover. We compare our formulation to two earlier formulations, the Classical and Modified formulations, and a more recent formulation due to Suerie and Stadtler. Extensive computational experiments show that our formulation consistently outperforms the Classical and Modified formulations in terms of CPU time and solution quality. It is competitive with the Suerie–Stadtler (S&S) formulation, but outperforms all other formulations on the most challenging instances, those with low-capacity slack and a dense jobs matrix. We show that some of the differences in the performance of these various formulations arise from their different use of binary variables to represent production or set-up states. We also show that the LP relaxation of our Novel formulation provides a tighter lower bound than that of the Modified formulation. Our experiments demonstrate that, while the S&S formulation provides a much tighter LP bound, the Novel formulation is better able to exploit the intelligence of the CPLEX solution engine.     

Becoming an Engineer: Toward a Three Dimensional View of Engineering Learning

In this paper we develop an analytical framework we refer to as “Becoming an Engineer” that focuses upon changes occurring over time as students traverse their undergraduate educations in engineering. This analytical framework involves three related dimensions that we track over time: disciplinary knowledge, identification, and navigation. Our analysis illustrates how these three dimensions enable us to understand how students become, or do not become, engineers by examining how these three interrelated dimensions unfold over time. This study is based on longitudinal ethnographic data from which we have developed “person‐centered ethnographies” focused on individual students' pathways through engineering. We present comparative analysis, spanning four schools and four years. We also present person‐centered ethnographic case studies that illustrate how our conceptual dimensions interrelate. Our discussion draws some educational implications from our analysis and proposes further lines of research.     

A comparison of piecewise linear programming formulations for stochastic disassembly line balancing

Recently, several mathematical programming formulations and solution approaches have been developed for the stochastic disassembly line balancing problem (DLBP). This paper aims at finding optimal solutions for the stochastic DLBP. Two second-order cone programming (SOCP1 and SOCP2) models and five piecewise linear mixed integer programming (PwLP) models are presented. The PwLP formulations involve two specially ordered sets of type 2 (S1 and S2) models and three convex combination (CC1, CC2 and CC3) models. In each modelling category, the latter models strengthen the initial S1 and CC1 models. Our computational analysis of a total 240 instances of ten problems demonstrates that all the seven models can be used to solve practical-sized DLBP problems to optimality using GUROBI. The SOCP2 model and the strengthened S2 and CC2 models lead to lower computation times, compared to SOCP1, S1, CC1 and CC3, respectively. Using the strengthened S2 and CC2 formulations, the CPU times of the CC3 model available in the literature can be reduced by 50 and 40%, respectively. Besides analysing the optimal solutions and the differences of the computation times, we present insights gained from our results.