An uncertainty analysis of the flood-stage upstream from a bridge.

PubMed

Sowiński, M

2006-01-01

The paper begins with the formulation of the problem in the form of a general performance function. Next the Latin hypercube sampling (LHS) technique--a modified version of the Monte Carlo method is briefly described. The essential uncertainty analysis of the flood-stage upstream from a bridge starts with a description of the hydraulic model. This model concept is based on the HEC-RAS model developed for subcritical flow under a bridge without piers in which the energy equation is applied. The next section contains the characteristic of the basic variables including a specification of their statistics (means and variances). Next the problem of correlated variables is discussed and assumptions concerning correlation among basic variables are formulated. The analysis of results is based on LHS ranking lists obtained from the computer package UNCSAM. Results fot two examples are given: one for independent and the other for correlated variables.

A robust approach to chance constrained optimal power flow with renewable generation

DOE PAGES

Lubin, Miles; Dvorkin, Yury; Backhaus, Scott N.

2016-09-01

Optimal Power Flow (OPF) dispatches controllable generation at minimum cost subject to operational constraints on generation and transmission assets. The uncertainty and variability of intermittent renewable generation is challenging current deterministic OPF approaches. Recent formulations of OPF use chance constraints to limit the risk from renewable generation uncertainty, however, these new approaches typically assume the probability distributions which characterize the uncertainty and variability are known exactly. We formulate a robust chance constrained (RCC) OPF that accounts for uncertainty in the parameters of these probability distributions by allowing them to be within an uncertainty set. The RCC OPF is solved usingmore » a cutting-plane algorithm that scales to large power systems. We demonstrate the RRC OPF on a modified model of the Bonneville Power Administration network, which includes 2209 buses and 176 controllable generators. In conclusion, deterministic, chance constrained (CC), and RCC OPF formulations are compared using several metrics including cost of generation, area control error, ramping of controllable generators, and occurrence of transmission line overloads as well as the respective computational performance.« less

Precision diet formulation to improve performance and profitability across various climates: Modeling the implications of increasing the formulation frequency of dairy cattle diets.

PubMed

White, Robin R; Capper, Judith L

2014-03-01

The objective of this study was to use a precision nutrition model to simulate the relationship between diet formulation frequency and dairy cattle performance across various climates. Agricultural Modeling and Training Systems (AMTS) CattlePro diet-balancing software (Cornell Research Foundation, Ithaca, NY) was used to compare 3 diet formulation frequencies (weekly, monthly, or seasonal) and 3 levels of climate variability (hot, cold, or variable). Predicted daily milk yield (MY), metabolizable energy (ME) balance, and dry matter intake (DMI) were recorded for each frequency-variability combination. Economic analysis was conducted to calculate the predicted revenue over feed and labor costs. Diet formulation frequency affected ME balance and MY but did not affect DMI. Climate variability affected ME balance and DMI but not MY. The interaction between climate variability and formulation frequency did not affect ME balance, MY, or DMI. Formulating diets more frequently increased MY, DMI, and ME balance. Economic analysis showed that formulating diets weekly rather than seasonally could improve returns over variable costs by $25,000 per year for a moderate-sized (300-cow) operation. To achieve this increase in returns, an entire feeding system margin of error of <1% was required. Formulating monthly, rather than seasonally, may be a more feasible alternative as this requires a margin of error of only 2.5% for the entire feeding system. Feeding systems with a low margin of error must be developed to better take advantage of the benefits of precision nutrition. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

On the convergence of an iterative formulation of the electromagnetic scattering from an infinite grating of thin wires

NASA Technical Reports Server (NTRS)

Brand, J. C.

1985-01-01

Contraction theory is applied to an iterative formulation of electromagnetic scattering from periodic structures and a computational method for insuring convergence is developed. A short history of spectral (or k-space) formulation is presented with an emphasis on application to periodic surfaces. The mathematical background for formulating an iterative equation is covered using straightforward single variable examples including an extension to vector spaces. To insure a convergent solution of the iterative equation, a process called the contraction corrector method is developed. Convergence properties of previously presented iterative solutions to one-dimensional problems are examined utilizing contraction theory and the general conditions for achieving a convergent solution are explored. The contraction corrector method is then applied to several scattering problems including an infinite grating of thin wires with the solution data compared to previous works.

A New Formulation for Fresh Snow Density over Antarctica for the regional climate model Modèle Atmosphérique Régionale (MAR).

NASA Astrophysics Data System (ADS)

Tedesco, M.; Datta, R.; Fettweis, X.; Agosta, C.

2015-12-01

Surface-layer snow density is important to processes contributing to surface mass balance, but is highly variable over Antarctica due to a wide range of near-surface climate conditions over the continent. Formulations for fresh snow density have typically either used fixed values or been modeled empirically using field data that is limited to specific seasons or regions. There is also currently limited work exploring how the sensitivity to fresh snow density in regional climate models varies with resolution. Here, we present a new formulation compiled from (a) over 1600 distinct density profiles from multiple sources across Antarctica and (b) near-surface variables from the regional climate model Modèle Atmosphérique Régionale (MAR). Observed values represent coastal areas as well as the plateau, in both West and East Antarctica (although East Antarctica is dominant). However, no measurements are included from the Antarctic Peninsula, which is both highly topographically variable and extends to lower latitudes than the remainder of the continent. In order to assess the applicability of this fresh snow density formulation to the Antarctic Peninsula at high resolutions, a version of MAR is run for several years both at low-resolution at the continental scale and at a high resolution for the Antarctic Peninsula alone. This setup is run both with and without the new fresh density formulation to quantify the sensitivity of the energy balance and SMB components to fresh snow density. Outputs are compared with near-surface atmospheric variables available from AWS stations (provided by the University of Wisconsin Madison) as well as net accumulation values from the SAMBA database (provided from the Laboratoire de Glaciologie et Géophysique de l'Environnement).

Dynamic rupture modeling with laboratory-derived constitutive relations

USGS Publications Warehouse

Okubo, P.G.

1989-01-01

A laboratory-derived state variable friction constitutive relation is used in the numerical simulation of the dynamic growth of an in-plane or mode II shear crack. According to this formulation, originally presented by J.H. Dieterich, frictional resistance varies with the logarithm of the slip rate and with the logarithm of the frictional state variable as identified by A.L. Ruina. Under conditions of steady sliding, the state variable is proportional to (slip rate)-1. Following suddenly introduced increases in slip rate, the rate and state dependencies combine to produce behavior which resembles slip weakening. When rupture nucleation is artificially forced at fixed rupture velocity, rupture models calculated with the state variable friction in a uniformly distributed initial stress field closely resemble earlier rupture models calculated with a slip weakening fault constitutive relation. Model calculations suggest that dynamic rupture following a state variable friction relation is similar to that following a simpler fault slip weakening law. However, when modeling the full cycle of fault motions, rate-dependent frictional responses included in the state variable formulation are important at low slip rates associated with rupture nucleation. -from Author

[Optimization of Formulation and Process of Paclitaxel PEGylated Liposomes by Box-Behnken Response Surface Methodology].

PubMed

Shi, Ya-jun; Zhang, Xiao-feil; Guo, Qiu-ting

2015-12-01

To develop a procedure for preparing paclitaxel encapsulated PEGylated liposomes. The membrane hydration followed extraction method was used to prepare PEGylated liposomes. The process and formulation variables were optimized by "Box-Behnken Design (BBD)" of response surface methodology (RSM) with the amount of Soya phosphotidylcholine (SPC) and PEG2000-DSPE as well as the rate of SPC to drug as independent variables and entrapment efficiency as dependent variables for optimization of formulation variables while temperature, pressure and cycle times as independent variables and particle size and polydispersion index as dependent variables for process variables. The optimized liposomal formulation was characterized for particle size, Zeta potential, morphology and in vitro drug release. For entrapment efficiency, particle size, polydispersion index, Zeta potential, and in vitro drug release of PEGylated liposomes was found to be 80.3%, (97.15 ± 14.9) nm, 0.117 ± 0.019, (-30.3 ± 3.7) mV, and 37.4% in 24 h, respectively. The liposomes were found to be small, unilamellar and spherical with smooth surface as seen in transmission electron microscopy. The Box-Behnken response surface methodology facilitates the formulation and optimization of paclitaxel PEGylated liposomes.

Variable thickness transient ground-water flow model. Volume 1. Formulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reisenauer, A.E.

1979-12-01

Mathematical formulation for the variable thickness transient (VTT) model of an aquifer system is presented. The basic assumptions are described. Specific data requirements for the physical parameters are discussed. The boundary definitions and solution techniques of the numerical formulation of the system of equations are presented.

Recent experience in simultaneous control-structure optimization

NASA Technical Reports Server (NTRS)

Salama, M.; Ramaker, R.; Milman, M.

1989-01-01

To show the feasibility of simultaneous optimization as design procedure, low order problems were used in conjunction with simple control formulations. The numerical results indicate that simultaneous optimization is not only feasible, but also advantageous. Such advantages come at the expense of introducing complexities beyond those encountered in structure optimization alone, or control optimization alone. Examples include: larger design parameter space, optimization may combine continuous and combinatoric variables, and the combined objective function may be nonconvex. Future extensions to include large order problems, more complex objective functions and constraints, and more sophisticated control formulations will require further research to ensure that the additional complexities do not outweigh the advantages of simultaneous optimization. Some areas requiring more efficient tools than currently available include: multiobjective criteria and nonconvex optimization. Efficient techniques to deal with optimization over combinatoric and continuous variables, and with truncation issues for structure and control parameters of both the model space as well as the design space need to be developed.

Finite element techniques for the Navier-Stokes equations in the primitive variable formulation and the vorticity stream-function formulation

NASA Technical Reports Server (NTRS)

Glaisner, F.; Tezduyar, T. E.

1987-01-01

Finite element procedures for the Navier-Stokes equations in the primitive variable formulation and the vorticity stream-function formulation have been implemented. For both formulations, streamline-upwind/Petrov-Galerkin techniques are used for the discretization of the transport equations. The main problem associated with the vorticity stream-function formulation is the lack of boundary conditions for vorticity at solid surfaces. Here an implicit treatment of the vorticity at no-slip boundaries is incorporated in a predictor-multicorrector time integration scheme. For the primitive variable formulation, mixed finite-element approximations are used. A nine-node element and a four-node + bubble element have been implemented. The latter is shown to exhibit a checkerboard pressure mode and a numerical treatment for this spurious pressure mode is proposed. The two methods are compared from the points of view of simulating internal and external flows and the possibilities of extensions to three dimensions.

A Geographically Variable Water Quality Index Used in Oregon.

ERIC Educational Resources Information Center

Dunnette, D. A.

1979-01-01

Discusses the procedure developed in Oregon to formulate a valid water quality index which accounts for the specific conditions in the water body of interest. Parameters selected include oxygen depletion, BOD, eutrophication, dissolved substances, health hazards, and physical characteristics. (CS)

Spray-drying nanocapsules in presence of colloidal silica as drying auxiliary agent: formulation and process variables optimization using experimental designs.

PubMed

Tewa-Tagne, Patrice; Degobert, Ghania; Briançon, Stéphanie; Bordes, Claire; Gauvrit, Jean-Yves; Lanteri, Pierre; Fessi, Hatem

2007-04-01

Spray-drying process was used for the development of dried polymeric nanocapsules. The purpose of this research was to investigate the effects of formulation and process variables on the resulting powder characteristics in order to optimize them. Experimental designs were used in order to estimate the influence of formulation parameters (nanocapsules and silica concentrations) and process variables (inlet temperature, spray-flow air, feed flow rate and drying air flow rate) on spray-dried nanocapsules when using silica as drying auxiliary agent. The interactions among the formulation parameters and process variables were also studied. Responses analyzed for computing these effects and interactions were outlet temperature, moisture content, operation yield, particles size, and particulate density. Additional qualitative responses (particles morphology, powder behavior) were also considered. Nanocapsules and silica concentrations were the main factors influencing the yield, particulate density and particle size. In addition, they were concerned for the only significant interactions occurring among two different variables. None of the studied variables had major effect on the moisture content while the interaction between nanocapsules and silica in the feed was of first interest and determinant for both the qualitative and quantitative responses. The particles morphology depended on the feed formulation but was unaffected by the process conditions. This study demonstrated that drying nanocapsules using silica as auxiliary agent by spray drying process enables the obtaining of dried micronic particle size. The optimization of the process and the formulation variables resulted in a considerable improvement of product yield while minimizing the moisture content.

Applying SDDP to very large hydro-economic models with a simplified formulation for irrigation: the case of the Tigris-Euphrates river basin.

NASA Astrophysics Data System (ADS)

Rougé, Charles; Tilmant, Amaury

2015-04-01

Stochastic dual dynamic programming (SDDP) is an optimization algorithm well-suited for the study of large-scale water resources systems comprising reservoirs - and hydropower plants - as well as irrigation nodes. It generates intertemporal allocation policies that balance the present and future marginal value of water while taking into account hydrological uncertainty. It is scalable, in the sense that the time and memory required for computation do not grow exponentially with the number of state variables. Still, this scalability relies on the sampling of a few relevant trajectories for the system, and the approximation of the future value of water through cuts -i.e., hyperplanes - at points along these trajectories. Therefore, the accuracy of this approximation arguably decreases as the number of state variables increases, and it is important not to have more than necessary. In previous formulations, SDDP had three types of state variables, namely storage in each reservoir, inflow at each node and water accumulated during the irrigation season for each crop at each node. We present a simplified formulation for irrigation that does not require using the latter type of state variable. It also requires only two decision variables for each irrigation site, where the previous formulation had four per crop - and there may be several crops at the same site. This reduction in decision variables effectively reduces computation time, since SDDP decomposes the stochastic, multiperiodic, non-linear maximization problem into a series of linear ones. The proposed formulation, while computationally simpler, is mathematically equivalent to the previous one, and therefore the model gives the same results. A corollary of this formulation is that marginal utility of water at an irrigation site is effectively related to consumption at that site, through a piecewise linear function representing the net benefits from irrigation. Last but not least, the proposed formulation can be extended to any type of consumptive use of water beyond irrigation, e.g., municipal, industrial, etc This slightly different version of SDDP is applied to a large portion of the Tigris-Euphrates river basin. It comprises 24 state variables representing storage in reservoirs, 28 hydrologic state variables, and 51 demand nodes. It is the largest yet to simultaneously consider hydropower and irrigation within the same river system, and the proposed formulation almost halves the number of state variables to be considered.

Spinning fluids in general relativity. II - Self-consistent formulation

NASA Technical Reports Server (NTRS)

Ray, John R.; Smalley, Larry, L.; Krisch, Jean P.

1987-01-01

Methods used earlier to derive the equations of motion for a spinning fluid in the Einstein-Cartan theory are specialized to the case of general relativity. The main idea is to include the spin as a thermodynamic variable in the theory.

Application of variable-gain output feedback for high-alpha control

NASA Technical Reports Server (NTRS)

Ostroff, Aaron J.

1990-01-01

A variable-gain, optimal, discrete, output feedback design approach that is applied to a nonlinear flight regime is described. The flight regime covers a wide angle-of-attack range that includes stall and post stall. The paper includes brief descriptions of the variable-gain formulation, the discrete-control structure and flight equations used to apply the design approach, and the high performance airplane model used in the application. Both linear and nonlinear analysis are shown for a longitudinal four-model design case with angles of attack of 5, 15, 35, and 60 deg. Linear and nonlinear simulations are compared for a single-point longitudinal design at 60 deg angle of attack. Nonlinear simulations for the four-model, multi-mode, variable-gain design include a longitudinal pitch-up and pitch-down maneuver and high angle-of-attack regulation during a lateral maneuver.

Modeling vehicle operating speed on urban roads in Montreal: a panel mixed ordered probit fractional split model.

PubMed

Eluru, Naveen; Chakour, Vincent; Chamberlain, Morgan; Miranda-Moreno, Luis F

2013-10-01

Vehicle operating speed measured on roadways is a critical component for a host of analysis in the transportation field including transportation safety, traffic flow modeling, roadway geometric design, vehicle emissions modeling, and road user route decisions. The current research effort contributes to the literature on examining vehicle speed on urban roads methodologically and substantively. In terms of methodology, we formulate a new econometric model framework for examining speed profiles. The proposed model is an ordered response formulation of a fractional split model. The ordered nature of the speed variable allows us to propose an ordered variant of the fractional split model in the literature. The proposed formulation allows us to model the proportion of vehicles traveling in each speed interval for the entire segment of roadway. We extend the model to allow the influence of exogenous variables to vary across the population. Further, we develop a panel mixed version of the fractional split model to account for the influence of site-specific unobserved effects. The paper contributes substantively by estimating the proposed model using a unique dataset from Montreal consisting of weekly speed data (collected in hourly intervals) for about 50 local roads and 70 arterial roads. We estimate separate models for local roads and arterial roads. The model estimation exercise considers a whole host of variables including geometric design attributes, roadway attributes, traffic characteristics and environmental factors. The model results highlight the role of various street characteristics including number of lanes, presence of parking, presence of sidewalks, vertical grade, and bicycle route on vehicle speed proportions. The results also highlight the presence of site-specific unobserved effects influencing the speed distribution. The parameters from the modeling exercise are validated using a hold-out sample not considered for model estimation. The results indicate that the proposed panel mixed ordered probit fractional split model offers promise for modeling such proportional ordinal variables. Copyright © 2013 Elsevier Ltd. All rights reserved.

Optimizing the taste-masked formulation of acetaminophen using sodium caseinate and lecithin by experimental design.

PubMed

Hoang Thi, Thanh Huong; Lemdani, Mohamed; Flament, Marie-Pierre

2013-09-10

In a previous study of ours, the association of sodium caseinate and lecithin was demonstrated to be promising for masking the bitterness of acetaminophen via drug encapsulation. The encapsulating mechanisms were suggested to be based on the segregation of multicomponent droplets occurring during spray-drying. The spray-dried particles delayed the drug release within the mouth during the early time upon administration and hence masked the bitterness. Indeed, taste-masking is achieved if, within the frame of 1-2 min, drug substance is either not released or the released amount is below the human threshold for identifying its bad taste. The aim of this work was (i) to evaluate the effect of various processing and formulation parameters on the taste-masking efficiency and (ii) to determine the optimal formulation for optimal taste-masking effect. Four investigated input variables included inlet temperature (X1), spray flow (X2), sodium caseinate amount (X3) and lecithin amount (X4). The percentage of drug release amount during the first 2 min was considered as the response variable (Y). A 2(4)-full factorial design was applied and allowed screening for the most influential variables i.e. sodium caseinate amount and lecithin amount. Optimizing these two variables was therefore conducted by a simplex approach. The SEM and DSC results of spray-dried powder prepared under optimal conditions showed that drug seemed to be well encapsulated. The drug release during the first 2 min significantly decreased, 7-fold less than the unmasked drug particles. Therefore, the optimal formulation that performed the best taste-masking effect was successfully achieved. Copyright © 2013 Elsevier B.V. All rights reserved.

Evaluation of new chlorhexidine- and cetylpyridinium chloride-based mouthrinse formulations adjunctive to scaling and root planing: pilot study.

PubMed

García-Gargallo, M; Zurlohe, M; Montero, E; Alonso, B; Serrano, J; Sanz, M; Herrera, D

2017-11-01

To compare the effect of two newly formulated chlorhexidine (CHX) and cetylpyridinium chloride (CPC) mouthrinses after scaling and root planing (SRP) in terms of clinical, microbiological, patient-based variables and adverse events, with a positive control with the same active components, already marketed and tested. A pilot, randomized clinical trial, double-blind, parallel design with 1-month follow-up was conducted. Chronic periodontitis patients requiring non-surgical periodontal therapy were enrolled and randomly assigned to: (i) SRP and test-1 (new reformulation: 0.12% CHX and 0.05% CPC); (ii) SRP and test-2 (new formulation: 0.03% CHX and 0.05% CPC); or (iii) SRP and positive control (commercial product: 0.12% CHX and 0.05% CPC). All variables were evaluated at baseline and 1 month after SRP. Quantitative variables were compared by means of anova or Kruskal-Wallis test and qualitative variables by chi-square or McNemar tests. Thirty patients (10 per group) were included. After 1 month, there were significant differences among groups in plaque levels (P = 0.016) as test-1 showed less sites with plaque than test-2 (31.15% [standard error-SE 2.21%] versus 49.39% [SE 4.60%), respectively). No significant differences were found for global patient perception of the product or in adverse effects. Test groups showed better results in levels and proportions (P = 0.022) of Capnocytophaga spp. Within the limitations of this pilot study, it can be concluded that the newly formulated 0.12% CHX and 0.05% CPC mouthrinse showed larger plaque level reductions, without showing more adverse effects, when compared to the other two mouthrinses, after SRP. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Optimization of formulation variables of benzocaine liposomes using experimental design.

PubMed

Mura, Paola; Capasso, Gaetano; Maestrelli, Francesca; Furlanetto, Sandra

2008-01-01

This study aimed to optimize, by means of an experimental design multivariate strategy, a liposomal formulation for topical delivery of the local anaesthetic agent benzocaine. The formulation variables for the vesicle lipid phase uses potassium glycyrrhizinate (KG) as an alternative to cholesterol and the addition of a cationic (stearylamine) or anionic (dicethylphosphate) surfactant (qualitative factors); the percents of ethanol and the total volume of the hydration phase (quantitative factors) were the variables for the hydrophilic phase. The combined influence of these factors on the considered responses (encapsulation efficiency (EE%) and percent drug permeated at 180 min (P%)) was evaluated by means of a D-optimal design strategy. Graphic analysis of the effects indicated that maximization of the selected responses requested opposite levels of the considered factors: For example, KG and stearylamine were better for increasing EE%, and cholesterol and dicethylphosphate for increasing P%. In the second step, the Doehlert design, applied for the response-surface study of the quantitative factors, pointed out a negative interaction between percent ethanol and volume of the hydration phase and allowed prediction of the best formulation for maximizing drug permeation rate. Experimental P% data of the optimized formulation were inside the confidence interval (P < 0.05) calculated around the predicted value of the response. This proved the suitability of the proposed approach for optimizing the composition of liposomal formulations and predicting the effects of formulation variables on the considered experimental response. Moreover, the optimized formulation enabled a significant improvement (P < 0.05) of the drug anaesthetic effect with respect to the starting reference liposomal formulation, thus demonstrating its actually better therapeutic effectiveness.

Assessing bioequivalence of generic antiepilepsy drugs.

PubMed

Krauss, Gregory L; Caffo, Brian; Chang, Yi-Ting; Hendrix, Craig W; Chuang, Kelly

2011-08-01

Patients with epilepsy are often concerned that switching between brand-name and generic formulations of antiepilepsy drugs (AEDs) may cause clinically significant changes in plasma drug concentrations. We assessed bioequivalence (BE) studies for approved generic AEDs to evaluate US Food and Drug Administration claims that: (1) generic AEDs are accurate copies of reference formulations; (2) delivery of reference formulations may be as variable as generic AEDs and so provide no increased benefit; and (3) switches between generic AED formulations are safe and effective. We determined differences in 90% confidence interval limits for total drug exposure (AUC(0-t) ) and peak concentration (Cmax) ratios of generic and reference formulations during fasting and fed BE studies. We simulated BE between generic formulations after adjusting for reference values. AUC(0-t) values of approved reference and generic formulations differed by <15% in 99% of BE studies; Cmax differed by <15% in 89% of studies. Food affected variability of Cmax but not AUC(0-t) . Intersubject variability in Cmax and AUC(0-t) was small and similar for reference and generic products. In simulated switches between 595 pairs of generic AED formulations, estimated AUC(0-t) differed by >15% for 17% of pairs; estimated Cmax differed by >15% for 39%. AEDs with low bioavailability and solubility (eg, oxcarbazepine) had the greatest variability in BE. Most generic AED products provide total drug delivery (AUC) similar to reference products; differences in peak concentrations between formulations are more common. Switches between generic AED products may cause greater changes in plasma drug concentrations than generic substitutions of reference products. Copyright © 2011 American Neurological Association.

Inventory of oral anticancer agents: Pharmaceutical formulation aspects with focus on the solid dispersion technique.

PubMed

Sawicki, E; Schellens, J H M; Beijnen, J H; Nuijen, B

2016-11-01

Dissolution from the pharmaceutical formulation is a prerequisite for complete and consistent absorption of any orally administered drug, including anticancer agents (oncolytics). Poor dissolution of an oncolytic can result in low oral bioavailability, high variability in blood concentrations and with that suboptimal or even failing therapy. This review discusses pharmaceutical formulation aspects and absorption pharmacokinetics of currently licensed orally administered oncolytics. In nearly half of orally dosed oncolytics poor dissolution is likely to play a major role in low and unpredictable absorption. Dissolution-limited drug absorption can be improved with a solid dispersion which is a formulation method that induces super-saturated drug dissolution and with that it enhances in vivo absorption. This review discusses formulation principles with focus on the solid dispersion technology and how it works to enhance drug absorption. There are currently three licensed orally dosed oncolytics formulated as a solid dispersion (everolimus, vemurafenib and regorafenib) and these formulations result in remarkably improved dissolution and absorption compared to what can be achieved with conventional formulations of the respective oncolytics. Because of the successful implementation of these three solid dispersion formulations, we encourage the application of this formulation method for poorly soluble oral oncolytics. Copyright © 2016 Elsevier Ltd. All rights reserved.

Development and Evaluation of Topical Gabapentin Formulations

PubMed Central

Alcock, Natalie; Hiom, Sarah; Birchall, James C.

2017-01-01

Topical delivery of gabapentin is desirable to treat peripheral neuropathic pain conditions whilst avoiding systemic side effects. To date, reports of topical gabapentin delivery in vitro have been variable and dependent on the skin model employed, primarily involving rodent and porcine models. In this study a variety of topical gabapentin formulations were investigated, including Carbopol® hydrogels containing various permeation enhancers, and a range of proprietary bases including a compounded Lipoderm® formulation; furthermore microneedle facilitated delivery was used as a positive control. Critically, permeation of gabapentin across a human epidermal membrane in vitro was assessed using Franz-type diffusion cells. Subsequently this data was contextualised within the wider scope of the literature. Although reports of topical gabapentin delivery have been shown to vary, largely dependent upon the skin model used, this study demonstrated that 6% (w/w) gabapentin 0.75% (w/w) Carbopol® hydrogels containing 5% (w/w) DMSO or 70% (w/w) ethanol and a compounded 10% (w/w) gabapentin Lipoderm® formulation were able to facilitate permeation of the molecule across human skin. Further pre-clinical and clinical studies are required to investigate the topical delivery performance and pharmacodynamic actions of prospective formulations. PMID:28867811

Prediction of helicopter rotor discrete frequency noise: A computer program incorporating realistic blade motions and advanced acoustic formulation

NASA Technical Reports Server (NTRS)

Brentner, K. S.

1986-01-01

A computer program has been developed at the Langley Research Center to predict the discrete frequency noise of conventional and advanced helicopter rotors. The program, called WOPWOP, uses the most advanced subsonic formulation of Farassat that is less sensitive to errors and is valid for nearly all helicopter rotor geometries and flight conditions. A brief derivation of the acoustic formulation is presented along with a discussion of the numerical implementation of the formulation. The computer program uses realistic helicopter blade motion and aerodynamic loadings, input by the user, for noise calculation in the time domain. A detailed definition of all the input variables, default values, and output data is included. A comparison with experimental data shows good agreement between prediction and experiment; however, accurate aerodynamic loading is needed.

Polynomial Size Formulations for the Distance and Capacity Constrained Vehicle Routing Problem

NASA Astrophysics Data System (ADS)

Kara, Imdat; Derya, Tusan

2011-09-01

The Distance and Capacity Constrained Vehicle Routing Problem (DCVRP) is an extension of the well known Traveling Salesman Problem (TSP). DCVRP arises in distribution and logistics problems. It would be beneficial to construct new formulations, which is the main motivation and contribution of this paper. We focused on two indexed integer programming formulations for DCVRP. One node based and one arc (flow) based formulation for DCVRP are presented. Both formulations have O(n2) binary variables and O(n2) constraints, i.e., the number of the decision variables and constraints grows with a polynomial function of the nodes of the underlying graph. It is shown that proposed arc based formulation produces better lower bound than the existing one (this refers to the Water's formulation in the paper). Finally, various problems from literature are solved with the node based and arc based formulations by using CPLEX 8.0. Preliminary computational analysis shows that, arc based formulation outperforms the node based formulation in terms of linear programming relaxation.

Environmental fate and effects of granular pesta formulation from strains of Pseudomonas aeruginosa C1501 and Lasiodiplodia pseudotheobromae C1136 on soil activity and weeds.

PubMed

Adetunji, Charles Oluwaseun; Oloke, Julius Kola; Osemwegie, Osarenkhoe Omorefosa

2018-03-01

This work investigated the effect of variably formulated pesta granules containing wild and UV mutated Pseudomonas aeruginosa and Lasiodiplodia pseudotheobromae on the rate of CO 2 evolution, organic carbon content, enzymatic activity (acidic and alkaline phosphatase, dehydrogenases, urease and protease) and representative soil microorganisms in the soils using different assay techniques. After the 35th day period of experiment, the pesta granule formulation BH4 showed the best evolution of CO 2 (824 ± 6.2 mg CO 2 kg -1 soil hr -1 ) as against control treatment (689 ± 3.7 mg CO 2 kg -1 soil hr -1 ). Enzymes activities, organic carbon content of 3.8% on the 15th day of study and stable representation of microorganisms that include actinomycetes, fungi, heterogenous as well as soil nitrogen-mediatory bacteria were equally at their maximum level BH4 treatments. The phytotoxic assay showed no inhibitory effect on Solanum lycopersicum seeds and seedlings compared to the observed growth inhibition on the tested weeds (Amaranthus hybridus and Echinocholoa crus-galli) which corresponds with positive control glyphosate treatment. The glyphosate treated soil had the least critical results on parameters investigated during the study. The order of bioherbicidal activity is BH4>BH2>BH6>BH3>BH1>BH5>positive control. Results from this study confirmed the target efficacy of variably formulated pesta granules which is sustainable, cheap, ecologically suitable and recent. This is in addition to recognizing the microbial-derived formulations as characteristically potent alternative to chemical herbicides utility in agrosystems practice. Further study of the underlining factor responsible for the bioherbicidal performances of the variably formulated pesta granules and field trials are critical for their future commercialization. Copyright © 2017 Elsevier Ltd. All rights reserved.

A two-field modified Lagrangian formulation for robust simulations of extrinsic cohesive zone models

NASA Astrophysics Data System (ADS)

Cazes, F.; Coret, M.; Combescure, A.

2013-06-01

This paper presents the robust implementation of a cohesive zone model based on extrinsic cohesive laws (i.e. laws involving an infinite initial stiffness). To this end, a two-field Lagrangian weak formulation in which cohesive tractions are chosen as the field variables along the crack's path is presented. Unfortunately, this formulation cannot model the infinite compliance of the broken elements accurately, and no simple criterion can be defined to determine the loading-unloading change of state at the integration points of the cohesive elements. Therefore, a modified Lagrangian formulation using a fictitious cohesive traction instead of the classical cohesive traction as the field variable is proposed. Thanks to this change of variable, the cohesive law becomes an increasing function of the equivalent displacement jump, which eliminates the problems mentioned previously. The ability of the proposed formulations to simulate fracture accurately and without field oscillations is investigated through three numerical test examples.

Use of multi-node wells in the Groundwater-Management Process of MODFLOW-2005 (GWM-2005)

USGS Publications Warehouse

Ahlfeld, David P.; Barlow, Paul M.

2013-01-01

Many groundwater wells are open to multiple aquifers or to multiple intervals within a single aquifer. These types of wells can be represented in numerical simulations of groundwater flow by use of the Multi-Node Well (MNW) Packages developed for the U.S. Geological Survey’s MODFLOW model. However, previous versions of the Groundwater-Management (GWM) Process for MODFLOW did not allow the use of multi-node wells in groundwater-management formulations. This report describes modifications to the MODFLOW–2005 version of the GWM Process (GWM–2005) to provide for such use with the MNW2 Package. Multi-node wells can be incorporated into a management formulation as flow-rate decision variables for which optimal withdrawal or injection rates will be determined as part of the GWM–2005 solution process. In addition, the heads within multi-node wells can be used as head-type state variables, and, in that capacity, be included in the objective function or constraint set of a management formulation. Simple head bounds also can be defined to constrain water levels at multi-node wells. The report provides instructions for including multi-node wells in the GWM–2005 data-input files and a sample problem that demonstrates use of multi-node wells in a typical groundwater-management problem.

VALIDITY OF A TWO-DIMENSIONAL MODEL FOR VARIABLE-DENSITY HYDRODYNAMIC CIRCULATION

EPA Science Inventory

A three-dimensional model of temperatures and currents has been formulated to assist in the analysis and interpretation of the dynamics of stratified lakes. In this model, nonlinear eddy coefficients for viscosity and conductivities are included. A two-dimensional model (one vert...

Isogeometric analysis of free-form Timoshenko curved beams including the nonlinear effects of large deformations

NASA Astrophysics Data System (ADS)

Hosseini, Seyed Farhad; Hashemian, Ali; Moetakef-Imani, Behnam; Hadidimoud, Saied

2018-03-01

In the present paper, the isogeometric analysis (IGA) of free-form planar curved beams is formulated based on the nonlinear Timoshenko beam theory to investigate the large deformation of beams with variable curvature. Based on the isoparametric concept, the shape functions of the field variables (displacement and rotation) in a finite element analysis are considered to be the same as the non-uniform rational basis spline (NURBS) basis functions defining the geometry. The validity of the presented formulation is tested in five case studies covering a wide range of engineering curved structures including from straight and constant curvature to variable curvature beams. The nonlinear deformation results obtained by the presented method are compared to well-established benchmark examples and also compared to the results of linear and nonlinear finite element analyses. As the nonlinear load-deflection behavior of Timoshenko beams is the main topic of this article, the results strongly show the applicability of the IGA method to the large deformation analysis of free-form curved beams. Finally, it is interesting to notice that, until very recently, the large deformations analysis of free-form Timoshenko curved beams has not been considered in IGA by researchers.

Simultaneous Optimization of Multiple Response Variables for the Gelatin-chitosan Microcapsules Containing Angelica Essential Oil.

PubMed

Li, Qiang; Sun, Li-Jian; Gong, Xian-Feng; Wang, Yang; Zhao, Xue-Ling

2017-01-01

Angelica essential oil (AO), a major pharmacologically active component of Angelica sinensis (Oliv.) Diels, possesses hemogenesis, analgesic activities, and sedative effect. The application of AO in pharmaceutical systems had been limited because of its low oxidative stability. The AO-loaded gelatin-chitosan microcapsules with prevention from oxidation were developed and optimized using response surface methodology. The effects of formulation variables (pH at complex coacervation, gelatin concentration, and core/wall ratio) on multiple response variables (yield, encapsulation efficiency, antioxidation rate, percent of drug released in 1 h, and time to 85% drug release) were systemically investigated. A desirability function that combined these five response variables was constructed. All response variables investigated were found to be highly dependent on the formulation variables, with strong interactions observed between the formulation variables. It was found that optimum overall desirability of AO microcapsules could be obtained at pH 6.20, gelatin concentration 25.00%, and core/wall ratio 40.40%. The experimental values of the response variables highly agreed with the predicted values. The antioxidation rate of optimum formulation was approximately 8 times higher than that of AO. The in-vitro drug release from microcapsules was followed Higuchi model with super case-II transport mechanism.

An analytical formulation of two‐dimensional groundwater dispersion induced by surficial recharge variability

USGS Publications Warehouse

Swain, Eric D.; Chin, David A.

2003-01-01

A predominant cause of dispersion in groundwater is advective mixing due to variability in seepage rates. Hydraulic conductivity variations have been extensively researched as a cause of this seepage variability. In this paper the effect of variations in surface recharge to a shallow surficial aquifer is investigated as an important additional effect. An analytical formulation has been developed that relates aquifer parameters and the statistics of recharge variability to increases in the dispersivity. This is accomplished by solving Fourier transforms of the small perturbation forms of the groundwater flow equations. Two field studies are presented in this paper to determine the statistics of recharge variability for input to the analytical formulation. A time series of water levels at a continuous groundwater recorder is used to investigate the temporal statistics of hydraulic head caused by recharge, and a series of infiltrometer measurements are used to define the spatial variability in the recharge parameters. With these field statistics representing head fluctuations due to recharge, the analytical formulation can be used to compute the dispersivity without an explicit representation of the recharge boundary. Results from a series of numerical experiments are used to define the limits of this analytical formulation and to provide some comparison. A sophisticated model has been developed using a particle‐tracking algorithm (modified to account for temporal variations) to estimate groundwater dispersion. Dispersivity increases of 9 percent are indicated by the analytical formulation for the aquifer at the field site. A comparison with numerical model results indicates that the analytical results are reasonable for shallow surficial aquifers in which two‐dimensional flow can be assumed.

The Analysis, Numerical Simulation, and Diagnosis of Extratropical Weather Systems

DTIC Science & Technology

1999-09-30

The Analysis, Numerical Simulation, and Diagnosis of Extratropical Weather Systems Dr. Melvyn A. Shapiro NOAA/Environmental Technology Laboratory...formulation, and numerical prediction of the life cycles of synoptic-scale and mesoscale extratropical weather systems, including the influence of planetary...scale inter-annual and intra-seasonal variability on their evolution. These weather systems include: extratropical oceanic and land-falling cyclones

The application of the Routh approximation method to turbofan engine models

NASA Technical Reports Server (NTRS)

Merrill, W. C.

1977-01-01

The Routh approximation technique is applied in the frequency domain to a 16th order state variable turbofan engine model. The results obtained motivate the extension of the frequency domain formulation of the Routh method to the time domain to handle the state variable formulation directly. The time domain formulation is derived, and a characterization, which specifies all possible Routh similarity transformations, is given. The characterization is computed by the solution of two eigenvalue eigenvector problems. The application of the time domain Routh technique to the state variable engine model is described, and some results are given.

Buckling Analysis of Anisotropic Curved Panels and Shells with Variable Curvature

NASA Technical Reports Server (NTRS)

Jaunky, Navin; Knight, Norman F., Jr.; Ambur, Damodar R.

1998-01-01

A buckling formulation for anisotropic curved panels with variable curvature is presented in this paper. The variable curvature panel is assumed to consists of two or more panels of constant but different curvatures. Bezier functions are used as Ritz functions Displacement (C(sup 0)), and slope (C(sup 1)) continuities between segments are imposed by manipulation of the Bezier control points. A first-order shear-deformation theory is used in the buckling formulation. Results obtained from the present formulation are compared with those from finite element simulations and are found to be in good agreement.

[Optimization of formulations for dietetic pastry products].

PubMed

Villarroel, M; Uquiche, E; Brito, G; Cancino, M

2000-03-01

Optimized formulations of dietetic pastry products such as cake and sponge cake premixes were formulated using the surface response methodology. % Emulsifier agent and baking time were the selected independent variables for cake, as well as % emulsifier agent % chlorinated flour the variables selected for sponge cake. Three different level of each variable summing up thirteen experimental formulae of each product were assessed to optimize the variables that could have some influence in the sensory characteristics of these dietetic products. The total sensory quality was determined for both dietetic products using the composite scoring test and a panel of 18 trained judges. Looking at the contour graphic and considering economic aspects the best combination of variables for cake formulation was 2% emulsifier agent and 48 minutes for baking time, With respect to sponge cake, the best combination was 6% emulsifier agent and 48% chlorinated flour. Shelf life studies showed that both dietetic formulations remained stable during storage conditions of 75 days at 30 degrees C. During this period, significant differences in sensory characteristics were not found (p < 0.05). Data of peroxide values were kept under the critical value reported for detection of organoleptic rancidity. Reported values of hedonic test showed that these dietetics pastry products had good acceptability, and open up marketing opportunities for new products with potential health benefits to consumers.

Le Châtelier reciprocal relations and the mechanical analog

NASA Astrophysics Data System (ADS)

Gilmore, Robert

1983-08-01

Le Châtelier's principle is discussed carefully in terms of two sets of simple thermodynamic examples. The principle is then formulated quantitatively for general thermodynamic systems. The formulation is in terms of a perturbation-response matrix, the Le Châtelier matrix [L]. Le Châtelier's principle is contained in the diagonal elements of this matrix, all of which exceed one. These matrix elements describe the response of a system to a perturbation of either its extensive or intensive variables. These response ratios are inverses of each other. The Le Châtelier matrix is symmetric, so that a new set of thermodynamic reciprocal relations is derived. This quantitative formulation is illustrated by a single simple example which includes the original examples and shows the reciprocities among them. The assumptions underlying this new quantitative formulation of Le Châtelier's principle are general and applicable to a wide variety of nonthermodynamic systems. Le Châtelier's principle is formulated quantitatively for mechanical systems in static equilibrium, and mechanical examples of this formulation are given.

State-constrained booster trajectory solutions via finite elements and shooting

NASA Technical Reports Server (NTRS)

Bless, Robert R.; Hodges, Dewey H.; Seywald, Hans

1993-01-01

This paper presents an extension of a FEM formulation based on variational principles. A general formulation for handling internal boundary conditions and discontinuities in the state equations is presented, and the general formulation is modified for optimal control problems subject to state-variable inequality constraints. Solutions which only touch the state constraint and solutions which have a boundary arc of finite length are considered. Suitable shape and test functions are chosen for a FEM discretization. All element quadrature (equivalent to one-point Gaussian quadrature over each element) may be done in closed form. The final form of the algebraic equations is then derived. A simple state-constrained problem is solved. Then, for a practical application of the use of the FEM formulation, a launch vehicle subject to a dynamic pressure constraint (a first-order state inequality constraint) is solved. The results presented for the launch-vehicle trajectory have some interesting features, including a touch-point solution.

Formulation for Simultaneous Aerodynamic Analysis and Design Optimization

NASA Technical Reports Server (NTRS)

Hou, G. W.; Taylor, A. C., III; Mani, S. V.; Newman, P. A.

1993-01-01

An efficient approach for simultaneous aerodynamic analysis and design optimization is presented. This approach does not require the performance of many flow analyses at each design optimization step, which can be an expensive procedure. Thus, this approach brings us one step closer to meeting the challenge of incorporating computational fluid dynamic codes into gradient-based optimization techniques for aerodynamic design. An adjoint-variable method is introduced to nullify the effect of the increased number of design variables in the problem formulation. The method has been successfully tested on one-dimensional nozzle flow problems, including a sample problem with a normal shock. Implementations of the above algorithm are also presented that incorporate Newton iterations to secure a high-quality flow solution at the end of the design process. Implementations with iterative flow solvers are possible and will be required for large, multidimensional flow problems.

Fatigue life prediction of rotor blade composites: Validation of constant amplitude formulations with variable amplitude experiments

NASA Astrophysics Data System (ADS)

Westphal, T.; Nijssen, R. P. L.

2014-12-01

The effect of Constant Life Diagram (CLD) formulation on the fatigue life prediction under variable amplitude (VA) loading was investigated based on variable amplitude tests using three different load spectra representative for wind turbine loading. Next to the Wisper and WisperX spectra, the recently developed NewWisper2 spectrum was used. Based on these variable amplitude fatigue results the prediction accuracy of 4 CLD formulations is investigated. In the study a piecewise linear CLD based on the S-N curves for 9 load ratios compares favourably in terms of prediction accuracy and conservativeness. For the specific laminate used in this study Boerstra's Multislope model provides a good alternative at reduced test effort.

Quality by Design approach for studying the impact of formulation and process variables on product quality of oral disintegrating films.

PubMed

Mazumder, Sonal; Pavurala, Naresh; Manda, Prashanth; Xu, Xiaoming; Cruz, Celia N; Krishnaiah, Yellela S R

2017-07-15

The present investigation was carried out to understand the impact of formulation and process variables on the quality of oral disintegrating films (ODF) using Quality by Design (QbD) approach. Lamotrigine (LMT) was used as a model drug. Formulation variable was plasticizer to film former ratio and process variables were drying temperature, air flow rate in the drying chamber, drying time and wet coat thickness of the film. A Definitive Screening Design of Experiments (DoE) was used to identify and classify the critical formulation and process variables impacting critical quality attributes (CQA). A total of 14 laboratory-scale DoE formulations were prepared and evaluated for mechanical properties (%elongation at break, yield stress, Young's modulus, folding endurance) and other CQA (dry thickness, disintegration time, dissolution rate, moisture content, moisture uptake, drug assay and drug content uniformity). The main factors affecting mechanical properties were plasticizer to film former ratio and drying temperature. Dissolution rate was found to be sensitive to air flow rate during drying and plasticizer to film former ratio. Data were analyzed for elucidating interactions between different variables, rank ordering the critical materials attributes (CMA) and critical process parameters (CPP), and for providing a predictive model for the process. Results suggested that plasticizer to film former ratio and process controls on drying are critical to manufacture LMT ODF with the desired CQA. Published by Elsevier B.V.

Quality by design approach for understanding the critical quality attributes of cyclosporine ophthalmic emulsion.

PubMed

Rahman, Ziyaur; Xu, Xiaoming; Katragadda, Usha; Krishnaiah, Yellela S R; Yu, Lawrence; Khan, Mansoor A

2014-03-03

Restasis is an ophthalmic cyclosporine emulsion used for the treatment of dry eye syndrome. There are no generic products for this product, probably because of the limitations on establishing in vivo bioequivalence methods and lack of alternative in vitro bioequivalence testing methods. The present investigation was carried out to understand and identify the appropriate in vitro methods that can discriminate the effect of formulation and process variables on critical quality attributes (CQA) of cyclosporine microemulsion formulations having the same qualitative (Q1) and quantitative (Q2) composition as that of Restasis. Quality by design (QbD) approach was used to understand the effect of formulation and process variables on critical quality attributes (CQA) of cyclosporine microemulsion. The formulation variables chosen were mixing order method, phase volume ratio, and pH adjustment method, while the process variables were temperature of primary and raw emulsion formation, microfluidizer pressure, and number of pressure cycles. The responses selected were particle size, turbidity, zeta potential, viscosity, osmolality, surface tension, contact angle, pH, and drug diffusion. The selected independent variables showed statistically significant (p < 0.05) effect on droplet size, zeta potential, viscosity, turbidity, and osmolality. However, the surface tension, contact angle, pH, and drug diffusion were not significantly affected by independent variables. In summary, in vitro methods can detect formulation and manufacturing changes and would thus be important for quality control or sameness of cyclosporine ophthalmic products.

Formulation Optimization of Human Insulin Loaded Microspheres for Controlled Oral Delivery Using Response Surface Methodology.

PubMed

Agrawal, Gauravkuma; Wakte, Pravin; Shelke, Santosh

2017-01-01

The objectives of the present investigation were to prepare recombinant human insulin entrapped Eudragit-S100 microspheres containing protease inhibitors and to precisely analyze the outcome of different formulation variables on the microspheres properties using a response surface methodology to develop an optimized formulation with desirable features. A central composite design was employed to produce microspheres of therapeutic protein by w/o/w multiple emulsion solvent evaporation technique using Eudragit S-100 as coating material and polyvinyl alcohol as a stabilizer. The effect of formulation variables (independent variables) that is levels of Eudragit S-100 (X1), therapeutic protein (X2), volumes of inner aqueous phase (X3) and external aqueous phase (X4) on dependant variables, that are encapsulation efficiency (Y1), drug release at pH 1.2 after 2 h (Y2) and drug release at pH 7.4 after of 2 h (Y3) were evaluated. The significant terms in the mathematical models were generated for each response parameter using multiple linear regression analysis and analysis of variance. All the formulation variables except the volume of external aqueous phase (X4) exerted a significant effect (P <0.05) on drug encapsulation efficiency (Y1) whereas first two variables, namely the levels of Eudragit S-100 (X1) and therapeutic protein (X2) materialized as the determining factors which significantly influenced drug release at pH 1.2 after 2 h (Y2) and drug release at pH 7.4 after of 2 h (Y3). The formulation was numerically optimized by framing the constraints on the dependent and independent variables using the desirability approach. The experimental values for Y1 and Y2 of optimized formulation were found to be 77.65% and 3.64%, respectively which were quite closer to results suggested by software. The results recorded indicate that the recombinant human insulin loaded Eudragit S-100 microspheres containing aprotinin have the benefits of higher loading efficiency, pH responsive and prolonged release characteristics, which may help to carry insulin to the optimum site of absorption. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Understanding effect of formulation and manufacturing variables on the critical quality attributes of warfarin sodium product.

PubMed

Rahman, Ziyaur; Korang-Yeboah, Maxwell; Siddiqui, Akhtar; Mohammad, Adil; Khan, Mansoor A

2015-11-10

Warfarin sodium (WS) is a narrow therapeutic index drug and its product quality should be thoroughly understood and monitored in order to avoid clinical performance issues. This study was focused on understanding the effect of manufacturing and formulation variables on WS product critical quality attributes (CQAs). Eight formulations were developed with lactose monohydrate (LM) or lactose anhydrous (LA), and were either wet granulated or directly compressed. Formulations were granulated either with ethanol, isopropyl alcohol (IPA) and IPA-water mixture (50:50). Formulations were characterized for IPA, water content, hardness, disintegration time (DT), assay, dissolution and drug physical forms (scanning electron microscopy (SEM), near infrared chemical imaging (NIR-CI), X-ray powder diffraction (XRPD) and solid state nuclear magnetic resonance (ssNMR)), and performed accelerated stability studies at 40°C/75% RH for three days. The DT and dissolution of directly compressed formulations were faster than wet granulated formulations. This was due to phase transformation of crystalline drug into its amorphous form as indicated by SEM, NIR-CI, XRPD and ssNMR data which itself act as a binder. Similarly, LM showed faster disintegration and dissolution than LA containing formulations. Stability results indicated an increase in hardness and DT, and a decrease in dissolution rate and extent. This was due to phase transformation of the drug and consolidation with particles' bonding. In conclusion, the CQAs of WS product were significantly affected by manufacturing and formulation variables. Published by Elsevier B.V.

Enhanced model of gear transmission dynamics for condition monitoring applications: Effects of torque, friction and bearing clearance

NASA Astrophysics Data System (ADS)

Fernandez-del-Rincon, A.; Garcia, P.; Diez-Ibarbia, A.; de-Juan, A.; Iglesias, M.; Viadero, F.

2017-02-01

Gear transmissions remain as one of the most complex mechanical systems from the point of view of noise and vibration behavior. Research on gear modeling leading to the obtaining of models capable of accurately reproduce the dynamic behavior of real gear transmissions has spread out the last decades. Most of these models, although useful for design stages, often include simplifications that impede their application for condition monitoring purposes. Trying to filling this gap, the model presented in this paper allows us to simulate gear transmission dynamics including most of these features usually neglected by the state of the art models. This work presents a model capable of considering simultaneously the internal excitations due to the variable meshing stiffness (including the coupling among successive tooth pairs in contact, the non-linearity linked with the contacts between surfaces and the dissipative effects), and those excitations consequence of the bearing variable compliance (including clearances or pre-loads). The model can also simulate gear dynamics in a realistic torque dependent scenario. The proposed model combines a hybrid formulation for calculation of meshing forces with a non-linear variable compliance approach for bearings. Meshing forces are obtained by means of a double approach which combines numerical and analytical aspects. The methodology used provides a detailed description of the meshing forces, allowing their calculation even when gear center distance is modified due to shaft and bearing flexibilities, which are unavoidable in real transmissions. On the other hand, forces at bearing level were obtained considering a variable number of supporting rolling elements, depending on the applied load and clearances. Both formulations have been developed and applied to the simulation of the vibration of a sample transmission, focusing the attention on the transmitted load, friction meshing forces and bearing preloads.

Tolerance of entomopathogenic fungi to ultraviolet radiation: a review on screening of strains and their formulation.

PubMed

Fernandes, Éverton K K; Rangel, Drauzio E N; Braga, Gilberto U L; Roberts, Donald W

2015-08-01

Ultraviolet radiation from sunlight is probably the most detrimental environmental factor affecting the viability of entomopathogenic fungi applied to solar-exposed sites (e.g., leaves) for pest control. Most entomopathogenic fungi are sensitive to UV radiation, but there is great inter- and intraspecies variability in susceptibility to UV. This variability may reflect natural adaptations of isolates to their different environmental conditions. Selecting strains with outstanding natural tolerance to UV is considered as an important step to identify promising biological control agents. However, reports on tolerance among the isolates used to date must be analyzed carefully due to considerable variations in the methods used to garner the data. The current review presents tables listing many studies in which different methods were applied to check natural and enhanced tolerance to UV stress of numerous entomopathogenic fungi, including several well-known isolates of these fungi. The assessment of UV tolerance is usually conducted with conidia using dose-response methods, wherein the UV dose is calculated simply by multiplying the total irradiance by the period (time) of exposure. Although irradiation from lamps seldom presents an environmentally realistic spectral distribution, laboratory tests circumvent the uncontrollable circumstances associated with field assays. Most attempts to increase field persistence of microbial agents have included formulating conidia with UV protectants; however, in many cases, field efficacy of formulated fungi is still not fully adequate for dependable pest control.

Optimization and design of ibuprofen-loaded nanostructured lipid carriers using a hybrid-design approach for ocular drug delivery

NASA Astrophysics Data System (ADS)

Rathod, Vishal

The objective of the present project was to develop the Ibuprofen-loaded Nanostructured Lipid Carrier (IBU-NLCs) for topical ocular delivery based on substantial pre-formulation screening of the components and understanding the interplay between the formulation and process variables. The BCS Class II drug: Ibuprofen was selected as the model drug for the current study. IBU-NLCs were prepared by melt emulsification and ultrasonication technique. Extensive pre-formulation studies were performed to screen the lipid components (solid and liquid) based on drug's solubility and affinity as well as components compatibility. The results from DSC & XRD assisted in selecting the most suitable ratio to be utilized for future studies. DynasanRTM 114 was selected as the solid lipid & MiglyolRTM 840 was selected as the liquid lipid based on preliminary lipid screening. The ratio of 6:4 was predicted to be the best based on its crystallinity index and the thermal events. As there are many variables involved for further optimization of the formulation, a single design approach is not always adequate. A hybrid-design approach was applied by employing the Plackett Burman design (PBD) for preliminary screening of 7 critical variables, followed by Box-Behnken design (BBD), a sub-type of response surface methodology (RSM) design using 2 relatively significant variables from the former design and incorporating Surfactant/Co-surfactant ratio as the third variable. Comparatively, KolliphorRTM HS15 demonstrated lower Mean Particle Size (PS) & Polydispersity Index (PDI) and KolliphorRTM P188 resulted in Zeta Potential (ZP) < -20 mV during the surfactant screening & stability studies. Hence, Surfactant/Cosurfactant ratio was employed as the third variable to understand its synergistic effect on the response variables. We selected PS, PDI, and ZP as critical response variables in the PBD since they significantly influence the stability & performance of NLCs. Formulations prepared using BBD were further characterized and evaluated concerning PS, PDI, ZP and Entrapment Efficiency (EE) to identify the multi-factor interactions between selected formulation variables. In vitro release studies were performed using Spectra/por dialysis membrane on Franz diffusion cell and Phosphate Saline buffer (7.4 pH) as the medium. Samples for assay, EE, Loading Capacity (LC), Solubility studies & in-vitro release were filtered using Amicon 50K and analyzed via UPLC system (Waters) at a detection wavelength of 220 nm. Significant variables were selected through PBD, and the third variable was incorporated based on surfactant screening & stability studies for the next design. Assay of the BBD based formulations was found to be within 95-104% of the theoretically calculated values. Further studies were investigated for PS, PDI, ZP & EE. PS was found to be in the range of 103-194 nm with PDI ranging from 0.118 to 0.265. The ZP and EE were observed to be in the range of -22.2 to -11 mV & 90 to 98.7 % respectively. Drug release of 30% was observed from the optimized formulation in the first 6 hr of in-vitro studies, and the drug release showed a sustained release of ibuprofen thereafter over several hours. These values also confirm that the production method, and all other selected variables, effectively promoted the incorporation of ibuprofen in NLC. Quality by Design (QbD) approach was successfully implemented in developing a robust ophthalmic formulation with superior physicochemical and morphometric properties. NLCs as the nanocarrier demonstrated promising perspective for topical delivery of poorly water-soluble drugs.

Application of multi-block analysis and mixture design with process variable for development of chocolate cake containing yacon (Smallanthus sonchifolius) and maca (Lepidium meyenii).

PubMed

Tormena, Marcela Marta Lazaretti; de Medeiros, Luana Tabalipa; de Lima, Patrícia Casarin; Possebon, Gabriela; Fuchs, Renata Hernandez Barros; Bona, Evandro

2017-08-01

In this study, a chocolate cake formulation was developed with partial substitution of wheat flour by yacon and maca flour. A simplex-centroid design was applied to determine the proportions of the three flours, and the amount of water was included as a process variable at three distinct levels. According to the overall acceptability of the cakes, the tasters were separated into two groups using k-means. After segmentation, regression models were constructed for overall acceptability of each group; R 2 adjusted values of 92.5% for group 1 and 98.9% for group 2 were obtained. Using the sequential simplex method an optimized formulation was determined for group 1 (0.49 kg wheat kg -1 total flour , 0.37 kg yacon kg -1 total flour , 0.14 kg maca kg -1 total flour and 140.0 mL of water) and another for group 2 (0.35 kg wheat kg -1 total flour , 0.65 kg yacon kg -1 total flour and 120.0 mL of water). In addition to these formulations, a third formulation was proposed with a greater maca proportion (0.32 kg maca kg -1 total flour ), which does not significantly alter the overall acceptability of both groups. The three optimized formulations and two control formulations were evaluated through free-choice profiling. The data were evaluated using the multi-block method common components and specific weights analysis (CCSWA). It was observed that a greater proportion of maca intensified brownness and burnt aroma and taste, whereas a larger proportion of yacon produced a better appearance, softness, sweetness and chocolate flavor. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Examining Preservice Science Teachers' Skills of Formulating Hypotheses and Identifying Variables

ERIC Educational Resources Information Center

Aydogdu, Bülent

2015-01-01

The aim of this study is to examine preservice science teachers' skills of formulating hypotheses and identifying variables. The research has a phenomenological research design. The data was gathered qualitatively. In this study, preservice science teachers were first given two scenarios (Scenario-1 & Scenario-2) containing two different…

The contribution of spray formulation component variables to foliar uptake of agrichemicals.

PubMed

Forster, W Alison; Kimberley, Mark O

2015-09-01

The objective of the present study was to determine the contribution of the active ingredient (AI) and surfactant, and their concentrations, to the foliar uptake of agrichemicals, and to examine the physical properties that would need to be included in a model for foliar uptake. All spray formulation component variables significantly affected uptake, explaining 73% of the deviance. The deviance explained by each factor ranged from 43% (AI concentration nested within AI) to 5.6% (surfactant). The only significant interaction was between AI and surfactant, explaining 15.8% of the deviance. Overall, 90% of the deviance could be explained by the variables and their first-order interactions. Uptake increased with increasing lipophilicity of the AI at concentrations below those causing precipitation on the leaf surface. AI concentration had a far greater (negative) effect on the uptake of the lipophilic molecule epoxiconazole. The uptake of 2-deoxy-D-glucose (DOG) and 2,4-dichlorophenoxyacetic acid (2,4-D) increased with increasing hydrophile-lipophile balance (HLB) of the surfactant, the effect of HLB being far greater on the hydrophilic molecule DOG. However, the differences observed in epoxiconazole uptake owing to the surfactant were strongly positively related to the spread area of the formulation on the leaf surface. For all AIs, uptake increased in a similar manner with increasing molar surfactant concentration. © 2014 Society of Chemical Industry.

Formulation and statistical optimization of self-microemulsifying drug delivery system of eprosartan mesylate for improvement of oral bioavailability.

PubMed

Dangre, Pankaj; Gilhotra, Ritu; Dhole, Shashikant

2016-10-01

The present investigation is aimed to design a statistically optimized self-microemulsifying drug delivery system (SMEDDS) of eprosartan mesylate (EM). Preliminary screening was carried out to find a suitable combination of various excipients for the formulation. A 3(2) full factorial design was employed to determine the effect of various independent variables on dependent (response) variables. The independent variables studied in the present work were concentration of oil (X 1) and the ratio of S mix (X 2), whereas the dependent variables were emulsification time (s), globule size (nm), polydispersity index (pdi), and zeta potential (mV), and the multiple linear regression analysis (MLRA) was employed to understand the influence of independent variables on dependent variables. Furthermore, a numerical optimization technique using the desirability function was used to develop a new optimized formulation with desired values of dependent variables. The optimized SMEDDS formulation of eprosartan mesylate (EMF-O) by the above method exhibited emulsification time, 118.45 ± 1.64 s; globule size, 196.81 ± 1.29 nm; zeta potential, -9.34 ± 1.2 mV, and polydispersity index, 0.354 ± 0.02. For the in vitro dissolution study, the optimized formulation (EMF-O) and pure drug were separately entrapped in the dialysis bag, and the study indicated higher release of the drug from EMF-O. In vivo pharmacokinetic studies in Wistar rats using PK solver software revealed 2.1-fold increment in oral bioavailability of EM from EMF-O, when compared with plain suspension of pure drug.

Smoothed Particle Hydrodynamics Simulations of Ultrarelativistic Shocks with Artificial Viscosity

NASA Astrophysics Data System (ADS)

Siegler, S.; Riffert, H.

2000-03-01

We present a fully Lagrangian conservation form of the general relativistic hydrodynamic equations for perfect fluids with artificial viscosity in a given arbitrary background spacetime. This conservation formulation is achieved by choosing suitable Lagrangian time evolution variables, from which the generic fluid variables of rest-mass density, 3-velocity, and thermodynamic pressure have to be determined. We present the corresponding equations for an ideal gas and show the existence and uniqueness of the solution. On the basis of the Lagrangian formulation we have developed a three-dimensional general relativistic smoothed particle hydrodynamics (SPH) code using the standard SPH formalism as known from nonrelativistic fluid dynamics. One-dimensional simulations of a shock tube and a wall shock are presented together with a two-dimensional test calculation of an inclined shock tube. With our method we can model ultrarelativistic fluid flows including shocks with Lorentz factors of even 1000.

Application of Multivariate Modeling for Radiation Injury Assessment: A Proof of Concept

PubMed Central

Bolduc, David L.; Villa, Vilmar; Sandgren, David J.; Ledney, G. David; Blakely, William F.; Bünger, Rolf

2014-01-01

Multivariate radiation injury estimation algorithms were formulated for estimating severe hematopoietic acute radiation syndrome (H-ARS) injury (i.e., response category three or RC3) in a rhesus monkey total-body irradiation (TBI) model. Classical CBC and serum chemistry blood parameters were examined prior to irradiation (d 0) and on d 7, 10, 14, 21, and 25 after irradiation involving 24 nonhuman primates (NHP) (Macaca mulatta) given 6.5-Gy 60Co Υ-rays (0.4 Gy min−1) TBI. A correlation matrix was formulated with the RC3 severity level designated as the “dependent variable” and independent variables down selected based on their radioresponsiveness and relatively low multicollinearity using stepwise-linear regression analyses. Final candidate independent variables included CBC counts (absolute number of neutrophils, lymphocytes, and platelets) in formulating the “CBC” RC3 estimation algorithm. Additionally, the formulation of a diagnostic CBC and serum chemistry “CBC-SCHEM” RC3 algorithm expanded upon the CBC algorithm model with the addition of hematocrit and the serum enzyme levels of aspartate aminotransferase, creatine kinase, and lactate dehydrogenase. Both algorithms estimated RC3 with over 90% predictive power. Only the CBC-SCHEM RC3 algorithm, however, met the critical three assumptions of linear least squares demonstrating slightly greater precision for radiation injury estimation, but with significantly decreased prediction error indicating increased statistical robustness. PMID:25165485

Strong diffusion formulation of Markov chain ensembles and its optimal weaker reductions

NASA Astrophysics Data System (ADS)

Güler, Marifi

2017-10-01

Two self-contained diffusion formulations, in the form of coupled stochastic differential equations, are developed for the temporal evolution of state densities over an ensemble of Markov chains evolving independently under a common transition rate matrix. Our first formulation derives from Kurtz's strong approximation theorem of density-dependent Markov jump processes [Stoch. Process. Their Appl. 6, 223 (1978), 10.1016/0304-4149(78)90020-0] and, therefore, strongly converges with an error bound of the order of lnN /N for ensemble size N . The second formulation eliminates some fluctuation variables, and correspondingly some noise terms, within the governing equations of the strong formulation, with the objective of achieving a simpler analytic formulation and a faster computation algorithm when the transition rates are constant or slowly varying. There, the reduction of the structural complexity is optimal in the sense that the elimination of any given set of variables takes place with the lowest attainable increase in the error bound. The resultant formulations are supported by numerical simulations.

A variable-gain output feedback control design methodology

NASA Technical Reports Server (NTRS)

Halyo, Nesim; Moerder, Daniel D.; Broussard, John R.; Taylor, Deborah B.

1989-01-01

A digital control system design technique is developed in which the control system gain matrix varies with the plant operating point parameters. The design technique is obtained by formulating the problem as an optimal stochastic output feedback control law with variable gains. This approach provides a control theory framework within which the operating range of a control law can be significantly extended. Furthermore, the approach avoids the major shortcomings of the conventional gain-scheduling techniques. The optimal variable gain output feedback control problem is solved by embedding the Multi-Configuration Control (MCC) problem, previously solved at ICS. An algorithm to compute the optimal variable gain output feedback control gain matrices is developed. The algorithm is a modified version of the MCC algorithm improved so as to handle the large dimensionality which arises particularly in variable-gain control problems. The design methodology developed is applied to a reconfigurable aircraft control problem. A variable-gain output feedback control problem was formulated to design a flight control law for an AFTI F-16 aircraft which can automatically reconfigure its control strategy to accommodate failures in the horizontal tail control surface. Simulations of the closed-loop reconfigurable system show that the approach produces a control design which can accommodate such failures with relative ease. The technique can be applied to many other problems including sensor failure accommodation, mode switching control laws and super agility.

Computer Optimization of Biodegradable Nanoparticles Fabricated by Dispersion Polymerization.

PubMed

Akala, Emmanuel O; Adesina, Simeon; Ogunwuyi, Oluwaseun

2015-12-22

Quality by design (QbD) in the pharmaceutical industry involves designing and developing drug formulations and manufacturing processes which ensure predefined drug product specifications. QbD helps to understand how process and formulation variables affect product characteristics and subsequent optimization of these variables vis-à-vis final specifications. Statistical design of experiments (DoE) identifies important parameters in a pharmaceutical dosage form design followed by optimizing the parameters with respect to certain specifications. DoE establishes in mathematical form the relationships between critical process parameters together with critical material attributes and critical quality attributes. We focused on the fabrication of biodegradable nanoparticles by dispersion polymerization. Aided by a statistical software, d-optimal mixture design was used to vary the components (crosslinker, initiator, stabilizer, and macromonomers) to obtain twenty nanoparticle formulations (PLLA-based nanoparticles) and thirty formulations (poly-ɛ-caprolactone-based nanoparticles). Scheffe polynomial models were generated to predict particle size (nm), zeta potential, and yield (%) as functions of the composition of the formulations. Simultaneous optimizations were carried out on the response variables. Solutions were returned from simultaneous optimization of the response variables for component combinations to (1) minimize nanoparticle size; (2) maximize the surface negative zeta potential; and (3) maximize percent yield to make the nanoparticle fabrication an economic proposition.

Mixed finite-element formulations in piezoelectricity and flexoelectricity

PubMed Central

2016-01-01

Flexoelectricity, the linear coupling of strain gradient and electric polarization, is inherently a size-dependent phenomenon. The energy storage function for a flexoelectric material depends not only on polarization and strain, but also strain-gradient. Thus, conventional finite-element methods formulated solely on displacement are inadequate to treat flexoelectric solids since gradients raise the order of the governing differential equations. Here, we introduce a computational framework based on a mixed formulation developed previously by one of the present authors and a colleague. This formulation uses displacement and displacement-gradient as separate variables which are constrained in a ‘weighted integral sense’ to enforce their known relation. We derive a variational formulation for boundary-value problems for piezo- and/or flexoelectric solids. We validate this computational framework against available exact solutions. Our new computational method is applied to more complex problems, including a plate with an elliptical hole, stationary cracks, as well as tension and shear of solids with a repeating unit cell. Our results address several issues of theoretical interest, generate predictions of experimental merit and reveal interesting flexoelectric phenomena with potential for application. PMID:27436967

Mixed finite-element formulations in piezoelectricity and flexoelectricity.

PubMed

Mao, Sheng; Purohit, Prashant K; Aravas, Nikolaos

2016-06-01

Flexoelectricity, the linear coupling of strain gradient and electric polarization, is inherently a size-dependent phenomenon. The energy storage function for a flexoelectric material depends not only on polarization and strain, but also strain-gradient. Thus, conventional finite-element methods formulated solely on displacement are inadequate to treat flexoelectric solids since gradients raise the order of the governing differential equations. Here, we introduce a computational framework based on a mixed formulation developed previously by one of the present authors and a colleague. This formulation uses displacement and displacement-gradient as separate variables which are constrained in a 'weighted integral sense' to enforce their known relation. We derive a variational formulation for boundary-value problems for piezo- and/or flexoelectric solids. We validate this computational framework against available exact solutions. Our new computational method is applied to more complex problems, including a plate with an elliptical hole, stationary cracks, as well as tension and shear of solids with a repeating unit cell. Our results address several issues of theoretical interest, generate predictions of experimental merit and reveal interesting flexoelectric phenomena with potential for application.

Optimized zein nanospheres for improved oral bioavailability of atorvastatin

PubMed Central

Hashem, Fahima M; Al-Sawahli, Majid M; Nasr, Mohamed; Ahmed, Osama AA

2015-01-01

Background This work focuses on the development of atorvastatin utilizing zein, a natural, safe, and biocompatible polymer, as a nanosized formulation in order to overcome the poor oral bioavailability (12%) of the drug. Methods Twelve experimental runs of atorvastatin–zein nanosphere formula were formulated by a liquid–liquid phase separation method according to custom fractional factorial design to optimize the formulation variables. The factors studied were: weight % of zein to atorvastatin (X1), pH (X2), and stirring time (X3). Levels for each formulation variable were designed. The selected dependent variables were: mean particle size (Y1), zeta potential (Y2), drug loading efficiency (Y3), drug encapsulation efficiency (Y4), and yield (Y5). The optimized formulation was assayed for compatibility using an X-ray diffraction assay. In vitro diffusion of the optimized formulation was carried out. A pharmacokinetic study was also done to compare the plasma profile of the atorvastatin–zein nanosphere formulation versus atorvastatin oral suspension and the commercially available tablet. Results The optimized atorvastatin–zein formulation had a mean particle size of 183 nm, a loading efficiency of 14.86%, and an encapsulation efficiency of 29.71%. The in vitro dissolution assay displayed an initial burst effect, with a cumulative amount of atorvastatin released of 41.76% and 82.3% after 12 and 48 hours, respectively. In Wistar albino rats, the bioavailability of atorvastatin from the optimized atorvastatin–zein formulation was 3-fold greater than that from the atorvastatin suspension and the commercially available tablet. Conclusion The atorvastatin–zein nanosphere formulation improved the oral delivery and pharmacokinetic profile of atorvastatin by enhancing its oral bioavailability. PMID:26150716

Identification of formulation and manufacturing variables that influence in vitro dissolution and in vivo bioavailability of propranolol hydrochloride tablets.

PubMed

Eddington, N D; Ashraf, M; Augsburger, L L; Leslie, J L; Fossler, M J; Lesko, L J; Shah, V P; Rekhi, G S

1998-11-01

The purpose of this study was to evaluate the effect of formulation and processing changes on the dissolution and bioavailability of propranolol hydrochloride tablets. Directly compressed blends of 6 kg (20,000 units) were prepared by mixing in a 16-qt V blender and tablets were compressed on an instrumented Manesty D3B tablet press. A half-factorial (2(5-1), Resolution V) design was used to study the following variables: filler ratio (lactose/dicalcium phosphate), sodium starch glycolate level, magnesium stearate level, lubricant blend time, and compression force. The levels and ranges of the excipients and processing changes studied represented level 2 or greater changes as indicated by the Scale-up and Post Approval Changes (SUPAC-IR) Guidance. Changes in filler ratio, disintegrant level, and compression force were significant in affecting percent drug released (Q) in 5 min (Q5) and Q10. However, changes in magnesium stearate level and lubricant blend time did not influence Q5 and Q10. Hardness was found to be affected by changes in all of the variables studied. Some interaction effects between the variables studied were also found to be significant. To examine the impact of formulation and processing variables on in vivo absorption, three batches were selected for a bioavailability study based on their dissolution profiles. Thirteen subjects received four propranolol treatments (slow-, medium-, and fast-dissolving formulations and Inderal 80 mg) separated by 1 week washout according to a randomized crossover design. The formulations were found to be bioequivalent with respect to the log Cmax and log AUC0-infinity. The results of this study suggest that (i) bioavailability/bioequivalency studies may not be necessary for propranolol and perhaps other class 1 drugs after level 2 type changes, and (ii) in vitro dissolution tests may be used to show bioequivalence of propranolol formulations with processing or formulation changes within the specified level 2 ranges examined.

Formulation and characterization of alprazolam-loaded nanoliposomes: screening of process variables and optimizing characteristics using RSM.

PubMed

Hashemi, Seyed Hesamoddin; Montazer, Majid; Naghdi, Nasser; Toliyat, Tayebeh

2018-02-01

This research study aimed to develop a novel sustained release formulation of alprazolam that can also be used for transdermal delivery. This was carried out, for the first time, through encapsulation of alprazolam in nanoliposomes using ethanol injection. In order to obtain the best formulation, four process variables, including the solvent/nonsolvent volume ratio, phospholipid concentration, alprazolam concentration, and cholesterol content were considered as key factors. Response surface methodology (RSM) and a central composite design (CCD) model were used to investigate the effect of these factors on vesicle size (VS) and encapsulation efficiency (EE) as the major properties of nanoliposomes. Experimental data were statistically analyzed, and two significant quadratic models were developed to test the VS and EE responses. The findings indicate that alprazolam and phospholipid concentrations have a significant effect on the mean VS. However, EE was significantly affected by both the alprazolam and phospholipid concentrations and the cholesterol content. The optimized formulation for preparation of alprazolam-loaded nanoliposomes with appropriate VS and EE was suggested. Small unilamellar vesicles (SUVs), ranging in size from 50 to 100 nm were clearly observed in the transmission electron microscopy (TEM) images, which is appropriate for transdermal delivery of alprazolam. The study of the prepared nanoliposomes over 28 days at 4 °C confirmed the stability of the formulations containing cholesterol. The results of an in vitro release study of alprazolam-loaded nanoliposomes in phosphate buffered saline (PBS), pH 7.4 for 24 h at 37 °C using dialysis, indicated the sustained release of alprazolam due to encapsulation.

Reciprocity theory of homogeneous reactions

NASA Astrophysics Data System (ADS)

Agbormbai, Adolf A.

1990-03-01

The reciprocity formalism is applied to the homogeneous gaseous reactions in which the structure of the participating molecules changes upon collision with one another, resulting in a change in the composition of the gas. The approach is applied to various classes of dissociation, recombination, rearrangement, ionizing, and photochemical reactions. It is shown that for the principle of reciprocity to be satisfied it is necessary that all chemical reactions exist in complementary pairs which consist of the forward and backward reactions. The backward reaction may be described by either the reverse or inverse process. The forward and backward processes must satisfy the same reciprocity equation. Because the number of dynamical variables is usually unbalanced on both sides of a chemical equation, it is necessary that this balance be established by including as many of the dynamical variables as needed before the reciprocity equation can be formulated. Statistical transformation models of the reactions are formulated. The models are classified under the titles free exchange, restricted exchange and simplified restricted exchange. The special equations for the forward and backward processes are obtained. The models are consistent with the H theorem and Le Chatelier's principle. The models are also formulated in the context of the direct simulation Monte Carlo method.

The mechanical and chemical equations of motion of muscle contraction

NASA Astrophysics Data System (ADS)

Shiner, J. S.; Sieniutycz, Stanislaw

1997-11-01

Up to now no formulation of muscle contraction has provided both the chemical kinetic equations for the reactions responsible for the contraction and the mechanical equation of motion for the muscle. This has most likely been due to the lack of general formalisms for nonlinear systems with chemical-nonchemical coupling valid under the far from equilibrium conditions under which muscle operates physiologically. We have recently developed such formalisms and apply them here to the formulation of muscle contraction to obtain both the chemical and the mechanical equations. The standard formulation up to now has yielded only the dynamic equations for the chemical variables and has considered these to be functions of both time and an appropriate mechanical variable. The macroscopically observable quantities were then obtained by averaging over the mechanical variable. When attempting to derive the dynamics equations for both the chemistry and mechanics this choice of variables leads to conflicting results for the mechanical equation of motion when two different general formalisms are applied. The conflict can be resolved by choosing the variables such that both the chemical variables and the mechanical variables are considered to be functions of time alone. This adds one equation to the set of differential equations to be solved but is actually a simplification of the problem, since these equations are ordinary differential equations, not the partial differential equations of the now standard formulation, and since in this choice of variables the variables themselves are the macroscopic observables the procedure of averaging over the mechanical variable is eliminated. Furthermore, the parameters occurring in the equations at this level of description should be accessible to direct experimental determination.

A spray flamelet/progress variable approach combined with a transported joint PDF model for turbulent spray flames

NASA Astrophysics Data System (ADS)

Hu, Yong; Olguin, Hernan; Gutheil, Eva

2017-05-01

A spray flamelet/progress variable approach is developed for use in spray combustion with partly pre-vaporised liquid fuel, where a laminar spray flamelet library accounts for evaporation within the laminar flame structures. For this purpose, the standard spray flamelet formulation for pure evaporating liquid fuel and oxidiser is extended by a chemical reaction progress variable in both the turbulent spray flame model and the laminar spray flame structures, in order to account for the effect of pre-vaporised liquid fuel for instance through use of a pilot flame. This new approach is combined with a transported joint probability density function (PDF) method for the simulation of a turbulent piloted ethanol/air spray flame, and the extension requires the formulation of a joint three-variate PDF depending on the gas phase mixture fraction, the chemical reaction progress variable, and gas enthalpy. The molecular mixing is modelled with the extended interaction-by-exchange-with-the-mean (IEM) model, where source terms account for spray evaporation and heat exchange due to evaporation as well as the chemical reaction rate for the chemical reaction progress variable. This is the first formulation using a spray flamelet model considering both evaporation and partly pre-vaporised liquid fuel within the laminar spray flamelets. Results with this new formulation show good agreement with the experimental data provided by A.R. Masri, Sydney, Australia. The analysis of the Lagrangian statistics of the gas temperature and the OH mass fraction indicates that partially premixed combustion prevails near the nozzle exit of the spray, whereas further downstream, the non-premixed flame is promoted towards the inner rich-side of the spray jet since the pilot flame heats up the premixed inner spray zone. In summary, the simulation with the new formulation considering the reaction progress variable shows good performance, greatly improving the standard formulation, and it provides new insight into the local structure of this complex spray flame.

State variable modeling of the integrated engine and aircraft dynamics

NASA Astrophysics Data System (ADS)

Rotaru, Constantin; Sprinţu, Iuliana

2014-12-01

This study explores the dynamic characteristics of the combined aircraft-engine system, based on the general theory of the state variables for linear and nonlinear systems, with details leading first to the separate formulation of the longitudinal and the lateral directional state variable models, followed by the merging of the aircraft and engine models into a single state variable model. The linearized equations were expressed in a matrix form and the engine dynamics was included in terms of variation of thrust following a deflection of the throttle. The linear model of the shaft dynamics for a two-spool jet engine was derived by extending the one-spool model. The results include the discussion of the thrust effect upon the aircraft response when the thrust force associated with the engine has a sizable moment arm with respect to the aircraft center of gravity for creating a compensating moment.

Application of hydroxyapatite nanoparticles in development of an enhanced formulation for delivering sustained release of triamcinolone acetonide

PubMed Central

Koocheki, Saeid; Madaeni, Sayed Siavash; Niroomandi, Parisa

2011-01-01

We report an analysis of in vitro and in vivo drug release from an in situ formulation consisting of triamcinolone acetonide (TR) and poly(d,l-lactide-co-glycolide) (PLGA) and the additives glycofurol (GL) and hydroxyapatite nanoparticles (HA). We found that these additives enhanced drug release rate. We used the Taguchi method to predict optimum formulation variables to minimize the initial burst. This method decreased the burst rate from 8% to 1.3%. PLGA-HA acted as a strong buffer, thereby preventing tissue inflammation at the injection site caused by the acidic degradation products of PLGA. Characterization of the optimized formulation by a variety of techniques, including scanning electron microscopy, X-ray diffraction, differential scanning calorimetry, and Fourier transform near infrared spectroscopy, revealed that the crystalline structure of TR was converted to an amorphous form. Therefore, this hydrophobic agent can serve as an additive to modify drug release rates. Data generated by in vitro and in vivo experiments were in good agreement. PMID:21589650

A defect stream function, law of the wall/wake method for compressible turbulent boundary layers

NASA Technical Reports Server (NTRS)

Barnwell, Richard W.; Dejarnette, Fred R.; Wahls, Richard A.

1989-01-01

The application of the defect stream function to the solution of the two-dimensional, compressible boundary layer is examined. A law of the wall/law of the wake formulation for the inner part of the boundary layer is presented which greatly simplifies the computational task near the wall and eliminates the need for an eddy viscosity model in this region. The eddy viscosity model in the outer region is arbitrary. The modified Crocco temperature-velocity relationship is used as a simplification of the differential energy equation. Formulations for both equilibrium and nonequilibrium boundary layers are presented including a constrained zero-order form which significantly reduces the computational workload while retaining the significant physics of the flow. A formulation for primitive variables is also presented. Results are given for the constrained zero-order and second-order equilibrium formulations and are compared with experimental data. A compressible wake function valid near the wall has been developed from the present results.

VCE testbed program planning and definition study

NASA Technical Reports Server (NTRS)

Westmoreland, J. S.; Godston, J.

1978-01-01

The flight definition of the Variable Stream Control Engine (VSCE) was updated to reflect design improvements in the two key components: (1) the low emissions duct burner, and (2) the coannular exhaust nozzle. The testbed design was defined and plans for the overall program were formulated. The effect of these improvements was evaluated for performance, emissions, noise, weight, and length. For experimental large scale testing of the duct burner and coannular nozzle, a design definition of the VCE testbed configuration was made. This included selecting the core engine, determining instrumentation requirements, and selecting the test facilities, in addition to defining control system and assembly requirements. Plans for a comprehensive test program to demonstrate the duct burner and nozzle technologies were formulated. The plans include both aeroacoustic and emissions testing.

Latent structure modeling underlying theophylline tablet formulations using a Bayesian network based on a self-organizing map clustering.

PubMed

Yasuda, Akihito; Onuki, Yoshinori; Obata, Yasuko; Takayama, Kozo

2015-01-01

The "quality by design" concept in pharmaceutical formulation development requires the establishment of a science-based rationale and design space. In this article, we integrate thin-plate spline (TPS) interpolation, Kohonen's self-organizing map (SOM) and a Bayesian network (BN) to visualize the latent structure underlying causal factors and pharmaceutical responses. As a model pharmaceutical product, theophylline tablets were prepared using a standard formulation. We measured the tensile strength and disintegration time as response variables and the compressibility, cohesion and dispersibility of the pretableting blend as latent variables. We predicted these variables quantitatively using nonlinear TPS, generated a large amount of data on pretableting blends and tablets and clustered these data into several clusters using a SOM. Our results show that we are able to predict the experimental values of the latent and response variables with a high degree of accuracy and are able to classify the tablet data into several distinct clusters. In addition, to visualize the latent structure between the causal and latent factors and the response variables, we applied a BN method to the SOM clustering results. We found that despite having inserted latent variables between the causal factors and response variables, their relation is equivalent to the results for the SOM clustering, and thus we are able to explain the underlying latent structure. Consequently, this technique provides a better understanding of the relationships between causal factors and pharmaceutical responses in theophylline tablet formulation.

Influence of cellulose derivative and ethylene glycol on optimization of lornoxicam transdermal formulation.

PubMed

Shahzad, Yasser; Khan, Qalandar; Hussain, Talib; Shah, Syed Nisar Hussain

2013-10-01

Lornoxicam containing topically applied lotions were formulated and optimized with the aim to deliver it transdermally. The formulated lotions were evaluated for pH, viscosity and in vitro permeation studies through silicone membrane using Franz diffusion cells. Data were fitted to linear, quadratic and cubic models and best fit model was selected to investigate the influence of variables, namely hydroxypropyl methylcellulose (HPMC) and ethylene glycol (EG) on permeation of lornoxicam from topically applied lotion formulations. The best fit quadratic model revealed that low level of HPMC and intermediate level of EG in the formulation was optimum for enhancing the drug flux across silicone membrane. FT-IR analysis confirmed absence of drug-polymer interactions. Selected optimized lotion formulation was then subjected to accelerated stability testing, sensatory perception testing and in vitro permeation across rabbit skin. The drug flux from the optimized lotion across rabbit skin was significantly better that that from the control formulation. Furthermore, sensatory perception test rated a higher acceptability while lotion was stable over stability testing period. Therefore, use of Box-Wilson statistical design successfully elaborated the influence of formulation variables on permeation of lornoxicam form topical formulations, thus, helped in optimization of the lotion formulation. Copyright © 2013 Elsevier B.V. All rights reserved.

Solubility and bioavailability improvement of pazopanib hydrochloride.

PubMed

Herbrink, Maikel; Groenland, Stefanie L; Huitema, Alwin D R; Schellens, Jan H M; Beijnen, Jos H; Steeghs, Neeltje; Nuijen, Bastiaan

2018-06-10

The anti-cancer drug pazopanib hydrochloride (PZH) has a very low aqueous solubility and a variable oral bioavailability. A new pharmaceutical formulation with an improved solubility may enhance the bioavailability and reduce the variability. A broad selection of polymer excipients was tested for their compatibility and solubilizing properties by conventional microscopic, thermal and spectrometric techniques. A wet milling and mixing technique was used to produce homogenous powder mixtures. The dissolution properties of the formulation were tested by a pH-switch dissolution model. The final formulation was tested in vivo in cancer patient following a dose escalation design. Of the tested mixture formulations, the one containing the co-block polymer Soluplus® in a 8:1 ratio with PZH performed best in terms of in vitro dissolution properties. The in vivo results indicated that 300 mg of the developed formulation yields similar exposure and a lower variability (379 μg/mL∗h (36.7% CV)) than previously reported values for the standard PZH formulation (Votrient®) at the approved dose of 800 mg. Furthermore, the expected plasma-C through levels (27.2 μg/mL) exceeds the defined therapeutic efficacy threshold of 20 μg/mL. Copyright © 2018 Elsevier B.V. All rights reserved.

Floating drug delivery systems: a review.

PubMed

Arora, Shweta; Ali, Javed; Ahuja, Alka; Khar, Roop K; Baboota, Sanjula

2005-10-19

The purpose of writing this review on floating drug delivery systems (FDDS) was to compile the recent literature with special focus on the principal mechanism of floatation to achieve gastric retention. The recent developments of FDDS including the physiological and formulation variables affecting gastric retention, approaches to design single-unit and multiple-unit floating systems, and their classification and formulation aspects are covered in detail. This review also summarizes the in vitro techniques, in vivo studies to evaluate the performance and application of floating systems, and applications of these systems. These systems are useful to several problems encountered during the development of a pharmaceutical dosage form.

Melamine-modified urea formaldehyde resin for bonding particleboards

Treesearch

Chung-Yun Hse; Feng Fu; Hui Pan

2008-01-01

For the development of a cost-effective melamine-modified urea formaldehyde resin (MUF), the study evaluated the effects of reaction pH and melamine content on resin properties and bond performance of the MUF resin adhesive systems. Eight resins, each with three replicates, were prepared in a factorial experiment that included two formulation variables: two reaction...

Bond quality of phenol-based adhesives containing liquefied creosote-treated wood

Treesearch

Chung-Yun Hse; Feng Fu; Hui Pan

2009-01-01

Liquefaction of spent creosote-treated wood was studied to determine the technological practicability of its application in converting treated wood waste into resin adhesives. A total of 144 plywood panels were fabricated with experimental variables included 2 phenol to wood (P/W) ratios in liquefaction, 6 resin formulations (3 formaldehyde/liquefied wood (F/...

Culture, cultural factors and psychiatric diagnosis: review and projections.

PubMed

Alarcón, Renato D

2009-10-01

This paper aims to provide conceptual justifications for the inclusion of culture and cultural factors in psychiatric diagnosis, and logistic suggestions as to the content and use of this approach. A discussion of the scope and limitations of current diagnostic practice, criticisms from different quarters, and the role and relevance of culture in the diagnostic encounter, precede the examination of advantages and disadvantages of the approach. The cultural content of psychiatric diagnosis should include the main, well-recognized cultural variables, adequate family data, explanatory models, and strengths and weaknesses of every individual patient. The practical aspects include the acceptance of "cultural discordances" as a component of an updated definition of mental disorder, and the use of a refurbished cultural formulation. Clinical "telescoping" strategies to obtain relevant cultural data during the diagnostic interview, and areas of future research (including field trials on the cultural formulation and on "culture bound syndromes"), are outlined.

Identification and stochastic control of helicopter dynamic modes

NASA Technical Reports Server (NTRS)

Molusis, J. A.; Bar-Shalom, Y.

1983-01-01

A general treatment of parameter identification and stochastic control for use on helicopter dynamic systems is presented. Rotor dynamic models, including specific applications to rotor blade flapping and the helicopter ground resonance problem are emphasized. Dynamic systems which are governed by periodic coefficients as well as constant coefficient models are addressed. The dynamic systems are modeled by linear state variable equations which are used in the identification and stochastic control formulation. The pure identification problem as well as the stochastic control problem which includes combined identification and control for dynamic systems is addressed. The stochastic control problem includes the effect of parameter uncertainty on the solution and the concept of learning and how this is affected by the control's duel effect. The identification formulation requires algorithms suitable for on line use and thus recursive identification algorithms are considered. The applications presented use the recursive extended kalman filter for parameter identification which has excellent convergence for systems without process noise.

Testing high SPF sunscreens: a demonstration of the accuracy and reproducibility of the results of testing high SPF formulations by two methods and at different testing sites.

PubMed

Agin, Patricia Poh; Edmonds, Susan H

2002-08-01

The goals of this study were (i) to demonstrate that existing and widely used sun protection factor (SPF) test methodologies can produce accurate and reproducible results for high SPF formulations and (ii) to provide data on the number of test-subjects needed, the variability of the data, and the appropriate exposure increments needed for testing high SPF formulations. Three high SPF formulations were tested, according to the Food and Drug Administration's (FDA) 1993 tentative final monograph (TFM) 'very water resistant' test method and/or the 1978 proposed monograph 'waterproof' test method, within one laboratory. A fourth high SPF formulation was tested at four independent SPF testing laboratories, using the 1978 waterproof SPF test method. All laboratories utilized xenon arc solar simulators. The data illustrate that the testing conducted within one laboratory, following either the 1978 proposed or the 1993 TFM SPF test method, was able to reproducibly determine the SPFs of the formulations tested, using either the statistical analysis method in the proposed monograph or the statistical method described in the TFM. When one formulation was tested at four different laboratories, the anticipated variation in the data owing to the equipment and other operational differences was minimized through the use of the statistical method described in the 1993 monograph. The data illustrate that either the 1978 proposed monograph SPF test method or the 1993 TFM SPF test method can provide accurate and reproducible results for high SPF formulations. Further, these results can be achieved with panels of 20-25 subjects with an acceptable level of variability. Utilization of the statistical controls from the 1993 sunscreen monograph can help to minimize lab-to-lab variability for well-formulated products.

A numerical study of the 2- and 3-dimensional unsteady Navier-Stokes equations in velocity-vorticity variables using compact difference schemes

NASA Technical Reports Server (NTRS)

Gatski, T. B.; Grosch, C. E.

1984-01-01

A compact finite-difference approximation to the unsteady Navier-Stokes equations in velocity-vorticity variables is used to numerically simulate a number of flows. These include two-dimensional laminar flow of a vortex evolving over a flat plate with an embedded cavity, the unsteady flow over an elliptic cylinder, and aspects of the transient dynamics of the flow over a rearward facing step. The methodology required to extend the two-dimensional formulation to three-dimensions is presented.

Variable Cycle Engine Technology Program Planning and Definition Study

NASA Technical Reports Server (NTRS)

Westmoreland, J. S.; Stern, A. M.

1978-01-01

The variable stream control engine, VSCE-502B, was selected as the base engine, with the inverted flow engine concept selected as a backup. Critical component technologies were identified, and technology programs were formulated. Several engine configurations were defined on a preliminary basis to serve as demonstration vehicles for the various technologies. The different configurations present compromises in cost, technical risk, and technology return. Plans for possible variably cycle engine technology programs were formulated by synthesizing the technology requirements with the different demonstrator configurations.

A comprehensive linear programming tool to optimize formulations of ready-to-use therapeutic foods: an application to Ethiopia.

PubMed

Ryan, Kelsey N; Adams, Katherine P; Vosti, Stephen A; Ordiz, M Isabel; Cimo, Elizabeth D; Manary, Mark J

2014-12-01

Ready-to-use therapeutic food (RUTF) is the standard of care for children suffering from noncomplicated severe acute malnutrition (SAM). The objective was to develop a comprehensive linear programming (LP) tool to create novel RUTF formulations for Ethiopia. A systematic approach that surveyed international and national crop and animal food databases was used to create a global and local candidate ingredient database. The database included information about each ingredient regarding nutrient composition, ingredient category, regional availability, and food safety, processing, and price. An LP tool was then designed to compose novel RUTF formulations. For the example case of Ethiopia, the objective was to minimize the ingredient cost of RUTF; the decision variables were ingredient weights and the extent of use of locally available ingredients, and the constraints were nutritional and product-quality related. Of the new RUTF formulations found by the LP tool for Ethiopia, 32 were predicted to be feasible for creating a paste, and these were prepared in the laboratory. Palatable final formulations contained a variety of ingredients, including fish, different dairy powders, and various seeds, grains, and legumes. Nearly all of the macronutrient values calculated by the LP tool differed by <10% from results produced by laboratory analyses, but the LP tool consistently underestimated total energy. The LP tool can be used to develop new RUTF formulations that make more use of locally available ingredients. This tool has the potential to lead to production of a variety of low-cost RUTF formulations that meet international standards and thereby potentially allow more children to be treated for SAM. © 2014 American Society for Nutrition.

A Damage Model for the Simulation of Delamination in Advanced Composites under Variable-Mode Loading

NASA Technical Reports Server (NTRS)

Turon, A.; Camanho, P. P.; Costa, J.; Davila, C. G.

2006-01-01

A thermodynamically consistent damage model is proposed for the simulation of progressive delamination in composite materials under variable-mode ratio. The model is formulated in the context of Damage Mechanics. A novel constitutive equation is developed to model the initiation and propagation of delamination. A delamination initiation criterion is proposed to assure that the formulation can account for changes in the loading mode in a thermodynamically consistent way. The formulation accounts for crack closure effects to avoid interfacial penetration of two adjacent layers after complete decohesion. The model is implemented in a finite element formulation, and the numerical predictions are compared with experimental results obtained in both composite test specimens and structural components.

Identification of critical formulation and processing variables for metoprolol tartrate extended-release (ER) matrix tablets.

PubMed

Rekhi, G S; Nellore, R V; Hussain, A S; Tillman, L G; Malinowski, H J; Augsburger, L L

1999-06-02

The objective of this study, was to examine the influence of critical formulation and processing variables as described in the AAPS/FDA Workshop II report on scale-up of oral extended-release dosage forms, using a hydrophilic polymer hydroxypropyl methylcellulose (Methocel K100LV). A face-centered central composite design (26 runs+3 center points) was selected and the variables studied were: filler ratio (lactose:dicalcium phosphate (50:50)), polymer level (15/32.5/50%), magnesium stearate level (1/1.5/2%), lubricant blend time (2/6/10 min) and compression force (400/600/800 kg). Granulations (1.5 kg, 3000 units) were manufactured using a fluid-bed process, lubricated and tablets (100 mg metoprolol tartrate) were compressed on an instrumented Manesty D3B rotary tablet press. Dissolution tests were performed using USP apparatus 2, at 50 rpm in 900 ml phosphate buffer (pH 6.8). Responses studied included percent drug released at Q1 (1 h), Q4, Q6, Q12. Analysis of variance indicated that change in polymer level was the most significant factor affecting drug release. Increase in dicalcium phosphate level and compression force were found to affect the percent released at the later dissolution time points. Some interaction effects between the variables studied were also found to be statistically significant. The drug release mechanism was predominantly found to be Fickian diffusion controlled (n=0.46-0.59). Response surface plots and regression models were developed which adequately described the experimental space. Three formulations having slow-, medium- and fast-releasing dissolution profiles were identified for a future bioavailability/bioequivalency study. The results of this study provided the framework for further work involving both in vivo studies and scale-up.

Adaptable structural synthesis using advanced analysis and optimization coupled by a computer operating system

NASA Technical Reports Server (NTRS)

Sobieszczanski-Sobieski, J.; Bhat, R. B.

1979-01-01

A finite element program is linked with a general purpose optimization program in a 'programing system' which includes user supplied codes that contain problem dependent formulations of the design variables, objective function and constraints. The result is a system adaptable to a wide spectrum of structural optimization problems. In a sample of numerical examples, the design variables are the cross-sectional dimensions and the parameters of overall shape geometry, constraints are applied to stresses, displacements, buckling and vibration characteristics, and structural mass is the objective function. Thin-walled, built-up structures and frameworks are included in the sample. Details of the system organization and characteristics of the component programs are given.

Atorvastatin calcium encapsulated eudragit nanoparticles with enhanced oral bioavailability, safety and efficacy profile.

PubMed

Kumar, Nagendra; Chaurasia, Sundeep; Patel, Ravi R; Khan, Gayasuddin; Kumar, Vikas; Mishra, Brahmeshwar

2017-03-01

Atorvastatin calcium (ATR), a second generation statin drug, was encapsulated in eudragit RSPO-based polymeric nanoparticles. The effect of independent variables (polymer content, stabilizer concentration, volume of chloroform and homogenization speed) on response variables (mean diameter particle size and entrapment efficiency) were investigated by employing central composite experimental design. All the independent variables were found to be significant for determining the response variables. Solid-state characterization study indicated the absence of physicochemical interaction between drug and polymer in formulation. Morphological study exhibited homogenous spherical shape of formulated nanoparticles. In vitro release study in phosphate buffer (pH 7.4) demonstrated sustained release profile over 24 h. Pharmacokinetic study in Charles Foster rats showed significant enhancement in oral bioavailability as compared to pure drug suspension. Efficacy study (lipid profile and blood glucose level) significantly justified the effectiveness of formulation having 50% less dose of ATR as compared to pure drug suspension. The effectiveness of formulation was further justified with an improved plasma safety profile of treated rats. Hence, ATR encapsulated eudragit RSPO nanoparticles can serve as potential drug delivery approach to enhance drug bioavailability, efficacy and safety profiles to alter existing marketed drug products.

Comparison of neurofuzzy logic and decision trees in discovering knowledge from experimental data of an immediate release tablet formulation.

PubMed

Shao, Q; Rowe, R C; York, P

2007-06-01

Understanding of the cause-effect relationships between formulation ingredients, process conditions and product properties is essential for developing a quality product. However, the formulation knowledge is often hidden in experimental data and not easily interpretable. This study compares neurofuzzy logic and decision tree approaches in discovering hidden knowledge from an immediate release tablet formulation database relating formulation ingredients (silica aerogel, magnesium stearate, microcrystalline cellulose and sodium carboxymethylcellulose) and process variables (dwell time and compression force) to tablet properties (tensile strength, disintegration time, friability, capping and drug dissolution at various time intervals). Both approaches successfully generated useful knowledge in the form of either "if then" rules or decision trees. Although different strategies are employed by the two approaches in generating rules/trees, similar knowledge was discovered in most cases. However, as decision trees are not able to deal with continuous dependent variables, data discretisation procedures are generally required.

Comparative evaluation of propofol in nanoemulsion with solutol and soy lecithin for general anesthesia.

PubMed

Rittes, José Carlos; Cagno, Guilherme; Perez, Marcelo Vaz; Mathias, Ligia Andrade da Silva Telles

2016-01-01

The vehicle for propofol in 1 and 2% solutions is soybean oil emulsion 10%, which may cause pain on injection, instability of the solution and bacterial contamination. Formulations have been proposed aiming to change the vehicle and reduce these adverse reactions. To compare the incidence of pain caused by the injection of propofol, with a hypothesis of reduction associated with nanoemulsion and the occurrence of local and systemic adverse effects with both formulations. After approval by the CEP, patients undergoing gynecological procedures were included in this prospective study: control (n=25) and nanoemulsion (n=25) groups. Heart rate, noninvasive blood pressure and peripheral oxygen saturation were monitored. Demographics and physical condition were analyzed; surgical time and total volume used of propofol; local or systemic adverse effects; changes in variables monitored. A value of p<0.05 was considered significant. There was no difference between groups regarding demographic data, surgical times, total volume of propofol used, arm withdrawal, pain during injection and variables monitored. There was a statistically significant difference in pain intensity at the time of induction of anesthesia, with less pain intensity in the nanoemulsion group. Both lipid and nanoemulsion formulations of propofol elicited pain on intravenous injection; however, the nanoemulsion solution elicited a less intense pain. Lipid and nanoemulsion propofol formulations showed neither hemodynamic changes nor adverse effects of clinical relevance. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

Optimization of Primary Drying in Lyophilization during Early Phase Drug Development using a Definitive Screening Design with Formulation and Process Factors.

PubMed

Goldman, Johnathan M; More, Haresh T; Yee, Olga; Borgeson, Elizabeth; Remy, Brenda; Rowe, Jasmine; Sadineni, Vikram

2018-06-08

Development of optimal drug product lyophilization cycles is typically accomplished via multiple engineering runs to determine appropriate process parameters. These runs require significant time and product investments, which are especially costly during early phase development when the drug product formulation and lyophilization process are often defined simultaneously. Even small changes in the formulation may require a new set of engineering runs to define lyophilization process parameters. In order to overcome these development difficulties, an eight factor definitive screening design (DSD), including both formulation and process parameters, was executed on a fully human monoclonal antibody (mAb) drug product. The DSD enables evaluation of several interdependent factors to define critical parameters that affect primary drying time and product temperature. From these parameters, a lyophilization development model is defined where near optimal process parameters can be derived for many different drug product formulations. This concept is demonstrated on a mAb drug product where statistically predicted cycle responses agree well with those measured experimentally. This design of experiments (DoE) approach for early phase lyophilization cycle development offers a workflow that significantly decreases the development time of clinically and potentially commercially viable lyophilization cycles for a platform formulation that still has variable range of compositions. Copyright © 2018. Published by Elsevier Inc.

HIGH SHEAR GRANULATION PROCESS: ASSESSING IMPACT OF FORMULATION VARIABLES ON GRANULES AND TABLETS CHARACTERISTICS OF HIGH DRUG LOADING FORMULATION USING DESIGN OF EXPERIMENT METHODOLOGY.

PubMed

Fayed, Mohamed H; Abdel-Rahman, Sayed I; Alanazi, Fars K; Ahmed, Mahrous O; Tawfeek, Hesham M; Ali, Bahaa E

2017-03-01

High shear wet granulation is a significant component procedure in the pharmaceutical industry. The objective of the study was to investigate the influence of two independent formulation variables; polyvinypyrrolidone (PVP) as a binder (X,) and croscarmellose sodium (CCS) as a disintegrant (X2) on the crit- ical quality attributes of acetaminophen granules and their corresponding tablets using design of experiment (DoE) approach. A two factor, three level (32) full factorial design has been applied; each variable was investi- gated at three levels to characterize their strength and interaction. The dried granules have been analyzed for their density, granule size and flowability. Additionally, the produced tablets have been investigated for: break- ing force, friability, disintegration time and t. of drug dissolution. The analysis of variance (ANOVA) showed that the two variables had a significant impact (p < 0.05) on granules and tablets characteristics, while only the binder concentration influenced the tablets friability. Furthermore, significant interactions (p < 0.05) between the two variables, for granules and tablets attributes, were also found. However, variables interaction showed minimal effect for granules flowability as well as tablets friability. Desirability function was carried out to opti- mize the variables under study to obtain product within the USP limit. It was found that the higher desirability (0.985) could be obtained at the medium level of PVP and low level of CCS. Ultimately, this study supplies the formulator with beneficial tools in selecting the proper level of binder and disintegrant to attain product with desired characteristics.

Documentation for the State Variables Package for the Groundwater-Management Process of MODFLOW-2005 (GWM-2005)

USGS Publications Warehouse

Ahlfeld, David P.; Barlow, Paul M.; Baker, Kristine M.

2011-01-01

Many groundwater-management problems are concerned with the control of one or more variables that reflect the state of a groundwater-flow system or a coupled groundwater/surface-water system. These system state variables include the distribution of heads within an aquifer, streamflow rates within a hydraulically connected stream, and flow rates into or out of aquifer storage. This report documents the new State Variables Package for the Groundwater-Management Process of MODFLOW-2005 (GWM-2005). The new package provides a means to explicitly represent heads, streamflows, and changes in aquifer storage as state variables in a GWM-2005 simulation. The availability of these state variables makes it possible to include system state in the objective function and enhances existing capabilities for constructing constraint sets for a groundwater-management formulation. The new package can be used to address groundwater-management problems such as the determination of withdrawal strategies that meet water-supply demands while simultaneously maximizing heads or streamflows, or minimizing changes in aquifer storage. Four sample problems are provided to demonstrate use of the new package for typical groundwater-management applications.

Efficient Trajectory Propagation for Orbit Determination Problems

NASA Technical Reports Server (NTRS)

Roa, Javier; Pelaez, Jesus

2015-01-01

Regularized formulations of orbital motion apply a series of techniques to improve the numerical integration of the orbit. Despite their advantages and potential applications little attention has been paid to the propagation of the partial derivatives of the corresponding set of elements or coordinates, required in many orbit-determination scenarios and optimization problems. This paper fills this gap by presenting the general procedure for integrating the state-transition matrix of the system together with the nominal trajectory using regularized formulations and different sets of elements. The main difficulty comes from introducing an independent variable different from time, because the solution needs to be synchronized. The correction of the time delay is treated from a generic perspective not focused on any particular formulation. The synchronization using time-elements is also discussed. Numerical examples include strongly-perturbed orbits in the Pluto system, motivated by the recent flyby of the New Horizons spacecraft, together with a geocentric flyby of the NEAR spacecraft.

Spray drying formulation of amorphous solid dispersions.

PubMed

Singh, Abhishek; Van den Mooter, Guy

2016-05-01

Spray drying is a well-established manufacturing technique which can be used to formulate amorphous solid dispersions (ASDs) which is an effective strategy to deliver poorly water soluble drugs (PWSDs). However, the inherently complex nature of the spray drying process coupled with specific characteristics of ASDs makes it an interesting area to explore. Numerous diverse factors interact in an inter-dependent manner to determine the final product properties. This review discusses the basic background of ASDs, various formulation and process variables influencing the critical quality attributes (CQAs) of the ASDs and aspects of downstream processing. Also various aspects of spray drying such as instrumentation, thermodynamics, drying kinetics, particle formation process and scale-up challenges are included. Recent advances in the spray-based drying techniques are mentioned along with some future avenues where major research thrust is needed. Copyright © 2015 Elsevier B.V. All rights reserved.

Flexible pavement overlay design procedures. Volume 1: Evaluation and modification of the design methods

NASA Astrophysics Data System (ADS)

Majidzadeh, K.; Ilves, G. J.

1981-08-01

A ready reference to design procedures for asphaltic concrete overlay of flexible pavements based on elastic layer theory is provided. The design procedures and the analytical techniques presented were formulated to predict the structural fatigue response of asphaltic concrete overlays for various design conditions, including geometrical and material properties, loading conditions and environmental variables.

Optimization of controlled release nanoparticle formulation of verapamil hydrochloride using artificial neural networks with genetic algorithm and response surface methodology.

PubMed

Li, Yongqiang; Abbaspour, Mohammadreza R; Grootendorst, Paul V; Rauth, Andrew M; Wu, Xiao Yu

2015-08-01

This study was performed to optimize the formulation of polymer-lipid hybrid nanoparticles (PLN) for the delivery of an ionic water-soluble drug, verapamil hydrochloride (VRP) and to investigate the roles of formulation factors. Modeling and optimization were conducted based on a spherical central composite design. Three formulation factors, i.e., weight ratio of drug to lipid (X1), and concentrations of Tween 80 (X2) and Pluronic F68 (X3), were chosen as independent variables. Drug loading efficiency (Y1) and mean particle size (Y2) of PLN were selected as dependent variables. The predictive performance of artificial neural networks (ANN) and the response surface methodology (RSM) were compared. As ANN was found to exhibit better recognition and generalization capability over RSM, multi-objective optimization of PLN was then conducted based upon the validated ANN models and continuous genetic algorithms (GA). The optimal PLN possess a high drug loading efficiency (92.4%, w/w) and a small mean particle size (∼100nm). The predicted response variables matched well with the observed results. The three formulation factors exhibited different effects on the properties of PLN. ANN in coordination with continuous GA represent an effective and efficient approach to optimize the PLN formulation of VRP with desired properties. Copyright © 2015 Elsevier B.V. All rights reserved.

Drought risk assessment under climate change is sensitive to methodological choices for the estimation of evaporative demand.

PubMed

Dewes, Candida F; Rangwala, Imtiaz; Barsugli, Joseph J; Hobbins, Michael T; Kumar, Sanjiv

2017-01-01

Several studies have projected increases in drought severity, extent and duration in many parts of the world under climate change. We examine sources of uncertainty arising from the methodological choices for the assessment of future drought risk in the continental US (CONUS). One such uncertainty is in the climate models' expression of evaporative demand (E0), which is not a direct climate model output but has been traditionally estimated using several different formulations. Here we analyze daily output from two CMIP5 GCMs to evaluate how differences in E0 formulation, treatment of meteorological driving data, choice of GCM, and standardization of time series influence the estimation of E0. These methodological choices yield different assessments of spatio-temporal variability in E0 and different trends in 21st century drought risk. First, we estimate E0 using three widely used E0 formulations: Penman-Monteith; Hargreaves-Samani; and Priestley-Taylor. Our analysis, which primarily focuses on the May-September warm-season period, shows that E0 climatology and its spatial pattern differ substantially between these three formulations. Overall, we find higher magnitudes of E0 and its interannual variability using Penman-Monteith, in particular for regions like the Great Plains and southwestern US where E0 is strongly influenced by variations in wind and relative humidity. When examining projected changes in E0 during the 21st century, there are also large differences among the three formulations, particularly the Penman-Monteith relative to the other two formulations. The 21st century E0 trends, particularly in percent change and standardized anomalies of E0, are found to be sensitive to the long-term mean value and the amplitude of interannual variability, i.e. if the magnitude of E0 and its interannual variability are relatively low for a particular E0 formulation, then the normalized or standardized 21st century trend based on that formulation is amplified relative to other formulations. This is the case for the use of Hargreaves-Samani and Priestley-Taylor, where future E0 trends are comparatively much larger than for Penman-Monteith. When comparing Penman-Monteith E0 responses between different choices of input variables related to wind speed, surface roughness, and net radiation, we found differences in E0 trends, although these choices had a much smaller influence on E0 trends than did the E0 formulation choices. These methodological choices and specific climate model selection, also have a large influence on the estimation of trends in standardized drought indices used for drought assessment operationally. We find that standardization tends to amplify divergences between the E0 trends calculated using different E0 formulations, because standardization is sensitive to both the climatology and amplitude of interannual variability of E0. For different methodological choices and GCM output considered in estimating E0, we examine potential sources of uncertainty in 21st century trends in the Standardized Precipitation Evapotranspiration Index (SPEI) and Evaporative Demand Drought Index (EDDI) over selected regions of the CONUS to demonstrate the practical implications of these methodological choices for the quantification of drought risk under climate change.

Challenges of Formulation of Strategic Plans in Secondary Schools in Kenya: A Case of Mombasa County and Its Environs

ERIC Educational Resources Information Center

Nyagah, Agnes S. M.

2015-01-01

The study is aimed at analyzing the factors that affect formulation of strategic plans in secondary schools in Mombasa County and its environs. The study looks at various variables namely leadership, training, resources allocation and education policy frameworks as the main challenges. The paper concludes that the above variables to a large extent…

Novel formulation of abiraterone acetate might allow significant dose reduction and eliminates substantial positive food effect.

PubMed

Solymosi, Tamás; Ötvös, Zsolt; Angi, Réka; Ordasi, Betti; Jordán, Tamás; Molnár, László; McDermott, John; Zann, Vanessa; Church, Ann; Mair, Stuart; Filipcsei, Genovéva; Heltovics, Gábor; Glavinas, Hristos

2017-10-01

Zytiga (abiraterone acetate, AA) is known to exhibit very low bioavailability and a significant positive food effect in men. The unfavorable pharmacokinetic properties are attributed to the inadequate and variable dissolution of the compound. Using a continuous flow precipitation technology, a novel AA formulation has been developed with improved solubility and dissolution characteristics. The current study was performed to evaluate the pharmacokinetics and safety of this novel formulation in healthy volunteers. The study was conducted in 11 healthy men aged 47-57 years. All subjects received 3 consecutive single doses of the novel formulation of AA (100 and 200 mg in the fasted state and 200 mg in the fed state). Data were compared with pharmacokinetic and safety data reported for 1000 mg Zytiga, the marketed drug. The novel formulation of AA allows rapid absorption of the compound with t max values within 1 hour. Based on AUC values, a ~250 mg dose of the novel formulation is predicted to give the same exposure as 1000 mg Zytiga in the fasted state. The significant positive food effect was also eliminated; actually, a slight, but statistically significant negative food effect was observed. Variability of exposure was significantly reduced when compared to Zytiga. AA administered in the novel formulation was well tolerated with no IMP-related safety AEs reported. The novel formulation might allow a 75% dose reduction with significant reduction of inter-individual variability. The negative food effect observed requires further investigations; however, elimination of the significant positive food effect could be adequate to negate the restriction of a food label.

A Three-Dimensional Finite-Element Model for Simulating Water Flow in Variably Saturated Porous Media

NASA Astrophysics Data System (ADS)

Huyakorn, Peter S.; Springer, Everett P.; Guvanasen, Varut; Wadsworth, Terry D.

1986-12-01

A three-dimensional finite-element model for simulating water flow in variably saturated porous media is presented. The model formulation is general and capable of accommodating complex boundary conditions associated with seepage faces and infiltration or evaporation on the soil surface. Included in this formulation is an improved Picard algorithm designed to cope with severely nonlinear soil moisture relations. The algorithm is formulated for both rectangular and triangular prism elements. The element matrices are evaluated using an "influence coefficient" technique that avoids costly numerical integration. Spatial discretization of a three-dimensional region is performed using a vertical slicing approach designed to accommodate complex geometry with irregular boundaries, layering, and/or lateral discontinuities. Matrix solution is achieved using a slice successive overrelaxation scheme that permits a fairly large number of nodal unknowns (on the order of several thousand) to be handled efficiently on small minicomputers. Six examples are presented to verify and demonstrate the utility of the proposed finite-element model. The first four examples concern one- and two-dimensional flow problems used as sample problems to benchmark the code. The remaining examples concern three-dimensional problems. These problems are used to illustrate the performance of the proposed algorithm in three-dimensional situations involving seepage faces and anisotropic soil media.

Pharmacokinetics of a Sustained-release Formulation of Meloxicam After Subcutaneous Administration to Hispaniolan Amazon Parrots (Amazona ventralis).

PubMed

Guzman, David Sanchez-Migallon; Court, Michael H; Zhu, Zhaohui; Summa, Noémie; Paul-Murphy, Joanne R

2017-09-01

Meloxicam has been shown to have a safe and favorable pharmacodynamic profile with individual variability in Hispaniolan Amazon parrots (Amazona ventralis). In the current study, we determined the pharmacokinetics of a sustained-release formulation of meloxicam after subcutaneous administration to Hispaniolan Amazon parrots. Twelve healthy adult parrots, 6 males and 6 females, were used in the study. Blood samples were collected before (time 0) and at 0.5, 1, 2, 6, 12, 24, 48, 72, 96, and 120 hours after a single dose of the sustained-release meloxicam formulation (3 mg/kg SC). Plasma meloxicam concentrations were measured by high-pressure liquid chromatography. Pharmacokinetic parameters were determined by noncompartmental analysis. Plasma concentrations reached a mean C max of 23.4 μg/mL (range, 14.7-46.0 μg/mL) at 1.8 hours (range, 0.5-6 hours), with a terminal half-life of 7.4 hours (range, 1.4-40.9 hours). Individual variation was noticeable, such that some parrots (4 of 12 birds) had very low plasma meloxicam concentrations, similar to the high variability reported in a previous pharmacokinetic study of the standard meloxicam formulation in the same group of birds. Two birds developed small self-resolving scabs at the injection site. On the basis of these results, the sustained-release meloxicam formulation could be administered every 12 to 96 hours in Hispaniolan Amazon parrots to manage pain. Because of these highly variable results, the use of this formulation in this species cannot be recommended until further pharmacokinetic, safety, and pharmacogenomic evaluations are performed to establish accurate dosing recommendations and to understand the high pharmacokinetic variability.

In vivo efficacy and bioavailability of lumefantrine: Evaluating the application of Pheroid technology.

PubMed

du Plessis, Lissinda H; Govender, Katya; Denti, Paolo; Wiesner, Lubbe

2015-11-01

The oral absorption of compounds with low aqueous solubility, such as lumefantrine, is typically limited by the dissolution rate in the gastro-intestinal tract, resulting in erratic absorption and highly variable bioavailability. In previous studies we reported on the ability of Pheroid vesicles to improve the bioavailability of poorly soluble drugs. In the present study a Pro-Pheroid formulation, a modification of the previous formulation, was applied to improve the solubility of lumefantrine after oral administration and compared to lumefantrine in DMSO:water (1:9 v/v) solution (reference solution). A bioavailability study of lumefantrine was conducted in a mouse model in fed and fasted states. When using the reference solution, the bioavailability of the lumefantrine heavily depended on food intake, resulting in a 2.7 times higher bioavailability in the fed state when compared to the fasted state. It also showed large between-subject variability. When formulated using Pro-Pheroid, the bioavailability of lumefantrine was 3.5 times higher as compared to lumefantrine in the reference solution and fasting state. Pro-Pheroid also dramatically reduced the effects of food intake and the between-subject variability for bioavailability observed with the reference. In vivo antimalarial efficacy was also evaluated with lumefantrine formulated using Pro-Pheroid technology compared to the reference solution. The results indicated that lumefantrine in Pro-Pheroid formulation exhibited improved antimalarial activity in vitro by 46.8%, when compared to the reference. The results of the Peters' 4-day suppressive test indicated no significant difference in the efficacy or mean survival time of the mice in the Pro-Pheroid formulation and reference test groups when compared to the positive control, chloroquine. These findings suggest that using the Pro-Pheroid formulation improves the bioavailability of lumefantrine, eliminates the food effect associated with lumefantrine as well as significantly reduces the between subject variability in bioavailability when compared to the reference solution. Copyright © 2015 Elsevier B.V. All rights reserved.

Power maximization of variable-speed variable-pitch wind turbines using passive adaptive neural fault tolerant control

NASA Astrophysics Data System (ADS)

Habibi, Hamed; Rahimi Nohooji, Hamed; Howard, Ian

2017-09-01

Power maximization has always been a practical consideration in wind turbines. The question of how to address optimal power capture, especially when the system dynamics are nonlinear and the actuators are subject to unknown faults, is significant. This paper studies the control methodology for variable-speed variable-pitch wind turbines including the effects of uncertain nonlinear dynamics, system fault uncertainties, and unknown external disturbances. The nonlinear model of the wind turbine is presented, and the problem of maximizing extracted energy is formulated by designing the optimal desired states. With the known system, a model-based nonlinear controller is designed; then, to handle uncertainties, the unknown nonlinearities of the wind turbine are estimated by utilizing radial basis function neural networks. The adaptive neural fault tolerant control is designed passively to be robust on model uncertainties, disturbances including wind speed and model noises, and completely unknown actuator faults including generator torque and pitch actuator torque. The Lyapunov direct method is employed to prove that the closed-loop system is uniformly bounded. Simulation studies are performed to verify the effectiveness of the proposed method.

Integrated control-structure design

NASA Technical Reports Server (NTRS)

Hunziker, K. Scott; Kraft, Raymond H.; Bossi, Joseph A.

1991-01-01

A new approach for the design and control of flexible space structures is described. The approach integrates the structure and controller design processes thereby providing extra opportunities for avoiding some of the disastrous effects of control-structures interaction and for discovering new, unexpected avenues of future structural design. A control formulation based on Boyd's implementation of Youla parameterization is employed. Control design parameters are coupled with structural design variables to produce a set of integrated-design variables which are selected through optimization-based methodology. A performance index reflecting spacecraft mission goals and constraints is formulated and optimized with respect to the integrated design variables. Initial studies have been concerned with achieving mission requirements with a lighter, more flexible space structure. Details of the formulation of the integrated-design approach are presented and results are given from a study involving the integrated redesign of a flexible geostationary platform.

A programing system for research and applications in structural optimization

NASA Technical Reports Server (NTRS)

Sobieszczanski-Sobieski, J.; Rogers, J. L., Jr.

1981-01-01

The flexibility necessary for such diverse utilizations is achieved by combining, in a modular manner, a state-of-the-art optimization program, a production level structural analysis program, and user supplied and problem dependent interface programs. Standard utility capabilities in modern computer operating systems are used to integrate these programs. This approach results in flexibility of the optimization procedure organization and versatility in the formulation of constraints and design variables. Features shown in numerical examples include: variability of structural layout and overall shape geometry, static strength and stiffness constraints, local buckling failure, and vibration constraints.

Beverage and culture. "Zhourat", a multivariate analysis of the globalization of a herbal tea from the Middle East.

PubMed

Obón, Concepción; Rivera, Diego; Alcaraz, Francisco; Attieh, Latiffa

2014-08-01

The "Zhourat" herbal tea consists of a blend of wild flowers, herbs, leaves and fruits and is a typical beverage of Lebanon and Syria. We aim to evaluate cultural significance of "Zhourat", to determine cultural standards for its formulation including key ingredients and to determine acceptable variability levels in terms of number of ingredients and their relative proportions, in summary what is "Zhourat" and what is not "Zhourat" from an ethnobotanical perspective. For this purpose we develop a novel methodology to describe and analyse patterns of variation of traditional multi-ingredient herbal formulations, beverages and teas and to identify key ingredients, which are characteristics of a particular culture and region and to interpret health claims for the mixture. Factor analysis and hierarchical clustering techniques were used to display similarities between samples whereas salience index was used to determine the main ingredients which could help to distinguish a standard traditional blend from a global market-addressed formulation. The study revealed 77 main ingredients belonging to 71 different species of vascular plants. In spite of the "Zhourat's" highly variable content, the salience analysis resulted in a determined set of key botanical components including Rosa x damascena Herrm., Althaea damascena Mouterde, Matricaria chamomilla L., Aloysia citrodora Palau, Zea mays L. and Elaeagnus angustifolia L. The major health claims for "Zhourat" as digestive, sedative and for respiratory problems are culturally coherent with the analysis of the traditional medicinal properties uses of its ingredients. Copyright © 2014 Elsevier Ltd. All rights reserved.

CCM Continuity Constraint Method: A finite-element computational fluid dynamics algorithm for incompressible Navier-Stokes fluid flows

DOE Office of Scientific and Technical Information (OSTI.GOV)

Williams, P. T.

1993-09-01

As the field of computational fluid dynamics (CFD) continues to mature, algorithms are required to exploit the most recent advances in approximation theory, numerical mathematics, computing architectures, and hardware. Meeting this requirement is particularly challenging in incompressible fluid mechanics, where primitive-variable CFD formulations that are robust, while also accurate and efficient in three dimensions, remain an elusive goal. This dissertation asserts that one key to accomplishing this goal is recognition of the dual role assumed by the pressure, i.e., a mechanism for instantaneously enforcing conservation of mass and a force in the mechanical balance law for conservation of momentum. Provingmore » this assertion has motivated the development of a new, primitive-variable, incompressible, CFD algorithm called the Continuity Constraint Method (CCM). The theoretical basis for the CCM consists of a finite-element spatial semi-discretization of a Galerkin weak statement, equal-order interpolation for all state-variables, a 0-implicit time-integration scheme, and a quasi-Newton iterative procedure extended by a Taylor Weak Statement (TWS) formulation for dispersion error control. Original contributions to algorithmic theory include: (a) formulation of the unsteady evolution of the divergence error, (b) investigation of the role of non-smoothness in the discretized continuity-constraint function, (c) development of a uniformly H 1 Galerkin weak statement for the Reynolds-averaged Navier-Stokes pressure Poisson equation, (d) derivation of physically and numerically well-posed boundary conditions, and (e) investigation of sparse data structures and iterative methods for solving the matrix algebra statements generated by the algorithm.« less

Emission factors for fugitive dust from bulldozers working on a coal pile.

PubMed

Mueller, Stephen F; Mallard, Jonathan W; Mao, Qi; Shaw, Stephanie L

2015-01-01

A study of a Powder River Basin (PRB) coal pile found that fugitive emissions from natural and human activity each produced similar levels of downwind fine + coarse (i.e., smaller than 10 µm, or PM10) particle mass concentrations. Natural impacts were statistically removed from downwind measurements to estimate emission factor Ev for bulldozers working on the pile. The Ev determined here was similar in magnitude to emission factors (EFs) computed using a U.S. Environmental Protection Agency (EPA) formulation for unpaved surfaces at industrial sites, even though the latter was not based on data for coal piles. EF formulations from this study and those in the EPA guidance yield values of similar magnitude but differ in the variables used to compute Ev variations. EPA studies included effects of surface silt fraction and vehicle weight, while the present study captured the influence of coal moisture. Our data indicate that the relationship between PRB coal fugitive dust Ev (expressed as mass of PM10 emitted per minute of bulldozer operation) and coal moisture content Mc (in percent) at the study site is best expressed as Ev =10(f(Mc())) where f(Mc) is a function of moisture. This function was determined by statistical regression between log10(Ev) and Mc where both Ev and Mc are expressed as daily averages of observations based on 289 hours sampled during 44 days from late June through mid-November of 2012. A methodology is described that estimates Mc based on available meteorological data (precipitation amount and solar radiation flux). An example is given of computed variations in daily Ev for an entire year. This illustrates the sensitivity of the daily average particulate EF to meteorological variability at one location. Finally, a method is suggested for combining the moisture-sensitive formulation for Ev with the EPA formulation to accommodate a larger number of independent variables that influence fugitive emissions.

Exploring scientific creativity of eleventh-grade students in Taiwan

NASA Astrophysics Data System (ADS)

Liang, Jia-Chi

2002-04-01

Although most researchers focus on scientists' creativity, students' scientific creativity should be considered, especially for high school and college students. It is generally assumed that most professional creators in science emerge from amateur creators. Therefore, the purpose of this study is to investigate the relationship between students' scientific creativity and selected variables including creativity, problem finding, formulating hypotheses, science achievement, the nature of science, and attitudes toward science for finding significant predictors of eleventh grade students' scientific creativity. A total of 130 male eleventh-grade students in three biology classes participated in this study. The main instruments included the Test of Divergent Thinking (TDT) for creativity measurement, the Creativity Rating Scale (CRS) and the Creative Activities and Accomplishments Check Lists (CAACL ) for measurement of scientific creativity, the Nature of Scientific Knowledge Scale (NSKS) for measurement of the nature of science, and the Science Attitude Inventory II (SAI II) for measurement of attitudes toward science. In addition, two instruments on measuring students' abilities of problem finding and abilities of formulating hypotheses were developed by the researcher in this study. Data analysis involved descriptive statistics, Pearson product-moment correlations, and stepwise multiple regressions. The major findings suggested the following: (1) students' scientific creativity significantly correlated with some of selected variables such as attitudes toward science, problem finding, formulating hypotheses, the nature of science, resistance to closure, originality, and elaboration; (2) four significant predictors including attitudes toward science, problem finding, resistance to closure, and originality accounted for 48% of the variance of students' scientific creativity; (3) there were big differences between students with a higher and a lower degree of scientific creativity on the variables of family support, career images, and readings about science; and (4) many students were confused about the creative and moral levels on NSKS and the concept of "almighty of science" and purposes of science on SAI II. The results of this study may provide a more holistic and integrative interpretation of students' scientific creativity and propose better ways of evaluating students' scientific creativity. In addition, the research results may encourage teachers to view scientific creativity as an ability that can be enhanced through various means in classroom science teaching.

Enhanced Ungual Permeation of Terbinafine HCl Delivered Through Liposome-Loaded Nail Lacquer Formulation Optimized by QbD Approach.

PubMed

Shah, Viral H; Jobanputra, Amee

2018-01-01

The present investigation focused on developing, optimizing, and evaluating a novel liposome-loaded nail lacquer formulation for increasing the transungual permeation flux of terbinafine HCl for efficient treatment of onychomycosis. A three-factor, three-level, Box-Behnken design was employed for optimizing process and formulation parameters of liposomal formulation. Liposomes were formulated by thin film hydration technique followed by sonication. Drug to lipid ratio, sonication amplitude, and sonication time were screened as independent variables while particle size, PDI, entrapment efficiency, and zeta potential were selected as quality attributes for liposomal formulation. Multiple regression analysis was employed to construct a second-order quadratic polynomial equation and contour plots. Design space (overlay plot) was generated to optimize a liposomal system, with software-suggested levels of independent variables that could be transformed to desired responses. The optimized liposome formulation was characterized and dispersed in nail lacquer which was further evaluated for different parameters. Results depicted that the optimized terbinafine HCl-loaded liposome formulation exhibited particle size of 182 nm, PDI of 0.175, zeta potential of -26.8 mV, and entrapment efficiency of 80%. Transungual permeability flux of terbinafine HCl through liposome-dispersed nail lacquer formulation was observed to be significantly higher in comparison to nail lacquer with a permeation enhancer. The developed formulation was also observed to be as efficient as pure drug dispersion in its antifungal activity. Thus, it was concluded that the developed formulation can serve as an efficient tool for enhancing the permeability of terbinafine HCl across human nail plate thereby improving its therapeutic efficiency.

Drought risk assessment under climate change is sensitive to methodological choices for the estimation of evaporative demand

PubMed Central

Barsugli, Joseph J.; Hobbins, Michael T.; Kumar, Sanjiv

2017-01-01

Several studies have projected increases in drought severity, extent and duration in many parts of the world under climate change. We examine sources of uncertainty arising from the methodological choices for the assessment of future drought risk in the continental US (CONUS). One such uncertainty is in the climate models’ expression of evaporative demand (E0), which is not a direct climate model output but has been traditionally estimated using several different formulations. Here we analyze daily output from two CMIP5 GCMs to evaluate how differences in E0 formulation, treatment of meteorological driving data, choice of GCM, and standardization of time series influence the estimation of E0. These methodological choices yield different assessments of spatio-temporal variability in E0 and different trends in 21st century drought risk. First, we estimate E0 using three widely used E0 formulations: Penman-Monteith; Hargreaves-Samani; and Priestley-Taylor. Our analysis, which primarily focuses on the May-September warm-season period, shows that E0 climatology and its spatial pattern differ substantially between these three formulations. Overall, we find higher magnitudes of E0 and its interannual variability using Penman-Monteith, in particular for regions like the Great Plains and southwestern US where E0 is strongly influenced by variations in wind and relative humidity. When examining projected changes in E0 during the 21st century, there are also large differences among the three formulations, particularly the Penman-Monteith relative to the other two formulations. The 21st century E0 trends, particularly in percent change and standardized anomalies of E0, are found to be sensitive to the long-term mean value and the amplitude of interannual variability, i.e. if the magnitude of E0 and its interannual variability are relatively low for a particular E0 formulation, then the normalized or standardized 21st century trend based on that formulation is amplified relative to other formulations. This is the case for the use of Hargreaves-Samani and Priestley-Taylor, where future E0 trends are comparatively much larger than for Penman-Monteith. When comparing Penman-Monteith E0 responses between different choices of input variables related to wind speed, surface roughness, and net radiation, we found differences in E0 trends, although these choices had a much smaller influence on E0 trends than did the E0 formulation choices. These methodological choices and specific climate model selection, also have a large influence on the estimation of trends in standardized drought indices used for drought assessment operationally. We find that standardization tends to amplify divergences between the E0 trends calculated using different E0 formulations, because standardization is sensitive to both the climatology and amplitude of interannual variability of E0. For different methodological choices and GCM output considered in estimating E0, we examine potential sources of uncertainty in 21st century trends in the Standardized Precipitation Evapotranspiration Index (SPEI) and Evaporative Demand Drought Index (EDDI) over selected regions of the CONUS to demonstrate the practical implications of these methodological choices for the quantification of drought risk under climate change. PMID:28301603

The effect of operating and formulation variables on the morphology of spray-dried protein particles.

PubMed

Maa, Y F; Costantino, H R; Nguyen, P A; Hsu, C C

1997-08-01

The purpose of this research was to investigate the shape and morphology of various spray-dried protein powders as a function of spray-drying conditions and protein formulations. A benchtop spray dryer was used to spray dry three model proteins in formulation with a sugar or a surfactant. Physical characterizations of the powder included morphology (scanning electron microscopy), particle size, residual moisture, and X-ray powder diffraction analyses. A significant change in particle shape from irregular (e.g., "donut") to spherical was observed as the outlet temperature of the dryer was decreased. The drying air outlet temperature was shown to depend on various operating parameters and was found to correlate with the drying rate of atomized droplets in the drying chamber. The morphology of spray-dried protein particles was also affected by formulation. In protein:sugar formulations, spray-dried particles exhibited a smooth surface regardless of the protein-to-lactose ratio, whereas roughness was observed when mannitol was present at > 30% of total solids, due to recrystallization. Protein particles containing trehalose at concentrations > 50% were highly agglomerated. The presence of surfactant resulted in noticeably smoother, more spherical particles. The shape and the morphology of spray-dried powders are affected by spray drying conditions and protein formulation. This study provides information useful for development of dry proteins for fine powder (e.g., aerosol) applications.

The Graded Alluvial River: Variable Flow and the Dominant Discharge

NASA Astrophysics Data System (ADS)

Blom, A.; Arkesteijn, L.; Viparelli, E.

2016-12-01

We derive analytical formulations for the graded or equilibrium longitudinal profile of a mixed-sediment alluvial river under variable flow. The formulations are applicable to reaches upstream from the backwater zone. The model is based on the conservation equations for the mass of two distinct sediment modes, sand and gravel, at the bed surface to account for the effects of grain size selective transport and abrasion of gravel particles. The effects of a variable flow rate are included by (a) treating the flow as a continuously changing yet steady water discharge (i.e. here termed an alternating steady discharge) and (b) assuming the time scale of changes in channel slope and bed surface texture to be much larger than the one of changes in flow rate. The equations are simplified realizing that at equilibrium the river profile finds itself in a dynamic steady state with oscillations around constant mean values of channel slope and bed surface texture. A generalized sediment transport relation representing the stochastic nature of sediment transport allows for explicit or analytical solutions to the streamwise decrease of both the channel slope and the bed surface mean grain size under variable flow for reaches unaffected by backwater effects. This modelling approach also provides a definition of a channel-forming or dominant water discharge, i.e., that steady water discharge that is equivalent in its effect on the equilibrium channel slope to the full hydrograph.

Influence of resin formulation variables on bond quality of southern pine plywood

Treesearch

C. -Y. Hse

1972-01-01

Thirty-six resins, each with two replicates, were factorially prepared with three formulation variables: molar ratios of sodium hydroxide to phenol of 0.4, 0.7, and 1.0; levels of resin solids content of 37, 40, and 43 percent; and molar ratios of formaldehyde to phenol of 1.6, 1.9, 2.2, and 2.5. Glue bond quality decreased substantially with a change of NaOH/phenol...

Probabilistic finite elements for transient analysis in nonlinear continua

NASA Technical Reports Server (NTRS)

Liu, W. K.; Belytschko, T.; Mani, A.

1985-01-01

The probabilistic finite element method (PFEM), which is a combination of finite element methods and second-moment analysis, is formulated for linear and nonlinear continua with inhomogeneous random fields. Analogous to the discretization of the displacement field in finite element methods, the random field is also discretized. The formulation is simplified by transforming the correlated variables to a set of uncorrelated variables through an eigenvalue orthogonalization. Furthermore, it is shown that a reduced set of the uncorrelated variables is sufficient for the second-moment analysis. Based on the linear formulation of the PFEM, the method is then extended to transient analysis in nonlinear continua. The accuracy and efficiency of the method is demonstrated by application to a one-dimensional, elastic/plastic wave propagation problem. The moments calculated compare favorably with those obtained by Monte Carlo simulation. Also, the procedure is amenable to implementation in deterministic FEM based computer programs.

Correlation Between Fracture Network Properties and Stress Variability in Geological Media

NASA Astrophysics Data System (ADS)

Lei, Qinghua; Gao, Ke

2018-05-01

We quantitatively investigate the stress variability in fractured geological media under tectonic stresses. The fracture systems studied include synthetic fracture networks following power law length scaling and natural fracture patterns based on outcrop mapping. The stress field is derived from a finite-discrete element model, and its variability is analyzed using a set of mathematical formulations that honor the tensorial nature of stress data. We show that local stress perturbation, quantified by the Euclidean distance of a local stress tensor to the mean stress tensor, has a positive, linear correlation with local fracture intensity, defined as the total fracture length per unit area within a local sampling window. We also evaluate the stress dispersion of the entire stress field using the effective variance, that is, a scalar-valued measure of the overall stress variability. The results show that a well-connected fracture system under a critically stressed state exhibits strong local and global stress variabilities.

Model reduction method using variable-separation for stochastic saddle point problems

NASA Astrophysics Data System (ADS)

Jiang, Lijian; Li, Qiuqi

2018-02-01

In this paper, we consider a variable-separation (VS) method to solve the stochastic saddle point (SSP) problems. The VS method is applied to obtain the solution in tensor product structure for stochastic partial differential equations (SPDEs) in a mixed formulation. The aim of such a technique is to construct a reduced basis approximation of the solution of the SSP problems. The VS method attempts to get a low rank separated representation of the solution for SSP in a systematic enrichment manner. No iteration is performed at each enrichment step. In order to satisfy the inf-sup condition in the mixed formulation, we enrich the separated terms for the primal system variable at each enrichment step. For the SSP problems by regularization or penalty, we propose a more efficient variable-separation (VS) method, i.e., the variable-separation by penalty method. This can avoid further enrichment of the separated terms in the original mixed formulation. The computation of the variable-separation method decomposes into offline phase and online phase. Sparse low rank tensor approximation method is used to significantly improve the online computation efficiency when the number of separated terms is large. For the applications of SSP problems, we present three numerical examples to illustrate the performance of the proposed methods.

A variable-gain output feedback control design approach

NASA Technical Reports Server (NTRS)

Haylo, Nesim

1989-01-01

A multi-model design technique to find a variable-gain control law defined over the whole operating range is proposed. The design is formulated as an optimal control problem which minimizes a cost function weighing the performance at many operating points. The solution is obtained by embedding into the Multi-Configuration Control (MCC) problem, a multi-model robust control design technique. In contrast to conventional gain scheduling which uses a curve fit of single model designs, the optimal variable-gain control law stabilizes the plant at every operating point included in the design. An iterative algorithm to compute the optimal control gains is presented. The methodology has been successfully applied to reconfigurable aircraft flight control and to nonlinear flight control systems.

Application of design of experiments for formulation development and mechanistic evaluation of iontophoretic tacrine hydrochloride delivery.

PubMed

Patel, Niketkumar; Jain, Shashank; Madan, Parshotam; Lin, Senshang

2016-11-01

The objective of this investigation is to develop mathematical equation to understand the impact of variables and establish statistical control over transdermal iontophoretic delivery of tacrine hydrochloride. In addition, possibility of using conductivity measurements as a tool of predicting ionic mobility of the participating ions for the application of iontophoretic delivery was explored. Central composite design was applied to study effect of independent variables like current strength, buffer molarity, and drug concentration on iontophoretic tacrine permeation flux. Molar conductivity was determined to evaluate electro-migration of tacrine ions with application of Kohlrausch's law. The developed mathematic equation not only reveals drug concentration as the most significant variable regulating tacrine permeation, followed by current strength and buffer molarity, but also is capable to optimize tacrine permeation with respective combination of independent variables to achieve desired therapeutic plasma concentration of tacrine in treatment of Alzheimer's disease. Moreover, relative higher mobility of sodium and chloride ions was observed as compared to estimated tacrine ion mobility. This investigation utilizes the design of experiment approach and extends the primary understanding of imapct of electronic and formulation variables on the tacrine permeation for the formulation development of iontophoretic tacrine delivery.

Optimization of physicochemical and textural properties of pizza cheese fortified with soybean oil and carrot extract.

PubMed

Motevalizadeh, Ehsan; Mortazavi, Seyed Ali; Milani, Elnaz; Hooshmand-Dalir, Moosa Al-Reza

2018-03-01

Response surface methodology (RSM) was used to optimize pizza cheese containing carrot extract. The effects of two important independent variables including soybean oil (5%-20%) and carrot extract (5%-20%) were studied on physicochemical and textural properties of pizza cheese containing carrot extract. According to the results, RSM was successfully used for optimizing formulation of pizza cheese containing carrot juice. Results of this study revealed that oil (A), carrot (B), AB, square term of carrot (B 2 ), B, AB, square term of oil (A 2 ), B 2 , AB, AB, A 2 B, A 2 , A 2 , A, A 2 , A 2 , AB, and AB 2 had the most effect on moisture, acidity, stretch, L*, a*, b*, hardness, meltability, springiness, peroxide value (PV), cohesiveness, chewiness, gumminess, fracture force, adhesiveness force, stiffness, flavor, and overall acceptability, respectively. A formulation upon 20% oil and 10.88% carrot extract was found as the optimal formulation for pizza cheese containing carrot extract. At the optimal formulation, PV, L*, a*, b*, meltability, stretch, cohesiveness, springiness, gumminess, chewiness, adhesive force, flavor, texture, and overall acceptability at the optimum formulation were measured 2.23, 82.51, -3.69, 18.05, 17.86, 85.61, 0.41, 7.874, 23.7, 0.27, 0.61, 3.50, 3.95, and 3.65, respectively.

Epidemiological trends for hospital admissions for acute rotavirus gastroenteritis in Belgium following the introduction of routine rotavirus vaccination and the subsequent switch from lyophilized to liquid formulation of Rotarix™.

PubMed

Raes, M; Strens, D; Kleintjens, J; Biundo, E; Morel, T; Vyse, A

2016-10-01

This study describes epidemiological trends for acute rotavirus gastroenteritis (RVGE) in Belgium in children aged ⩽5 years during the period June 2007 to May 2014 after the introduction of routine rotavirus (RV) vaccination. This period encompassed the switch from lyophilized to the liquid formulation of Rotarix™ (GlaxoSmithKline, Belgium) in August 2011. Uptake of RV vaccine remained consistently high throughout the study period with Rotarix the brand most often used. RV was present in 9% (1139/12 511) of hospitalized cases with acute gastroenteritis included in the study. Epidemiological trends for hospital admissions for RVGE remained consistent throughout the study period, with no evidence of any change associated with the switch from lyophilized to liquid formulation of Rotarix. This suggests both formulations perform similarly, with the liquid formulation not inferior regarding ability to reduce hospital admissions for acute RVGE in children aged ⩽5 years. A strong seasonal effect was observed with most RVGE occurring in the winter months but with some variability in intensity, with highest incidence found in those aged 6-24 months. The main observation was the decreased number of hospital admissions for RVGE in Belgium that occurred during winter 2013/2014.

Multi-Objective Trajectory Optimization of a Hypersonic Reconnaissance Vehicle with Temperature Constraints

NASA Astrophysics Data System (ADS)

Masternak, Tadeusz J.

This research determines temperature-constrained optimal trajectories for a scramjet-based hypersonic reconnaissance vehicle by developing an optimal control formulation and solving it using a variable order Gauss-Radau quadrature collocation method with a Non-Linear Programming (NLP) solver. The vehicle is assumed to be an air-breathing reconnaissance aircraft that has specified takeoff/landing locations, airborne refueling constraints, specified no-fly zones, and specified targets for sensor data collections. A three degree of freedom scramjet aircraft model is adapted from previous work and includes flight dynamics, aerodynamics, and thermal constraints. Vehicle control is accomplished by controlling angle of attack, roll angle, and propellant mass flow rate. This model is incorporated into an optimal control formulation that includes constraints on both the vehicle and mission parameters, such as avoidance of no-fly zones and coverage of high-value targets. To solve the optimal control formulation, a MATLAB-based package called General Pseudospectral Optimal Control Software (GPOPS-II) is used, which transcribes continuous time optimal control problems into an NLP problem. In addition, since a mission profile can have varying vehicle dynamics and en-route imposed constraints, the optimal control problem formulation can be broken up into several "phases" with differing dynamics and/or varying initial/final constraints. Optimal trajectories are developed using several different performance costs in the optimal control formulation: minimum time, minimum time with control penalties, and maximum range. The resulting analysis demonstrates that optimal trajectories that meet specified mission parameters and constraints can be quickly determined and used for larger-scale operational and campaign planning and execution.

A dual potential formulation of the Navier-Stokes equations

NASA Technical Reports Server (NTRS)

Gegg, S. G.; Pletcher, R. H.; Steger, J. L.

1989-01-01

A dual potential formulation for numerically solving the Navier-Stokes equations is developed and presented. The velocity field is decomposed using a scalar and vector potential. Vorticity and dilatation are used as the dependent variables in the momentum equations. Test cases in two dimensions verify the capability to solve flows using approximations from potential flow to full Navier-Stokes simulations. A three-dimensional incompressible flow formulation is also described. An interesting feature of this approach to solving the Navier-Stokes equations is the decomposition of the velocity field into a rotational part (vector potential) and an irrotational part (scalar potential). The Helmholtz decomposition theorem allows this splitting of the velocity field. This approach has had only limited use since it increases the number of dependent variables in the solution. However, it has often been used for incompressible flows where the solution scheme is known to be fast and accurate. This research extends the usage of this method to fully compressible Navier-Stokes simulations by using the dilatation variable along with vorticity. A time-accurate, iterative algorithm is used for the uncoupled solution of the governing equations. Several levels of flow approximation are available within the framework of this method. Potential flow, Euler and full Navier-Stokes solutions are possible using the dual potential formulation. Solution efficiency can be enhanced in a straightforward way. For some flows, the vorticity and/or dilatation may be negligible in certain regions (e.g., far from a viscous boundary in an external flow). It is possible to drop the calculation of these variables then and optimize the solution speed. Also, efficient Poisson solvers are available for the potentials. The relative merits of non-primitive variables versus primitive variables for solution of the Navier-Stokes equations are also discussed.

A Generalized Subsurface Flow Parameterization Considering Subgrid Spatial Variability of Recharge and Topography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Maoyi; Liang, Xu; Leung, Lai R.

2008-12-05

Subsurface flow is an important hydrologic process and a key component of the water budget, especially in humid regions. In this study, a new subsurface flow formulation is developed that incorporates spatial variability of both topography and recharge. It is shown through theoretical derivation and case studies that the power law and exponential subsurface flow parameterizations and the parameterization proposed by Woods et al.[1997] are all special cases of the new formulation. The subsurface flows calculated using the new formulation compare well with values derived from observations at the Tulpehocken Creek and Walnut Creek watersheds. Sensitivity studies show that whenmore » the spatial variability of topography or recharge, or both is increased, the subsurface flows increase at the two aforementioned sites and the Maimai hillslope. This is likely due to enhancement of interactions between the groundwater table and the land surface that reduce the flow path. An important conclusion of this study is that the spatial variability of recharge alone, and/or in combination with the spatial variability of topography can substantially alter the behaviors of subsurface flows. This suggests that in macroscale hydrologic models or land surface models, subgrid variations of recharge and topography can make significant contributions to the grid mean subsurface flow and must be accounted for in regions with large surface heterogeneity. This is particularly true for regions with humid climate and relatively shallow groundwater table where the combined impacts of spatial variability of recharge and topography are shown to be more important. For regions with arid climate and relatively deep groundwater table, simpler formulations, especially the power law, for subsurface flow can work well, and the impacts of subgrid variations of recharge and topography may be ignored.« less

Phase-field modeling of fracture in variably saturated porous media

NASA Astrophysics Data System (ADS)

Cajuhi, T.; Sanavia, L.; De Lorenzis, L.

2018-03-01

We propose a mechanical and computational model to describe the coupled problem of poromechanics and cracking in variably saturated porous media. A classical poromechanical formulation is adopted and coupled with a phase-field formulation for the fracture problem. The latter has the advantage of being able to reproduce arbitrarily complex crack paths without introducing discontinuities on a fixed mesh. The obtained simulation results show good qualitative agreement with desiccation experiments on soils from the literature.

Design and statistical optimization of glipizide loaded lipospheres using response surface methodology.

PubMed

Shivakumar, Hagalavadi Nanjappa; Patel, Pragnesh Bharat; Desai, Bapusaheb Gangadhar; Ashok, Purnima; Arulmozhi, Sinnathambi

2007-09-01

A 32 factorial design was employed to produce glipizide lipospheres by the emulsification phase separation technique using paraffin wax and stearic acid as retardants. The effect of critical formulation variables, namely levels of paraffin wax (X1) and proportion of stearic acid in the wax (X2) on geometric mean diameter (dg), percent encapsulation efficiency (% EE), release at the end of 12 h (rel12) and time taken for 50% of drug release (t50), were evaluated using the F-test. Mathematical models containing only the significant terms were generated for each response parameter using the multiple linear regression analysis (MLRA) and analysis of variance (ANOVA). Both formulation variables studied exerted a significant influence (p < 0.05) on the response parameters. Numerical optimization using the desirability approach was employed to develop an optimized formulation by setting constraints on the dependent and independent variables. The experimental values of dg, % EE, rel12 and t50 values for the optimized formulation were found to be 57.54 +/- 1.38 mum, 86.28 +/- 1.32%, 77.23 +/- 2.78% and 5.60 +/- 0.32 h, respectively, which were in close agreement with those predicted by the mathematical models. The drug release from lipospheres followed first-order kinetics and was characterized by the Higuchi diffusion model. The optimized liposphere formulation developed was found to produce sustained anti-diabetic activity following oral administration in rats.

An efficient variable projection formulation for separable nonlinear least squares problems.

PubMed

Gan, Min; Li, Han-Xiong

2014-05-01

We consider in this paper a class of nonlinear least squares problems in which the model can be represented as a linear combination of nonlinear functions. The variable projection algorithm projects the linear parameters out of the problem, leaving the nonlinear least squares problems involving only the nonlinear parameters. To implement the variable projection algorithm more efficiently, we propose a new variable projection functional based on matrix decomposition. The advantage of the proposed formulation is that the size of the decomposed matrix may be much smaller than those of previous ones. The Levenberg-Marquardt algorithm using finite difference method is then applied to minimize the new criterion. Numerical results show that the proposed approach achieves significant reduction in computing time.

Formulation design and optimization of mouth dissolve tablets of nimesulide using vacuum drying technique.

PubMed

Gohel, Mukesh; Patel, Madhabhai; Amin, Avani; Agrawal, Ruchi; Dave, Rikita; Bariya, Nehal

2004-04-26

The purpose of this research was to develop mouth dissolve tablets of nimesulide. Granules containing nimesulide, camphor, crospovidone, and lactose were prepared by wet granulation technique. Camphor was sublimed from the dried granules by exposure to vacuum. The porous granules were then compressed. Alternatively, tablets were first prepared and later exposed to vacuum. The tablets were evaluated for percentage friability, wetting time, and disintegration time. In the investigation, a 32 full factorial design was used to investigate the joint influence of 2 formulation variables: amount of camphor and crospovidone. The results of multiple linear regression analysis revealed that for obtaining a rapidly disintegrating dosage form, tablets should be prepared using an optimum concentration of camphor and a higher percentage of crospovidone. A contour plot is also presented to graphically represent the effect of the independent variables on the disintegration time and percentage friability. A checkpoint batch was also prepared to prove the validity of the evolved mathematical model. Sublimation of camphor from tablets resulted in superior tablets as compared with the tablets prepared from granules that were exposed to vacuum. The systematic formulation approach helped in understanding the effect of formulation processing variables.

Multidimensional Methods for the Formulation of Biopharmaceuticals and Vaccines

PubMed Central

Maddux, Nathaniel R.; Joshi, Sangeeta B.; Volkin, David B.; Ralston, John P.; Middaugh, C. Russell

2013-01-01

Determining and preserving the higher order structural integrity and conformational stability of proteins, plasmid DNA and macromolecular complexes such as viruses, virus-like particles and adjuvanted antigens is often a significant barrier to the successful stabilization and formulation of biopharmaceutical drugs and vaccines. These properties typically must be investigated with multiple lower resolution experimental methods, since each technique monitors only a narrow aspect of the overall conformational state of a macromolecular system. This review describes the use of empirical phase diagrams (EPDs) to combine large amounts of data from multiple high-throughput instruments and construct a map of a target macromolecule's physical state as a function of temperature, solvent conditions, and other stress variables. We present a tutorial on the mathematical methodology, an overview of some of the experimental methods typically used, and examples of some of the previous major formulation applications. We also explore novel applications of EPDs including potential new mathematical approaches as well as possible new biopharmaceutical applications such as analytical comparability, chemical stability, and protein dynamics. PMID:21647886

Integrated stoichiometric, thermodynamic and kinetic modelling of steady state metabolism

PubMed Central

Fleming, R.M.T.; Thiele, I.; Provan, G.; Nasheuer, H.P.

2010-01-01

The quantitative analysis of biochemical reactions and metabolites is at frontier of biological sciences. The recent availability of high-throughput technology data sets in biology has paved the way for new modelling approaches at various levels of complexity including the metabolome of a cell or an organism. Understanding the metabolism of a single cell and multi-cell organism will provide the knowledge for the rational design of growth conditions to produce commercially valuable reagents in biotechnology. Here, we demonstrate how equations representing steady state mass conservation, energy conservation, the second law of thermodynamics, and reversible enzyme kinetics can be formulated as a single system of linear equalities and inequalities, in addition to linear equalities on exponential variables. Even though the feasible set is non-convex, the reformulation is exact and amenable to large-scale numerical analysis, a prerequisite for computationally feasible genome scale modelling. Integrating flux, concentration and kinetic variables in a unified constraint-based formulation is aimed at increasing the quantitative predictive capacity of flux balance analysis. Incorporation of experimental and theoretical bounds on thermodynamic and kinetic variables ensures that the predicted steady state fluxes are both thermodynamically and biochemically feasible. The resulting in silico predictions are tested against fluxomic data for central metabolism in E. coli and compare favourably with in silico prediction by flux balance analysis. PMID:20230840

Further improvements of a new model for turbulent convection in stars

NASA Technical Reports Server (NTRS)

Canuto, V. M.; Mazzitelli, I.

1992-01-01

The effects of including a variable molecular weight and of using the newest opacities of Rogers and Iglesias (1991) as inputs to a recent model by Canuto and Mazzitelli (1991) for stellar turbulent convection are studied. Solar evolutionary tracks are used to conclude that the the original model for turbulence with mixing length Lambda = z, Giuli's variable Q unequal to 1 and the new opacities yields a fit to solar T(eff) within 0.5 percent. A formulation of Lambda is proposed that extends the purely nonlocal Lambda = z expression to include local effects. A new expression for Lambda is obtained which generalizes both the mixing length theory (MLT) phenomenological expression for Lambda as well as the model Lambda = z. It is argued that the MLT should now be abandoned.

Synchronization of a Josephson junction array in terms of global variables

NASA Astrophysics Data System (ADS)

Vlasov, Vladimir; Pikovsky, Arkady

2013-08-01

We consider an array of Josephson junctions with a common LCR load. Application of the Watanabe-Strogatz approach [Physica DPDNPDT0167-278910.1016/0167-2789(94)90196-1 74, 197 (1994)] allows us to formulate the dynamics of the array via the global variables only. For identical junctions this is a finite set of equations, analysis of which reveals the regions of bistability of the synchronous and asynchronous states. For disordered arrays with distributed parameters of the junctions, the problem is formulated as an integro-differential equation for the global variables; here stability of the asynchronous states and the properties of the transition synchrony-asynchrony are established numerically.

Nonlinear probabilistic finite element models of laminated composite shells

NASA Technical Reports Server (NTRS)

Engelstad, S. P.; Reddy, J. N.

1993-01-01

A probabilistic finite element analysis procedure for laminated composite shells has been developed. A total Lagrangian finite element formulation, employing a degenerated 3-D laminated composite shell with the full Green-Lagrange strains and first-order shear deformable kinematics, forms the modeling foundation. The first-order second-moment technique for probabilistic finite element analysis of random fields is employed and results are presented in the form of mean and variance of the structural response. The effects of material nonlinearity are included through the use of a rate-independent anisotropic plasticity formulation with the macroscopic point of view. Both ply-level and micromechanics-level random variables can be selected, the latter by means of the Aboudi micromechanics model. A number of sample problems are solved to verify the accuracy of the procedures developed and to quantify the variability of certain material type/structure combinations. Experimental data is compared in many cases, and the Monte Carlo simulation method is used to check the probabilistic results. In general, the procedure is quite effective in modeling the mean and variance response of the linear and nonlinear behavior of laminated composite shells.

A computer code for multiphase all-speed transient flows in complex geometries. MAST version 1.0

NASA Technical Reports Server (NTRS)

Chen, C. P.; Jiang, Y.; Kim, Y. M.; Shang, H. M.

1991-01-01

The operation of the MAST code, which computes transient solutions to the multiphase flow equations applicable to all-speed flows, is described. Two-phase flows are formulated based on the Eulerian-Lagrange scheme in which the continuous phase is described by the Navier-Stokes equation (or Reynolds equations for turbulent flows). Dispersed phase is formulated by a Lagrangian tracking scheme. The numerical solution algorithms utilized for fluid flows is a newly developed pressure-implicit algorithm based on the operator-splitting technique in generalized nonorthogonal coordinates. This operator split allows separate operation on each of the variable fields to handle pressure-velocity coupling. The obtained pressure correction equation has the hyperbolic nature and is effective for Mach numbers ranging from the incompressible limit to supersonic flow regimes. The present code adopts a nonstaggered grid arrangement; thus, the velocity components and other dependent variables are collocated at the same grid. A sequence of benchmark-quality problems, including incompressible, subsonic, transonic, supersonic, gas-droplet two-phase flows, as well as spray-combustion problems, were performed to demonstrate the robustness and accuracy of the present code.

Computational Hemodynamics Involving Artificial Devices

NASA Technical Reports Server (NTRS)

Kwak, Dochan; Kiris, Cetin; Feiereisen, William (Technical Monitor)

2001-01-01

This paper reports the progress being made towards developing complete blood flow simulation capability in human, especially, in the presence of artificial devices such as valves and ventricular assist devices. Devices modeling poses unique challenges different from computing the blood flow in natural hearts and arteries. There are many elements needed such as flow solvers, geometry modeling including flexible walls, moving boundary procedures and physiological characterization of blood. As a first step, computational technology developed for aerospace applications was extended in the recent past to the analysis and development of mechanical devices. The blood flow in these devices is practically incompressible and Newtonian, and thus various incompressible Navier-Stokes solution procedures can be selected depending on the choice of formulations, variables and numerical schemes. Two primitive variable formulations used are discussed as well as the overset grid approach to handle complex moving geometry. This procedure has been applied to several artificial devices. Among these, recent progress made in developing DeBakey axial flow blood pump will be presented from computational point of view. Computational and clinical issues will be discussed in detail as well as additional work needed.

Pharmaceutical quality by design: product and process development, understanding, and control.

PubMed

Yu, Lawrence X

2008-04-01

The purpose of this paper is to discuss the pharmaceutical Quality by Design (QbD) and describe how it can be used to ensure pharmaceutical quality. The QbD was described and some of its elements identified. Process parameters and quality attributes were identified for each unit operation during manufacture of solid oral dosage forms. The use of QbD was contrasted with the evaluation of product quality by testing alone. The QbD is a systemic approach to pharmaceutical development. It means designing and developing formulations and manufacturing processes to ensure predefined product quality. Some of the QbD elements include: Defining target product quality profile; Designing product and manufacturing processes; Identifying critical quality attributes, process parameters, and sources of variability; Controlling manufacturing processes to produce consistent quality over time. Using QbD, pharmaceutical quality is assured by understanding and controlling formulation and manufacturing variables. Product testing confirms the product quality. Implementation of QbD will enable transformation of the chemistry, manufacturing, and controls (CMC) review of abbreviated new drug applications (ANDAs) into a science-based pharmaceutical quality assessment.

Prolonged release matrix tablet of pyridostigmine bromide: formulation and optimization using statistical methods.

PubMed

Bolourchian, Noushin; Rangchian, Maryam; Foroutan, Seyed Mohsen

2012-07-01

The aim of this study was to design and optimize a prolonged release matrix formulation of pyridostigmine bromide, an effective drug in myasthenia gravis and poisoning with nerve gas, using hydrophilic - hydrophobic polymers via D-optimal experimental design. HPMC and carnauba wax as retarding agents as well as tricalcium phosphate were used in matrix formulation and considered as independent variables. Tablets were prepared by wet granulation technique and the percentage of drug released at 1 (Y(1)), 4 (Y(2)) and 8 (Y(3)) hours were considered as dependent variables (responses) in this investigation. These experimental responses were best fitted for the cubic, cubic and linear models, respectively. The optimal formulation obtained in this study, consisted of 12.8 % HPMC, 24.4 % carnauba wax and 26.7 % tricalcium phosphate, had a suitable prolonged release behavior followed by Higuchi model in which observed and predicted values were very close. The study revealed that D-optimal design could facilitate the optimization of prolonged release matrix tablet containing pyridostigmine bromide. Accelerated stability studies confirmed that the optimized formulation remains unchanged after exposing in stability conditions for six months.

Genetic polymorphisms of LPL and HL and their association with the performance of Chinese sturgeons fed a formulated diet.

PubMed

He, Y; Shen, D; Liang, X F; Lu, R H; Xiao, H

2013-10-15

It is very important to investigate the reasons for the large individual differences in individual performance of food acceptance when using formulated diets for the successful culture of larvae and juveniles of the Chinese sturgeon Acipenser sinensis. Genetic differences of the mitochondrial control region were investigated by direct sequencing in two groups of Chinese sturgeon, which were apt to accept or refuse formulated diets. Among 968-bp sequences, 111 variable sites were identified. One variable site showed close association with the individual performance of specimens fed with formulated diets. The commercial diet for Chinese sturgeons usually contains high levels of lipids. Lipoprotein lipase (LPL) and hepatic lipase (HL) are two members of the lipase gene family, which are essential for the utilization of dietary lipid. Single nucleotide polymorphisms (SNPs) in intron 7 were detected in the two experimental groups of Chinese sturgeons. We were able to demonstrate that one SNP in the LPL gene and one SNP in the HL gene showed close association with the performance of sturgeons on the formulated diet.

Sound scattering by several zooplankton groups. II. Scattering models.

PubMed

Stanton, T K; Chu, D; Wiebe, P H

1998-01-01

Mathematical scattering models are derived and compared with data from zooplankton from several gross anatomical groups--fluidlike, elastic shelled, and gas bearing. The models are based upon the acoustically inferred boundary conditions determined from laboratory backscattering data presented in part I of this series [Stanton et al., J. Acoust. Soc. Am. 103, 225-235 (1998)]. The models use a combination of ray theory, modal-series solution, and distorted wave Born approximation (DWBA). The formulations, which are inherently approximate, are designed to include only the dominant scattering mechanisms as determined from the experiments. The models for the fluidlike animals (euphausiids in this case) ranged from the simplest case involving two rays, which could qualitatively describe the structure of target strength versus frequency for single pings, to the most complex case involving a rough inhomogeneous asymmetrically tapered bent cylinder using the DWBA-based formulation which could predict echo levels over all angles of incidence (including the difficult region of end-on incidence). The model for the elastic shelled body (gastropods in this case) involved development of an analytical model which takes into account irregularities and discontinuities of the shell. The model for gas-bearing animals (siphonophores) is a hybrid model which is composed of the summation of the exact solution to the gas sphere and the approximate DWBA-based formulation for arbitrarily shaped fluidlike bodies. There is also a simplified ray-based model for the siphonophore. The models are applied to data involving single pings, ping-to-ping variability, and echoes averaged over many pings. There is reasonable qualitative agreement between the predictions and single ping data, and reasonable quantitative agreement between the predictions and variability and averages of echo data.

Development of biology student worksheets to facilitate science process skills of student

NASA Astrophysics Data System (ADS)

Rahayu, Y. S.; Pratiwi, R.; Indana, S.

2018-01-01

This research aims to describe development of Biology student worksheets to facilitate science process skills of student, at the same time to facilitate thinking skills of students in senior high school are equipped with Assesment Sheets. The worksheets development refers to cycle which includes phase analysis (analysis), planning (planning), design (design), development (development), implementation (implementation), evaluation and revision (evaluation and revision). Phase evaluation and revision is an ongoing activity conducted in each phase of the development cycle. That is, after the evaluation of the results of these activities and make revisions at any phase, then continue to the next phase. Based on the test results for grade X, XI, and XII in St. Agnes Surabaya high school, obtained some important findings. The findings are as follows. (1) Developed biology student worksheets could be used to facilitate thinking ability of students in particular skills integrated process that includes components to formulate the problem, formulate hypotheses, determine the study variables, formulate an operational definition of variables, determine the steps in the research, planning data tables, organizing Data in the form of tables/charts, drawing conclusions, (2) Developed biology student worksheets could also facilitate the development of social interaction of students such as working together, listening/respect the opinions of others, assembling equipment and materials, discuss and share information and facilitate the upgrading of skills hands-on student activity. (3) Developed biology worksheets basically could be implemented with the guidance of the teacher step by step, especially for students who have never used a similar worksheet. Guidance at the beginning of this need, especially for worksheets that require special skills or understanding of specific concepts as a prerequisite, such as using a microscope, determine the heart rate, understand the mechanism of specific indicators.

Reducing nitrous oxide emissions by changing N fertiliser use from calcium ammonium nitrate (CAN) to urea based formulations.

PubMed

Harty, M A; Forrestal, P J; Watson, C J; McGeough, K L; Carolan, R; Elliot, C; Krol, D; Laughlin, R J; Richards, K G; Lanigan, G J

2016-09-01

The accelerating use of synthetic nitrogen (N) fertilisers, to meet the world's growing food demand, is the primary driver for increased atmospheric concentrations of nitrous oxide (N2O). The IPCC default emission factor (EF) for N2O from soils is 1% of the N applied, irrespective of its form. However, N2O emissions tend to be higher from nitrate-containing fertilisers e.g. calcium ammonium nitrate (CAN) compared to urea, particularly in regions, which have mild, wet climates and high organic matter soils. Urea can be an inefficient N source due to NH3 volatilisation, but nitrogen stabilisers (urease and nitrification inhibitors) can improve its efficacy. This study evaluated the impact of switching fertiliser formulation from calcium ammonium nitrate (CAN) to urea-based products, as a potential mitigation strategy to reduce N2O emissions at six temperate grassland sites on the island of Ireland. The surface applied formulations included CAN, urea and urea with the urease inhibitor N-(n-butyl) thiophosphoric triamide (NBPT) and/or the nitrification inhibitor dicyandiamide (DCD). Results showed that N2O emissions were significantly affected by fertiliser formulation, soil type and climatic conditions. The direct N2O emission factor (EF) from CAN averaged 1.49% overall sites, but was highly variable, ranging from 0.58% to 3.81. Amending urea with NBPT, to reduce ammonia volatilisation, resulted in an average EF of 0.40% (ranging from 0.21 to 0.69%)-compared to an average EF of 0.25% for urea (ranging from 0.1 to 0.49%), with both fertilisers significantly lower and less variable than CAN. Cumulative N2O emissions from urea amended with both NBPT and DCD were not significantly different from background levels. Switching from CAN to stabilised urea formulations was found to be an effective strategy to reduce N2O emissions, particularly in wet, temperate grassland. Copyright © 2016 Elsevier B.V. All rights reserved.

Azelaic acid foam 15% in the treatment of papulopustular rosacea: a randomized, double-blind, vehicle-controlled study.

PubMed

Draelos, Zoe Diana; Elewski, Boni; Staedtler, Gerald; Havlickova, Blanka

2013-12-01

Rosacea is a common chronic inflammatory skin disease that primarily affects facial skin. Its etiology is unknown, and currently there is no cure. Rosacea can be associated with severe symptoms, including transient erythema (flushing), nontransient erythema, papules, pustules, and telangiectases, leading to substantial discomfort and an unattractive appearance. This randomized, double-blind, vehicle-controlled, multicenter, parallel-group study conducted over 12 weeks with a 4-week follow-up period evaluated the efficacy and safety of a new formulation of azelaic acid (AzA) foam in a 15% concentration compared to vehicle alone in patients with papulopustular rosacea (PPR). Primary efficacy variables assessed were investigator global assessment (IGA) dichotomized into success and failure, and nominal change in inflammatory lesion count from baseline to end of treatment. Results indicated that the new foam formulation of AzA is effective and well-tolerated in a population of patients with PPR. Although no single formulation is appropriate for all patients, the development of a new foam formulation in addition to other available vehicles provides patients with options and allows health care providers to match the needs as well as preferences of individual patients and skin types with appropriate delivery modalities.

Prescribing and formulating neonatal intravenous feeding solutions by microcomputer.

PubMed Central

MacMahon, P

1984-01-01

This paper describes a computer programme for a low cost microcomputer designed to assist in the task of administering total parenteral nutrition to neonates: no knowledge of computers is necessary to operate the system. The programme displays recommended values for each of the total parenteral nutrition constituents that must be prescribed, based on detailed analysis of all the pertinent variables. The recommended values may be rejected but they do provide a useful prompt, especially for the more junior doctors. The programme includes a number of safeguards that protect against entering potentially dangerous values. As soon as the operator has completed the procedure of entering total parenteral nutrition requirements the calculations necessary to formulate a solution containing these are automatically performed. The print out contains this data plus instructions on the infusion rate and an analysis of the formulation's calorific content. This system makes it easier to vary the quantity of individual total parenteral nutrition constituents and time has been saved which was previously wasted performing laborious calculations. One of the most important contributions has been the virtual elimination of errors in the complex task of prescribing and formulating total parenteral nutrition for sick neonates. PMID:6430246

Formulation and optimization by experimental design of eco-friendly emulsions based on d-limonene.

PubMed

Pérez-Mosqueda, Luis M; Trujillo-Cayado, Luis A; Carrillo, Francisco; Ramírez, Pablo; Muñoz, José

2015-04-01

d-Limonene is a natural occurring solvent that can replace more pollutant chemicals in agrochemical formulations. In the present work, a comprehensive study of the influence of dispersed phase mass fraction, ϕ, and of the surfactant/oil ratio, R, on the emulsion stability and droplet size distribution of d-limonene-in-water emulsions stabilized by a non-ionic triblock copolymer surfactant has been carried out. An experimental full factorial design 3(2) was conducted in order to optimize the emulsion formulation. The independent variables, ϕ and R were studied in the range 10-50 wt% and 0.02-0.1, respectively. The emulsions studied were mainly destabilized by both creaming and Ostwald ripening. Therefore, initial droplet size and an overall destabilization parameter, the so-called turbiscan stability index, were used as dependent variables. The optimal formulation, comprising minimum droplet size and maximum stability was achieved at ϕ=50 wt%; R=0.062. Furthermore, the surface response methodology allowed us to obtain the formulation yielding sub-micron emulsions by using a single step rotor/stator homogenizer process instead of most commonly used two-step emulsification methods. In addition, the optimal formulation was further improved against Ostwald ripening by adding silicone oil to the dispersed phase. The combination of these experimental findings allowed us to gain a deeper insight into the stability of these emulsions, which can be applied to the rational development of new formulations with potential application in agrochemical formulations. Copyright © 2015 Elsevier B.V. All rights reserved.

Development of optimized self-nano-emulsifying drug delivery systems (SNEDDS) of carvedilol with enhanced bioavailability potential.

PubMed

Singh, Bhupinder; Khurana, Lalit; Bandyopadhyay, Shantanu; Kapil, Rishi; Katare, O O P

2011-11-01

Carvedilol, a widely prescribed cardiovascular drug for hypertension and congestive heart failure, exhibits low and variable bioavailability owing to poor absorption and extensive hepatic first-pass metabolism. The current research work, therefore, entails formulation development of liquid self-nano-emulsifying drug delivery systems (SNEDDS) to enhance the bioavailability of carvedilol by facilitating its transport via lymphatic circulation. The formulation constituents, i.e. lipids, surfactants, and co-surfactants, were selected on the basis of solubility studies. Pseudo-ternary phase diagrams were constructed to embark upon the selection of blend of lipidic (i.e. Capmul PG8) and hydrophilic components (i.e. Cremophor EL as surfactant and Transcutol HP as co-surfactant) for efficient and robust formulation of SNEDDS. The SNEDDS, systematically optimized employing a central composite design (CCD), were evaluated for various response variables viz drug release parameters, emulsification time, emulsion droplet size, and mean dissolution time. In vitro drug release studies depicted that the release from SNEDDS systems followed a non-Fickian kinetic behavior. The TEM imaging of the optimized formulation affirmed the uniform shape and nano size of the system. Accelerated studies of the optimized formulation indicated high stability of the formulation for 6 months. The in situ perfusion studies carried out in wistar rats construed several fold augmentation in the permeability and absorption potential of the optimized formulation vis-à-vis marketed formulation. Thus, the present studies ratified the potential of SNEDDS in augmenting the oral bioavailability of BCS class II drugs.

Frequency and Severity of Neutropenia Associated with Food and Drug Administration Approved and Compounded Formulations of Lomustine in Dogs with Cancer.

PubMed

Burton, J H; Stanley, S D; Knych, H K; Rodriguez, C O; Skorupski, K A; Rebhun, R B

2016-01-01

Compounded lomustine is used commonly in veterinary patients. However, the potential variability in these formulations is unknown and concern exists that compounded formulations of drugs may differ in potency from Food and Drug Administration (FDA)-approved products. The initial objective of this study was to evaluate the frequency and severity of neutropenia in dogs treated with compounded or FDA-approved formulations of lomustine. Subsequent analyses aimed to determine the potency of lomustine obtained from several compounding pharmacies. Thirty-seven dogs treated with FDA-approved or compounded lomustine. Dogs that received compounded or FDA-approved lomustine and had pretreatment and nadir CBCs performed were eligible for inclusion. Variables assessed included lomustine dose, neutrophil counts, and severity of neutropenia. Lomustine 5 mg capsules from 5 compounding sources were tested for potency using high-pressure liquid chromatography (HPLC) with ultraviolet (UV) detection. Twenty-one dogs received FDA-approved lomustine and 16 dogs were treated with lomustine prescribed from a single compounding pharmacy. All dogs treated with FDA-approved lomustine were neutropenic after treatment; 15 dogs (71%) developed grade 3 or higher neutropenia. Four dogs (25%) given compounded lomustine became neutropenic, with 2 dogs (12.5%) developing grade 3 neutropenia. The potency of lomustine from 5 compounding pharmacies ranged from 50 to 115% of the labeled concentration, with 1 sample within ±10% of the labeled concentration. These data support broader investigation into the potency and consistency of compounded chemotherapy drugs and highlight the potential need for greater oversight of these products. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Studies on a novel doughnut-shaped minitablet for intraocular drug delivery.

PubMed

Choonara, Yahya E; Pillay, Viness; Carmichael, Trevor; Danckwerts, Michael P

2007-12-28

The objective of this study was to evaluate the effect of 2 independent formulation variables on the drug release from a novel doughnut-shaped minitablet (DSMT) in order to optimize formulations for intraocular drug delivery. Formulations were based on a 3(2) full-factorial design. The 2 independent variables were the concentration of Resomer (% wt/wt) and the type of Resomer grade (RG502, RG503, and RG504), respectively. The evaluated response was the drug release rate constant computed from a referenced marketed product and in vitro drug release data obtained at pH 7.4 in simulated vitreous humor. DSMT devices were prepared containing either of 2 model drugs, ganciclovir or foscarnet, using a Manesty F3 tableting press fitted with a novel central-rod, punch, and die setup. Dissolution data revealed biphasic drug release behavior with 55% to 60% drug released over 120 days. The inherent viscosity of the various Resomer grades and the concentration were significant to achieve optimum release rate constants. Using the resultant statistical relationships with the release rate constant as a response, the optimum formulation predicted for devices formulated with foscarnet was 70% wt/wt of Resomer RG504, while 92% wt/wt of Resomer RG503 was ideal for devices formulated with ganciclovir. The results of this study revealed that the full-factorial design was a suitable tool to predict an optimized formulation for prolonged intraocular drug delivery.

Formulation and optimization of fast dissolving intraoral drug delivery system for clobazam using response surface methodology

PubMed Central

Bala, Rajni; Khanna, Sushil; Pawar, Pravin K.

2013-01-01

Clobazam is a newer 1,5-benzodiazepine used for the treatment of epilepsy. It is better tolerated and less sedating than other benzodiazepines. Absorption of the drug can be impacted by oral fast dissolving dosage form; this may have implications for epilepsy in pediatrics and those having difficulty in swallowing tablets/capsules resulting in improved patient compliance. The purpose of the present investigation was to formulate and optimize clobazam oro-dissolving tablets by direct compression method using response surface methodology (RSM). Oro-dispersible tablets of clobazam were prepared by direct compression method using crospovidone (2-6%) as a superdisintegrant, microcrystalline cellulose (MCC) (20-40%) was used as diluents along with directly compressible mannitol to enhance mouth feel. A 32 full factorial design was applied to investigate the combined effect of two formulation variables: amount of crospovidone and MCC over the independent variables disintegration time, wetting time and percent drug release. Disintegration time showed by all formulations was found to be in the range of 24.3-193 s based on evaluation parameters the formulation containing 6% of crospovidone and 30% of MCC showed promising performance against all other formulations. The results demonstrated that the RSM could efficiently be applied for the formulation of clobazam oro-dispersible tablets; therefore, constitute an advance in the management of epileptic attacks. PMID:24083203

Comparative study of flare control laws. [optimal control of b-737 aircraft approach and landing

NASA Technical Reports Server (NTRS)

Nadkarni, A. A.; Breedlove, W. J., Jr.

1979-01-01

A digital 3-D automatic control law was developed to achieve an optimal transition of a B-737 aircraft between various initial glid slope conditions and the desired final touchdown condition. A discrete, time-invariant, optimal, closed-loop control law presented for a linear regulator problem, was extended to include a system being acted upon by a constant disturbance. Two forms of control laws were derived to solve this problem. One method utilized the feedback of integral states defined appropriately and augmented with the original system equations. The second method formulated the problem as a control variable constraint, and the control variables were augmented with the original system. The control variable constraint control law yielded a better performance compared to feedback control law for the integral states chosen.

Genetic variability and differentiation among populations of the Azorean endemic gymnosperm Juniperus brevifolia: baseline information for a conservation and restoration perspective.

PubMed

Silva, Luís; Elias, Rui B; Moura, Mónica; Meimberg, Harald; Dias, Eduardo

2011-12-01

The Azorean endemic gymnosperm Juniperus brevifolia (Seub.) Antoine is a top priority species for conservation in Macaronesia, based on its ecological significance in natural plant communities. To evaluate genetic variability and differentiation among J. brevifolia populations from the Azorean archipelago, we studied 15 ISSR and 15 RAPD markers in 178 individuals from 18 populations. The average number of polymorphic bands per population was 65 for both ISSR and RAPD. The majority of genetic variability was found within populations and among populations within islands, and this partitioning of variability was confirmed by AMOVA. The large majority of population pairwise F(ST) values were above 0.3 and below 0.6. The degree of population genetic differentiation in J. brevifolia was relatively high compared with other species, including Juniperus spp. The genetic differentiation among populations suggests that provenance should be considered when formulating augmentation or reintroduction strategies.

Note on the ideal frame formulation

NASA Astrophysics Data System (ADS)

Lara, Martin

2017-09-01

An implementation of the ideal frame formulation of perturbed Keplerian motion is presented which only requires the integration of a differential system of dimension 7, contrary to the 8 variables traditionally integrated with this approach. The new formulation is based on the integration of a scaled version of the Eulerian set of redundant parameters and slightly improves runtime performance with respect to the 8-dimensional case while retaining comparable accuracy.

A data mining approach to optimize pellets manufacturing process based on a decision tree algorithm.

PubMed

Ronowicz, Joanna; Thommes, Markus; Kleinebudde, Peter; Krysiński, Jerzy

2015-06-20

The present study is focused on the thorough analysis of cause-effect relationships between pellet formulation characteristics (pellet composition as well as process parameters) and the selected quality attribute of the final product. The shape using the aspect ratio value expressed the quality of pellets. A data matrix for chemometric analysis consisted of 224 pellet formulations performed by means of eight different active pharmaceutical ingredients and several various excipients, using different extrusion/spheronization process conditions. The data set contained 14 input variables (both formulation and process variables) and one output variable (pellet aspect ratio). A tree regression algorithm consistent with the Quality by Design concept was applied to obtain deeper understanding and knowledge of formulation and process parameters affecting the final pellet sphericity. The clear interpretable set of decision rules were generated. The spehronization speed, spheronization time, number of holes and water content of extrudate have been recognized as the key factors influencing pellet aspect ratio. The most spherical pellets were achieved by using a large number of holes during extrusion, a high spheronizer speed and longer time of spheronization. The described data mining approach enhances knowledge about pelletization process and simultaneously facilitates searching for the optimal process conditions which are necessary to achieve ideal spherical pellets, resulting in good flow characteristics. This data mining approach can be taken into consideration by industrial formulation scientists to support rational decision making in the field of pellets technology. Copyright © 2015 Elsevier B.V. All rights reserved.

Design and In-vitro Evaluation of Sustained Release Floating Tablets of Metformin HCl Based on Effervescence and Swelling

PubMed Central

Senjoti, Faria Gias; Mahmood, Syed; Jaffri, Juliana Md; Mandal, Uttam Kumar

2016-01-01

An oral sustained-release floating tablet formulation of metformin HCl was designed and developed. Effervescence and swelling properties were attributed on the developed tablets by sodium bicarbonate and HPMC-PEO polymer combination, respectively. Tablet composition was optimized by response surface methodology (RSM). Seventeen (17) trial formulations were analyzed according to Box-Behnken design of experiment where polymer content of HPMC and PEO at 1: 4 ratio (A), amount of sodium bi-carbonate (B), and amount of SSG (C) were adopted as independent variables. Floating lag time in sec (Y1), cumulative percent drug released at 1 h (Y2) and 12 h (Y3) were chosen as response variables. Tablets from the optimized formulation were also stored at accelerated stability condition (40°C and 75% RH) for 3 months to assess their stability profile. RSM could efficiently optimize the tablet composition with excellent prediction ability. In-vitro drug release until 12 h, floating lag time, and duration of floating were dependent on the amount of three selected independent variables. Optimized tablets remained floating for more than 24 h with a floating lag time of less than 4 min. Based on best fitting method, optimized formulation was found to follow Korsmeyer-Peppas release kinetic. Accelerated stability study revealed that optimized formulation was stable for three months without any major changes in assay, dissolution profile, floating lag time and other physical properties. PMID:27610147

Multiple response optimization of processing and formulation parameters of Eudragit RL/RS-based matrix tablets for sustained delivery of diclofenac.

PubMed

Elzayat, Ehab M; Abdel-Rahman, Ali A; Ahmed, Sayed M; Alanazi, Fars K; Habib, Walid A; Sakr, Adel

2017-11-01

Multiple response optimization is an efficient technique to develop sustained release formulation while decreasing the number of experiments based on trial and error approach. Diclofenac matrix tablets were optimized to achieve a release profile conforming to USP monograph, matching Voltaren ® SR and withstand formulation variables. The percent of drug released at predetermined multiple time points were the response variables in the design. Statistical models were obtained with relative contour diagrams being overlaid to predict process and formulation parameters expected to produce the target release profile. Tablets were prepared by wet granulation using mixture of equivalent quantities of Eudragit RL/RS at overall polymer concentration of 10-30%w/w and compressed at 5-15KN. Drug release from the optimized formulation E4 (15%w/w, 15KN) was similar to Voltaren, conformed to USP monograph and found to be stable. Substituting lactose with mannitol, reversing the ratio between lactose and microcrystalline cellulose or increasing drug load showed no significant difference in drug release. Using dextromethorphan hydrobromide as a model soluble drug showed burst release due to higher solubility and formation of micro cavities. A numerical optimization technique was employed to develop a stable consistent promising formulation for sustained delivery of diclofenac.

C deg continuity elements by Hybrid Stress method. M.S. Thesis, 1982 Final Report

NASA Technical Reports Server (NTRS)

Kang, David Sung-Soo

1991-01-01

An intensive study of the assumed variable distribution necessary for the Assumed Displacement Formulation, the Hellinger-Reissner Formulation, and the Hu-Washizu Formulation is made in a unified manner. With emphasis on physical explanation, a systematic method for the Hybrid Stress element construction is outlined. The numerical examples use four and eight node plane stress elements and eight and twenty node solid elements. Computation cost study indicates that the hybrid stress element derived using recently developed Uncoupled Stress Formulation is comparable in CPU time to the Assumed Displacement element. Overall, main emphasis is placed on providing a broader understanding of the Hybrid Stress Formulation.

Advanced development of the boundary element method for elastic and inelastic thermal stress analysis. Ph.D. Thesis, 1987 Final Report

NASA Technical Reports Server (NTRS)

Henry, Donald P., Jr.

1991-01-01

The focus of this dissertation is on advanced development of the boundary element method for elastic and inelastic thermal stress analysis. New formulations for the treatment of body forces and nonlinear effects are derived. These formulations, which are based on particular integral theory, eliminate the need for volume integrals or extra surface integrals to account for these effects. The formulations are presented for axisymmetric, two and three dimensional analysis. Also in this dissertation, two dimensional and axisymmetric formulations for elastic and inelastic, inhomogeneous stress analysis are introduced. The derivatives account for inhomogeneities due to spatially dependent material parameters, and thermally induced inhomogeneities. The nonlinear formulation of the present work are based on an incremental initial stress approach. Two inelastic solutions algorithms are implemented: an iterative; and a variable stiffness type approach. The Von Mises yield criterion with variable hardening and the associated flow rules are adopted in these algorithms. All formulations are implemented in a general purpose, multi-region computer code with the capability of local definition of boundary conditions. Quadratic, isoparametric shape functions are used to model the geometry and field variables of the boundary (and domain) of the problem. The multi-region implementation permits a body to be modeled in substructured parts, thus dramatically reducing the cost of analysis. Furthermore, it allows a body consisting of regions of different (homogeneous) material to be studied. To test the program, results obtained for simple test cases are checked against their analytic solutions. Thereafter, a range of problems of practical interest are analyzed. In addition to displacement and traction loads, problems with body forces due to self-weight, centrifugal, and thermal loads are considered.

PD-PK evaluation of freeze-dried atorvastatin calcium-loaded poly-ε-caprolactone nanoparticles.

PubMed

Ahmed, Iman S; El-Hosary, Rania; Shalaby, Samia; Abd-Rabo, Marwa M; Elkhateeb, Dalia G; Nour, Samia

2016-05-17

In this work lyophilized poly-ε-caprolactone nanoparticles (NPs) loaded with atorvastatin calcium (AC) were developed in an attempt to improve the in-vivo performance of AC following oral administration. The individual and combined effects of several formulation variables were previously investigated using step-wise full factorial designs in order to produce optimized AC-NPs with predetermined characteristics including particle size, drug loading capacity, drug release profile and physical stability. Four optimized formulations were further subjected in this work to lyophilization to promote their long-term physical stability and were fully characterized. The pharmacodynamics (PD)/pharmacokinetics (PK) properties of two optimized freeze-dried AC-NPs formulations showing acceptable long-term stability were determined and compared to a marketed AC immediate release tablet (Lipitor(®)) in albino rats. PD results revealed that the two tested formulations were equally effective in reducing low density lipoproteins (LDL) and triglycerides (TG) levels when given in reduced doses compared to Lipitor(®) and showed no adverse effects. PK results, on the other hand, revealed that the two freeze-dried AC-NPs formulations were of significantly lower bioavailability compared to Lipitor(®). Taken together the PD and PK results demonstrate that the improved efficacy obtained at reduced doses from the freeze-dried AC-NPs could be due to increased concentration of AC in the liver rather than in the plasma. Copyright © 2016 Elsevier B.V. All rights reserved.

Canonical Formulation of Supermechanics

NASA Astrophysics Data System (ADS)

Matsumoto, S.

1990-07-01

The canonical formulation of a theory of dynamical systems with both Grassmann even and odd variables is investigated. The sufficient condition for the system being analytically solvable is given. The geodesic motion of a particle in the super Poincaré upper half plane is solved as an example.

Effect of formulation- and administration-related variables on deposition pattern of nasal spray pumps evaluated using a nasal cast.

PubMed

Kundoor, Vipra; Dalby, Richard N

2011-08-01

To systematically evaluate the effect of formulation- and administration-related variables on nasal spray deposition using a nasal cast. Deposition pattern was assessed by uniformly coating a transparent nose model with Sar-Gel®, which changes from white to purple on contact with water. Sprays were subsequently discharged into the cast, which was then digitally photographed. Images were quantified using Adobe® Photoshop. The effects of formulation viscosity (which influences droplet size), simulated administration techniques (head orientation, spray administration angle, spray nozzle insertion depth), spray pump design and metering volume on nasal deposition pattern were investigated. There was a significant decrease in the deposition area associated with sprays of increasing viscosity. This appeared to be mediated by an increase in droplet size and a narrowing of the spray plume. Administration techniques and nasal spray pump design also had a significant effect on the deposition pattern. This simple color-based method provides quantitative estimates of the effects that different formulation and administration variables may have on the nasal deposition area, and provides a rational basis on which manufacturers of nasal sprays can base their patient instructions or post approval changes when it is impractical to optimize these using a clinical study.

Enhancement of dissolution and oral bioavailability of lacidipine via pluronic P123/F127 mixed polymeric micelles: formulation, optimization using central composite design and in vivo bioavailability study.

PubMed

Fares, Ahmed R; ElMeshad, Aliaa N; Kassem, Mohamed A A

2018-11-01

This study aims at preparing and optimizing lacidipine (LCDP) polymeric micelles using thin film hydration technique in order to overcome LCDP solubility-limited oral bioavailability. A two-factor three-level central composite face-centered design (CCFD) was employed to optimize the formulation variables to obtain LCDP polymeric micelles of high entrapment efficiency and small and uniform particle size (PS). Formulation variables were: Pluronic to drug ratio (A) and Pluronic P123 percentage (B). LCDP polymeric micelles were assessed for entrapment efficiency (EE%), PS and polydispersity index (PDI). The formula with the highest desirability (0.959) was chosen as the optimized formula. The values of the formulation variables (A and B) in the optimized polymeric micelles formula were 45% and 80%, respectively. Optimum LCDP polymeric micelles had entrapment efficiency of 99.23%, PS of 21.08 nm and PDI of 0.11. Optimum LCDP polymeric micelles formula was physically characterized using transmission electron microscopy. LCDP polymeric micelles showed saturation solubility approximately 450 times that of raw LCDP in addition to significantly enhanced dissolution rate. Bioavailability study of optimum LCDP polymeric micelles formula in rabbits revealed a 6.85-fold increase in LCDP bioavailability compared to LCDP oral suspension.

A probabilistic model of a porous heat exchanger

NASA Technical Reports Server (NTRS)

Agrawal, O. P.; Lin, X. A.

1995-01-01

This paper presents a probabilistic one-dimensional finite element model for heat transfer processes in porous heat exchangers. The Galerkin approach is used to develop the finite element matrices. Some of the submatrices are asymmetric due to the presence of the flow term. The Neumann expansion is used to write the temperature distribution as a series of random variables, and the expectation operator is applied to obtain the mean and deviation statistics. To demonstrate the feasibility of the formulation, a one-dimensional model of heat transfer phenomenon in superfluid flow through a porous media is considered. Results of this formulation agree well with the Monte-Carlo simulations and the analytical solutions. Although the numerical experiments are confined to parametric random variables, a formulation is presented to account for the random spatial variations.

Kinetic and dynamic probability-density-function descriptions of disperse turbulent two-phase flows

NASA Astrophysics Data System (ADS)

Minier, Jean-Pierre; Profeta, Christophe

2015-11-01

This article analyzes the status of two classical one-particle probability density function (PDF) descriptions of the dynamics of discrete particles dispersed in turbulent flows. The first PDF formulation considers only the process made up by particle position and velocity Zp=(xp,Up) and is represented by its PDF p (t ;yp,Vp) which is the solution of a kinetic PDF equation obtained through a flux closure based on the Furutsu-Novikov theorem. The second PDF formulation includes fluid variables into the particle state vector, for example, the fluid velocity seen by particles Zp=(xp,Up,Us) , and, consequently, handles an extended PDF p (t ;yp,Vp,Vs) which is the solution of a dynamic PDF equation. For high-Reynolds-number fluid flows, a typical formulation of the latter category relies on a Langevin model for the trajectories of the fluid seen or, conversely, on a Fokker-Planck equation for the extended PDF. In the present work, a new derivation of the kinetic PDF equation is worked out and new physical expressions of the dispersion tensors entering the kinetic PDF equation are obtained by starting from the extended PDF and integrating over the fluid seen. This demonstrates that, under the same assumption of a Gaussian colored noise and irrespective of the specific stochastic model chosen for the fluid seen, the kinetic PDF description is the marginal of a dynamic PDF one. However, a detailed analysis reveals that kinetic PDF models of particle dynamics in turbulent flows described by statistical correlations constitute incomplete stand-alone PDF descriptions and, moreover, that present kinetic-PDF equations are mathematically ill posed. This is shown to be the consequence of the non-Markovian characteristic of the stochastic process retained to describe the system and the use of an external colored noise. Furthermore, developments bring out that well-posed PDF descriptions are essentially due to a proper choice of the variables selected to describe physical systems and guidelines are formulated to emphasize the key role played by the notion of slow and fast variables.

Holo-analysis.

PubMed

Rosen, G D

2006-06-01

Meta-analysis is a vague descriptor used to encompass very diverse methods of data collection analysis, ranging from simple averages to more complex statistical methods. Holo-analysis is a fully comprehensive statistical analysis of all available data and all available variables in a specified topic, with results expressed in a holistic factual empirical model. The objectives and applications of holo-analysis include software production for prediction of responses with confidence limits, translation of research conditions to praxis (field) circumstances, exposure of key missing variables, discovery of theoretically unpredictable variables and interactions, and planning future research. Holo-analyses are cited as examples of the effects on broiler feed intake and live weight gain of exogenous phytases, which account for 70% of variation in responses in terms of 20 highly significant chronological, dietary, environmental, genetic, managemental, and nutrient variables. Even better future accountancy of variation will be facilitated if and when authors of papers routinely provide key data for currently neglected variables, such as temperatures, complete feed formulations, and mortalities.

Formulation and characterization of an apigenin-phospholipid phytosome (APLC) for improved solubility, in vivo bioavailability, and antioxidant potential.

PubMed

Telange, Darshan R; Patil, Arun T; Pethe, Anil M; Fegade, Harshal; Anand, Sridhar; Dave, Vivek S

2017-10-15

The apigenin-phospholipid phytosome (APLC) was developed to improve the aqueous solubility, dissolution, in vivo bioavailability, and antioxidant activity of apigenin. The APLC synthesis was guided by a full factorial design strategy, incorporating specific formulation and process variables to deliver an optimized product. The design-optimized formulation was assayed for aqueous solubility, in vitro dissolution, pharmacokinetics, and antioxidant activity. The pharmacological evaluation was carried out by assessing its effects on carbon tetrachloride-induced elevation of liver function marker enzymes in a rat model. The antioxidant activity was assessed by studying its effects on the liver antioxidant marker enzymes. The developed model was validated using the design-optimized levels of formulation and process variables. The physical-chemical characterization confirmed the formation of phytosomes. The optimized formulation demonstrated over 36-fold higher aqueous solubility of apigenin, compared to that of pure apigenin. The formulation also exhibited a significantly higher rate and extent of apigenin release in dissolution studies. The pharmacokinetic analysis revealed a significant enhancement in the oral bioavailability of apigenin from the prepared formulation, compared to pure apigenin. The liver function tests indicated that the prepared phytosome showed a significantly improved restoration of all carbon tetrachloride-elevated rat liver function marker enzymes. The prepared formulation also exhibited antioxidant potential by significantly increasing the levels of glutathione, superoxide dismutase, catalase, and decreasing the levels of lipid peroxidase. The study shows that phospholipid-based phytosome is a promising and viable strategy for improving the delivery of apigenin and similar phytoconstituents with low aqueous solubility. Copyright © 2016 Elsevier B.V. All rights reserved.

Dissolution of Commercially Available Mesalamine Formulations at Various pH Levels.

PubMed

Tenjarla, Srini

2015-06-01

Mesalamine (5-aminosalicylic acid; 5-ASA) is recommended first-line therapy for mild-to-moderate ulcerative colitis. Many mesalamine formulations employ a pH-dependent release mechanism designed to maximize drug release in the colon. This study compared the in vitro release of 5-ASA from six commercially available mesalamine formulations at pH levels similar to those typically encountered in the human gastrointestinal tract. The release of 5-ASA from six mesalamine formulations [Mesalazin-Kohlpharma (Kohlpharma, Germany), Mesalazin-Eurim (Eurimpharm, Germany), Mesalazina-Faes (Faes Farma, Spain), Mesalazine EC (Actavis B.V., Netherlands), Mesalazine EC 500 PCH (Pharmachemie B.V., Netherlands); multimatrix mesalamine (Shire US Inc., USA)] was monitored separately at three different pH levels [1.0 (2 h), 6.4 (1 h), and 7.2 (8 h)] using United States Pharmacopeia dissolution apparatus II. The dissolution percentage was calculated as a mean of 12 units for each formulation. At pH 1.0 and 6.4, <1 % of 5-ASA release was observed for each of the mesalamine formulations tested. At pH 7.2, complete release of 5-ASA occurred within 1 h for Mesalazine EC and Mesalazine EC 500 PCH, and within 2 h for Mesalazin-Kohlpharma, Mesalazin-Eurim, and Mesalazina-Faes; complete release of 5-ASA from multimatrix mesalamine occurred within 7 h. Little variability in rate of 5-ASA dissolution was observed between tablets of each formulation. At pH 7.2, 5-ASA release profiles were variable among the commercially available mesalamine formulations that were tested.

Formulation and optimization of solid lipid nanoparticle formulation for pulmonary delivery of budesonide using Taguchi and Box-Behnken design.

PubMed

Emami, J; Mohiti, H; Hamishehkar, H; Varshosaz, J

2015-01-01

Budesonide is a potent non-halogenated corticosteroid with high anti-inflammatory effects. The lungs are an attractive route for non-invasive drug delivery with advantages for both systemic and local applications. The aim of the present study was to develop, characterize and optimize a solid lipid nanoparticle system to deliver budesonide to the lungs. Budesonide-loaded solid lipid nanoparticles were prepared by the emulsification-solvent diffusion method. The impact of various processing variables including surfactant type and concentration, lipid content organic and aqueous volume, and sonication time were assessed on the particle size, zeta potential, entrapment efficiency, loading percent and mean dissolution time. Taguchi design with 12 formulations along with Box-Behnken design with 17 formulations was developed. The impact of each factor upon the eventual responses was evaluated, and the optimized formulation was finally selected. The size and morphology of the prepared nanoparticles were studied using scanning electron microscope. Based on the optimization made by Design Expert 7(®) software, a formulation made of glycerol monostearate, 1.2 % polyvinyl alcohol (PVA), weight ratio of lipid/drug of 10 and sonication time of 90 s was selected. Particle size, zeta potential, entrapment efficiency, loading percent, and mean dissolution time of adopted formulation were predicted and confirmed to be 218.2 ± 6.6 nm, -26.7 ± 1.9 mV, 92.5 ± 0.52 %, 5.8 ± 0.3 %, and 10.4 ± 0.29 h, respectively. Since the preparation and evaluation of the selected formulation within the laboratory yielded acceptable results with low error percent, the modeling and optimization was justified. The optimized formulation co-spray dried with lactose (hybrid microparticles) displayed desirable fine particle fraction, mass median aerodynamic diameter (MMAD), and geometric standard deviation of 49.5%, 2.06 μm, and 2.98 μm; respectively. Our results provide fundamental data for the application of SLNs in pulmonary delivery system of budesonide.

Formulation and optimization of solid lipid nanoparticle formulation for pulmonary delivery of budesonide using Taguchi and Box-Behnken design

PubMed Central

Emami, J.; Mohiti, H.; Hamishehkar, H.; Varshosaz, J.

2015-01-01

Budesonide is a potent non-halogenated corticosteroid with high anti-inflammatory effects. The lungs are an attractive route for non-invasive drug delivery with advantages for both systemic and local applications. The aim of the present study was to develop, characterize and optimize a solid lipid nanoparticle system to deliver budesonide to the lungs. Budesonide-loaded solid lipid nanoparticles were prepared by the emulsification-solvent diffusion method. The impact of various processing variables including surfactant type and concentration, lipid content organic and aqueous volume, and sonication time were assessed on the particle size, zeta potential, entrapment efficiency, loading percent and mean dissolution time. Taguchi design with 12 formulations along with Box-Behnken design with 17 formulations was developed. The impact of each factor upon the eventual responses was evaluated, and the optimized formulation was finally selected. The size and morphology of the prepared nanoparticles were studied using scanning electron microscope. Based on the optimization made by Design Expert 7® software, a formulation made of glycerol monostearate, 1.2 % polyvinyl alcohol (PVA), weight ratio of lipid/drug of 10 and sonication time of 90 s was selected. Particle size, zeta potential, entrapment efficiency, loading percent, and mean dissolution time of adopted formulation were predicted and confirmed to be 218.2 ± 6.6 nm, -26.7 ± 1.9 mV, 92.5 ± 0.52 %, 5.8 ± 0.3 %, and 10.4 ± 0.29 h, respectively. Since the preparation and evaluation of the selected formulation within the laboratory yielded acceptable results with low error percent, the modeling and optimization was justified. The optimized formulation co-spray dried with lactose (hybrid microparticles) displayed desirable fine particle fraction, mass median aerodynamic diameter (MMAD), and geometric standard deviation of 49.5%, 2.06 μm, and 2.98 μm; respectively. Our results provide fundamental data for the application of SLNs in pulmonary delivery system of budesonide. PMID:26430454

Optimization and characterization of stable lipid-based, oxygen-filled microbubbles by mixture design.

PubMed

Polizzotti, Brian D; Thomson, Lindsay M; O'Connell, Daniel W; McGowan, Francis X; Kheir, John N

2014-08-01

Tissue hypoxia is a final common pathway that leads to cellular injury and death in a number of critical illnesses. Intravenous injections of self-assembling, lipid-based oxygen microbubbles (LOMs) can be used to deliver oxygen gas, preventing organ injury and death from systemic hypoxemia. However, current formulations exhibit high polydispersity indices (which may lead to microvascular obstruction) and poor shelf-lives, limiting the translational capacity of LOMs. In this study, we report our efforts to optimize LOM formulations using a mixture response surface methodology (mRSM). We study the effect of changing excipient proportions (the independent variables) on microbubble diameter and product loss (the dependent variables). By using mRSM analysis, the experimental data were fit using a reduced Scheffé linear mixture model. We demonstrate that formulations manufactured from 1,2-distearoyl-sn-glycero-3-phosphocholine, corn syrup, and water produce micron-sized microbubbles with low polydispersity indices, and decreased product loss (relative to previously described formulations) when stored at room temperature over a 30-day period. Optimized LOMs were subsequently tested for their oxygen-releasing ability and found to have similar release kinetics as prior formulations. © 2014 Wiley Periodicals, Inc.

State-Space Formulation for Circuit Analysis

ERIC Educational Resources Information Center

Martinez-Marin, T.

2010-01-01

This paper presents a new state-space approach for temporal analysis of electrical circuits. The method systematically obtains the state-space formulation of nondegenerate linear networks without using concepts of topology. It employs nodal/mesh systematic analysis to reduce the number of undesired variables. This approach helps students to…

A chance-constrained stochastic approach to intermodal container routing problems.

PubMed

Zhao, Yi; Liu, Ronghui; Zhang, Xi; Whiteing, Anthony

2018-01-01

We consider a container routing problem with stochastic time variables in a sea-rail intermodal transportation system. The problem is formulated as a binary integer chance-constrained programming model including stochastic travel times and stochastic transfer time, with the objective of minimising the expected total cost. Two chance constraints are proposed to ensure that the container service satisfies ship fulfilment and cargo on-time delivery with pre-specified probabilities. A hybrid heuristic algorithm is employed to solve the binary integer chance-constrained programming model. Two case studies are conducted to demonstrate the feasibility of the proposed model and to analyse the impact of stochastic variables and chance-constraints on the optimal solution and total cost.

A chance-constrained stochastic approach to intermodal container routing problems

PubMed Central

Zhao, Yi; Zhang, Xi; Whiteing, Anthony

2018-01-01

We consider a container routing problem with stochastic time variables in a sea-rail intermodal transportation system. The problem is formulated as a binary integer chance-constrained programming model including stochastic travel times and stochastic transfer time, with the objective of minimising the expected total cost. Two chance constraints are proposed to ensure that the container service satisfies ship fulfilment and cargo on-time delivery with pre-specified probabilities. A hybrid heuristic algorithm is employed to solve the binary integer chance-constrained programming model. Two case studies are conducted to demonstrate the feasibility of the proposed model and to analyse the impact of stochastic variables and chance-constraints on the optimal solution and total cost. PMID:29438389

A crystallographic model for the tensile and fatigue response for Rene N4 at 982 C

NASA Technical Reports Server (NTRS)

Sheh, M. Y.; Stouffer, D. C.

1990-01-01

An anisotropic constitutive model based on crystallographic slip theory was formulated for nickel-base single-crystal superalloys. The current equations include both drag stress and back stress state variables to model the local inelastic flow. Specially designed experiments have been conducted to evaluate the existence of back stress in single crystals. The results showed that the back stress effect of reverse inelastic flow on the unloading stress is orientation-dependent, and a back stress state variable in the inelastic flow equation is necessary for predicting inelastic behavior. Model correlations and predictions of experimental data are presented for the single crystal superalloy Rene N4 at 982 C.

Anisotropic constitutive modeling for nickel base single crystal superalloys using a crystallographic approach

NASA Technical Reports Server (NTRS)

Stouffer, D. C.; Sheh, M. Y.

1988-01-01

A micromechanical model based on crystallographic slip theory was formulated for nickel-base single crystal superalloys. The current equations include both drag stress and back stress state variables to model the local inelastic flow. Specially designed experiments have been conducted to evaluate the effect of back stress in single crystals. The results showed that (1) the back stress is orientation dependent; and (2) the back stress state variable in the inelastic flow equation is necessary for predicting anelastic behavior of the material. The model also demonstrated improved fatigue predictive capability. Model predictions and experimental data are presented for single crystal superalloy Rene N4 at 982 C.

Stomach specific polymeric low density microballoons as a vector for extended delivery of rabeprazole and amoxicillin for treatment of peptic ulcer.

PubMed

Choudhary, Sandeep; Jain, Ashay; Amin, Mohd Cairul Iqbal Mohd; Mishra, Vijay; Agrawal, Govind P; Kesharwani, Prashant

2016-05-01

The study was intended to develop a new intra-gastric floating in situ microballoons system for controlled delivery of rabeprazole sodium and amoxicillin trihydrate for the treatment of peptic ulcer disease. Eudragit S-100 and hydroxypropyl methyl cellulose based low density microballoons systems were fabricated by employing varying concentrations of Eudragit S-100 and hydroxypropyl methyl cellulose, to which varying concentrations of drug was added, and formulated by stirring at various speed and time to optimize the process and formulation variable. The formulation variables like concentration and ratio of polymers significantly affected the in vitro drug release from the prepared floating device. The validation of the gastro-retentive potential of the prepared microballoons was carried out in rabbits by orally administration of microballoons formulation containing radio opaque material. The developed formulations showed improved buoyancy and lower ulcer index as compared to that seen with plain drugs. Ulcer protective efficacies were confirmed in ulcer-bearing mouse model. In conclusion, greater compatibility, higher gastro-retention and higher anti-ulcer activity of the presently fabricated formulations to improve potential of formulation for redefining ulcer treatment are presented here. These learning exposed a targeted and sustained drug delivery potential of prepared microballoons in gastric region for ulcer therapeutic intervention as corroborated by in vitro and in vivo findings and, thus, deserves further attention for improved ulcer treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

Minimization search method for data inversion

NASA Technical Reports Server (NTRS)

Fymat, A. L.

1975-01-01

Technique has been developed for determining values of selected subsets of independent variables in mathematical formulations. Required computation time increases with first power of the number of variables. This is in contrast with classical minimization methods for which computational time increases with third power of the number of variables.

Scheduler Design Criteria: Requirements and Considerations

NASA Technical Reports Server (NTRS)

Lee, Hanbong

2016-01-01

This presentation covers fundamental requirements and considerations for developing schedulers in airport operations. We first introduce performance and functional requirements for airport surface schedulers. Among various optimization problems in airport operations, we focus on airport surface scheduling problem, including runway and taxiway operations. We then describe a basic methodology for airport surface scheduling such as node-link network model and scheduling algorithms previously developed. Next, we explain how to design a mathematical formulation in more details, which consists of objectives, decision variables, and constraints. Lastly, we review other considerations, including optimization tools, computational performance, and performance metrics for evaluation.

Eudragit E as excipient for production of granules and tablets from Phyllanthus niruri L spray-dried extract.

PubMed

Pereira de Souza, Tatiane; Martínez-Pacheco, Ramón; Gómez-Amoza, José Luiz; Petrovick, Pedro Ros

2007-04-27

The aim of this study was to investigate the feasibility of using Eudragit E as a granulating agent for a spray-dried extract from Phyllanthus niruri to obtain tablets containing a high dose of this product. The granules were developed by wet granulation and contained 2.5%, 5.0%, and 10.0% Eudragit E in the final product concentration. The tablets were produced on a single-punch tablet press by direct compression of granules using 0.5% magnesium stearate as a lubricant. The tablets were elaborated following a 2 x 3 factorial design, where Eudragit E concentration and compression force were the independent variables, and tensile strength and the extract release of the tablets were the dependent variables. All granules showed better technological properties than the spray-dried extract, including less moisture sorption. The characteristics of the granules were directly dependent on the proportion of Eudragit E in the formulation. In general, all tablets showed high mechanical resistance with less than 1% friability, less moisture sorption, and a slower extract release profile. The Eudragit E concentration and compression force of the tablets significantly influenced both dependent variables studied. In conclusion, Eudragit E was efficient as a granulating agent for the spray-dried extract, but additional studies are needed to further optimize the formulations in order to achieve less water sorption and improve the release of the extract from the tablets.

Methodology to develop crash modification functions for road safety treatments with fully specified and hierarchical models.

PubMed

Chen, Yongsheng; Persaud, Bhagwant

2014-09-01

Crash modification factors (CMFs) for road safety treatments are developed as multiplicative factors that are used to reflect the expected changes in safety performance associated with changes in highway design and/or the traffic control features. However, current CMFs have methodological drawbacks. For example, variability with application circumstance is not well understood, and, as important, correlation is not addressed when several CMFs are applied multiplicatively. These issues can be addressed by developing safety performance functions (SPFs) with components of crash modification functions (CM-Functions), an approach that includes all CMF related variables, along with others, while capturing quantitative and other effects of factors and accounting for cross-factor correlations. CM-Functions can capture the safety impact of factors through a continuous and quantitative approach, avoiding the problematic categorical analysis that is often used to capture CMF variability. There are two formulations to develop such SPFs with CM-Function components - fully specified models and hierarchical models. Based on sample datasets from two Canadian cities, both approaches are investigated in this paper. While both model formulations yielded promising results and reasonable CM-Functions, the hierarchical model was found to be more suitable in retaining homogeneity of first-level SPFs, while addressing CM-Functions in sub-level modeling. In addition, hierarchical models better capture the correlations between different impact factors. Copyright © 2014 Elsevier Ltd. All rights reserved.

Quality by design approach: application of artificial intelligence techniques of tablets manufactured by direct compression.

PubMed

Aksu, Buket; Paradkar, Anant; de Matas, Marcel; Ozer, Ozgen; Güneri, Tamer; York, Peter

2012-12-01

The publication of the International Conference of Harmonization (ICH) Q8, Q9, and Q10 guidelines paved the way for the standardization of quality after the Food and Drug Administration issued current Good Manufacturing Practices guidelines in 2003. "Quality by Design", mentioned in the ICH Q8 guideline, offers a better scientific understanding of critical process and product qualities using knowledge obtained during the life cycle of a product. In this scope, the "knowledge space" is a summary of all process knowledge obtained during product development, and the "design space" is the area in which a product can be manufactured within acceptable limits. To create the spaces, artificial neural networks (ANNs) can be used to emphasize the multidimensional interactions of input variables and to closely bind these variables to a design space. This helps guide the experimental design process to include interactions among the input variables, along with modeling and optimization of pharmaceutical formulations. The objective of this study was to develop an integrated multivariate approach to obtain a quality product based on an understanding of the cause-effect relationships between formulation ingredients and product properties with ANNs and genetic programming on the ramipril tablets prepared by the direct compression method. In this study, the data are generated through the systematic application of the design of experiments (DoE) principles and optimization studies using artificial neural networks and neurofuzzy logic programs.

On the Miller-Tucker-Zemlin Based Formulations for the Distance Constrained Vehicle Routing Problems

NASA Astrophysics Data System (ADS)

Kara, Imdat

2010-11-01

Vehicle Routing Problem (VRP), is an extension of the well known Traveling Salesman Problem (TSP) and has many practical applications in the fields of distribution and logistics. When the VRP consists of distance based constraints it is called Distance Constrained Vehicle Routing Problem (DVRP). However, the literature addressing on the DVRP is scarce. In this paper, existing two-indexed integer programming formulations, having Miller-Tucker-Zemlin based subtour elimination constraints, are reviewed. Existing formulations are simplified and obtained formulation is presented as formulation F1. It is shown that, the distance bounding constraints of the formulation F1, may not generate the distance traveled up to the related node. To do this, we redefine the auxiliary variables of the formulation and propose second formulation F2 with new and easy to use distance bounding constraints. Adaptation of the second formulation to the cases where new restrictions such as minimal distance traveled by each vehicle or other objectives such as minimizing the longest distance traveled is discussed.

A quality by design approach to understand formulation and process variability in pharmaceutical melt extrusion processes.

PubMed

Patwardhan, Ketaki; Asgarzadeh, Firouz; Dassinger, Thomas; Albers, Jessica; Repka, Michael A

2015-05-01

In this study, the principles of quality by design (QbD) have been uniquely applied to a pharmaceutical melt extrusion process for an immediate release formulation with a low melting model drug, ibuprofen. Two qualitative risk assessment tools - Fishbone diagram and failure mode effect analysis - were utilized to strategically narrow down the most influential parameters. Selected variables were further assessed using a Plackett-Burman screening study, which was upgraded to a response surface design consisting of the critical factors to study the interactions between the study variables. In process torque, glass transition temperature (Tg ) of the extrudates, assay, dissolution and phase change were measured as responses to evaluate the critical quality attributes (CQAs) of the extrudates. The effect of each study variable on the measured responses was analysed using multiple regression for the screening design and partial least squares for the optimization design. Experimental limits for formulation and process parameters to attain optimum processing have been outlined. A design space plot describing the domain of experimental variables within which the CQAs remained unchanged was developed. A comprehensive approach for melt extrusion product development based on the QbD methodology has been demonstrated. Drug loading concentrations between 40- 48%w/w and extrusion temperature in the range of 90-130°C were found to be the most optimum. © 2015 Royal Pharmaceutical Society.

Modeling variably saturated multispecies reactive groundwater solute transport with MODFLOW-UZF and RT3D

USGS Publications Warehouse

Bailey, Ryan T.; Morway, Eric D.; Niswonger, Richard G.; Gates, Timothy K.

2013-01-01

A numerical model was developed that is capable of simulating multispecies reactive solute transport in variably saturated porous media. This model consists of a modified version of the reactive transport model RT3D (Reactive Transport in 3 Dimensions) that is linked to the Unsaturated-Zone Flow (UZF1) package and MODFLOW. Referred to as UZF-RT3D, the model is tested against published analytical benchmarks as well as other published contaminant transport models, including HYDRUS-1D, VS2DT, and SUTRA, and the coupled flow and transport modeling system of CATHY and TRAN3D. Comparisons in one-dimensional, two-dimensional, and three-dimensional variably saturated systems are explored. While several test cases are included to verify the correct implementation of variably saturated transport in UZF-RT3D, other cases are included to demonstrate the usefulness of the code in terms of model run-time and handling the reaction kinetics of multiple interacting species in variably saturated subsurface systems. As UZF1 relies on a kinematic-wave approximation for unsaturated flow that neglects the diffusive terms in Richards equation, UZF-RT3D can be used for large-scale aquifer systems for which the UZF1 formulation is reasonable, that is, capillary-pressure gradients can be neglected and soil parameters can be treated as homogeneous. Decreased model run-time and the ability to include site-specific chemical species and chemical reactions make UZF-RT3D an attractive model for efficient simulation of multispecies reactive transport in variably saturated large-scale subsurface systems.

Simplified Discontinuous Galerkin Methods for Systems of Conservation Laws with Convex Extension

NASA Technical Reports Server (NTRS)

Barth, Timothy J.

1999-01-01

Simplified forms of the space-time discontinuous Galerkin (DG) and discontinuous Galerkin least-squares (DGLS) finite element method are developed and analyzed. The new formulations exploit simplifying properties of entropy endowed conservation law systems while retaining the favorable energy properties associated with symmetric variable formulations.

Specialty functions singularity mechanics problems

NASA Technical Reports Server (NTRS)

Sarigul, Nesrin

1989-01-01

The focus is in the development of more accurate and efficient advanced methods for solution of singular problems encountered in mechanics. At present, finite element methods in conjunction with special functions, boolean sum and blending interpolations are being considered. In dealing with systems which contain a singularity, special finite elements are being formulated to be used in singular regions. Further, special transition elements are being formulated to couple the special element to the mesh that models the rest of the system, and to be used in conjunction with 1-D, 2-D and 3-D elements within the same mesh. Computational simulation with a least squares fit is being utilized to construct special elements, if there is an unknown singularity in the system. A novel approach is taken in formulation of the elements in that: (1) the material properties are modified to include time, temperature, coordinate and stress dependant behavior within the element; (2) material properties vary at nodal points of the elements; (3) a hidden-symbolic computation scheme is developed and utilized in formulating the elements; and (4) special functions and boolean sum are utilized in order to interpolate the field variables and their derivatives along the boundary of the elements. It may be noted that the proposed methods are also applicable to fluids and coupled problems.

PLGA Biodegradable Nanoparticles Containing Perphenazine or Chlorpromazine Hydrochloride: Effect of Formulation and Release

PubMed Central

Halayqa, Mohammed; Domańska, Urszula

2014-01-01

In our study, poly(dl-lactide-co-glycolide) (PLGA) nanoparticles loaded with perphenazine (PPH) and chlorpromazine hydrochloride (CPZ-HCl) were formulated by emulsion solvent evaporation technique. The effect of various processing variables, including PLGA concentration, theoretical drug loading, poly(vinyl alcohol) (PVA) concentration and the power of sonication were assessed systematically to obtain higher encapsulation efficiency and to minimize the nanoparticles size. By the optimization formulation process, the nanoparticles were obtained in submicron size from 325.5 ± 32.4 to 374.3 ± 10.1 nm for nanoparticles loaded with PPH and CPZ-HCl, respectively. Nanoparticles observed by scanning electron microscopy (SEM) presented smooth surface and spherical shape. The encapsulation efficiency of nanoparticles loaded with PPH and CPZ-HCl were 83.9% and 71.0%, respectively. The drug loading were 51.1% and 39.4% for PPH and CPZ-HCl, respectively. Lyophilized nanoparticles with different PLGA concentration 0.8%, 1.3% and 1.6% (w/v) in formulation process were evaluated for in vitro release in phosphate buffered saline (pH = 7.4) by using dialysis bags. The release profile for both drugs have shown that the rate of PPH and CPZ-HCl release were dependent on a size and amount of drugs in the nanoparticles. PMID:25535080

PLGA biodegradable nanoparticles containing perphenazine or chlorpromazine hydrochloride: effect of formulation and release.

PubMed

Halayqa, Mohammed; Domańska, Urszula

2014-12-22

In our study, poly(dl-lactide-co-glycolide) (PLGA) nanoparticles loaded with perphenazine (PPH) and chlorpromazine hydrochloride (CPZ-HCl) were formulated by emulsion solvent evaporation technique. The effect of various processing variables, including PLGA concentration, theoretical drug loading, poly(vinyl alcohol) (PVA) concentration and the power of sonication were assessed systematically to obtain higher encapsulation efficiency and to minimize the nanoparticles size. By the optimization formulation process, the nanoparticles were obtained in submicron size from 325.5 ± 32.4 to 374.3 ± 10.1 nm for nanoparticles loaded with PPH and CPZ-HCl, respectively. Nanoparticles observed by scanning electron microscopy (SEM) presented smooth surface and spherical shape. The encapsulation efficiency of nanoparticles loaded with PPH and CPZ-HCl were 83.9% and 71.0%, respectively. The drug loading were 51.1% and 39.4% for PPH and CPZ-HCl, respectively. Lyophilized nanoparticles with different PLGA concentration 0.8%, 1.3% and 1.6% (w/v) in formulation process were evaluated for in vitro release in phosphate buffered saline (pH = 7.4) by using dialysis bags. The release profile for both drugs have shown that the rate of PPH and CPZ-HCl release were dependent on a size and amount of drugs in the nanoparticles.

Effect of Lactobacillus sporogenes on oral isoflavones bioavailability: single dose pharmacokinetic study in menopausal women.

PubMed

Benvenuti, Claudio; Setnikar, Ivo

2011-01-01

To verify the single dose bioavailability of two oral formulations of soy isoflavones, with and without lactobacilli, in menopausal women in antibiotic therapy. Twelve menopause women (mean age 54.3 years, BMI 25.0 kg/m2) participated in a controlled cross-over study. Reference and test treatments were: R = tablets containing soy isoflavones 60 mg (genistin 30 mg + daidzin 30 mg) + calcium and vitamin D3; E = R + 500 million vital spores of Lactobacillus sporogenes (E is Estromineral, a food supplement containing soy isoflavones 60 mg, calcium 141 mg and vitamin D3 5 microg). The design included 2 periods of 5 days of amoxicillin + clavulanate treatment with a 2-week wash-out. After each period alternatively a single dose of each formulation was given in randomised sequence. Genistein and daidzein were determined in plasma by HPLC, sampled 10 times within 24 h after dosing. Genistein pharmacokinetics parameters were higher after E than after R administration: peak plasma concentration (Cmax) +24.3%, area under the concentration curve (AUC0-24) +24.4% and mean residence time +11.0%. Daidzein Cmax and AUC showed a larger variability on R, evidenced by higher scatter from the mean on the formulation without lactobacilli. A trend is shown for a greater absorption of genistein from a formulation containing lactobacilli.

The use of D-optimal mixture design in optimising okara soap formulation for stratum corneum application.

PubMed

Borhan, Farrah Payyadhah; Abd Gani, Siti Salwa; Shamsuddin, Rosnah

2014-01-01

Okara, soybean waste from tofu and soymilk production, was utilised as a natural antioxidant in soap formulation for stratum corneum application. D-optimal mixture design was employed to investigate the influence of the main compositions of okara soap containing different fatty acid and oils (virgin coconut oil A (24-28% w/w), olive oil B (15-20% w/w), palm oil C (6-10% w/w), castor oil D (15-20% w/w), cocoa butter E (6-10% w/w), and okara F (2-7% w/w)) by saponification process on the response hardness of the soap. The experimental data were utilized to carry out analysis of variance (ANOVA) and to develop a polynomial regression model for okara soap hardness in terms of the six design factors considered in this study. Results revealed that the best mixture was the formulation that included 26.537% A, 19.999% B, 9.998% C, 16.241% D, 7.633% E, and 7.000% F. The results proved that the difference in the level of fatty acid and oils in the formulation significantly affects the hardness of soap. Depending on the desirable level of those six variables, creation of okara based soap with desirable properties better than those of commercial ones is possible.

Fidelity of the Integrated Force Method Solution

NASA Technical Reports Server (NTRS)

Hopkins, Dale; Halford, Gary; Coroneos, Rula; Patnaik, Surya

2002-01-01

The theory of strain compatibility of the solid mechanics discipline was incomplete since St. Venant's 'strain formulation' in 1876. We have addressed the compatibility condition both in the continuum and the discrete system. This has lead to the formulation of the Integrated Force Method. A dual Integrated Force Method with displacement as the primal variable has also been formulated. A modest finite element code (IFM/Analyzers) based on the IFM theory has been developed. For a set of standard test problems the IFM results were compared with the stiffness method solutions and the MSC/Nastran code. For the problems IFM outperformed the existing methods. Superior IFM performance is attributed to simultaneous compliance of equilibrium equation and compatibility condition. MSC/Nastran organization expressed reluctance to accept the high fidelity IFM solutions. This report discusses the solutions to the examples. No inaccuracy was detected in the IFM solutions. A stiffness method code with a small programming effort can be improved to reap the many IFM benefits when implemented with the IFMD elements. Dr. Halford conducted a peer-review on the Integrated Force Method. Reviewers' response is included.

Developing a modified preservative efficacy testing approach as a predictive tool for the evaluation of preservative systems in liquid home care products under variable test conditions.

PubMed

Hoyt, Anne L; Bushman, Don; Lewis, Nathan; Faber, Robert

2012-01-01

How can a formulator have confidence that a preservative system will perform as expected under adverse conditions? Extreme conditions that can lead to the development of "off odors" in the product can be a serious challenge for companies providing home care products in the global market. Formulation and stability testing occur under controlled parameters that simulate limited environmental conditions and microbial challenges are typically performed with a standard inoculum level. While this is an acceptable and dependable process, it does not necessarily assess how well a preservative system can perform under extreme environmental conditions or against unusually high levels of bacterial challenges. This is especially true when formulations are diluted and stored by the end-user. By modifying microbial challenge testing of a liquid dishwashing product to include unexpected dilution schemes, increased microbial assaults, and elevated temperatures, a pattern of preservative efficacy was established. The resulting approach proved to be a useful tool when developing use directions, recommended dilution levels, the overall surfactant system, preservative type, and storage restrictions.

PATTERN PREDICTION OF ACADEMIC SUCCESS.

ERIC Educational Resources Information Center

LUNNEBORG, CLIFFORD E.; LUNNEBORG, PATRICIA W.

A TECHNIQUE OF PATTERN ANALYSIS WHICH EMPHASIZES THE DEVELOPMENT OF MORE EFFECTIVE WAYS OF SCORING A GIVEN SET OF VARIABLES WAS FORMULATED. TO THE ORIGINAL VARIABLES WERE SUCCESSIVELY ADDED TWO, THREE, AND FOUR VARIABLE PATTERNS AND THE INCREASE IN PREDICTIVE EFFICIENCY ASSESSED. RANDOMLY SELECTED HIGH SCHOOL SENIORS WHO HAD PARTICIPATED IN THE…

Mathematical aspects of finite element methods for incompressible viscous flows

NASA Technical Reports Server (NTRS)

Gunzburger, M. D.

1986-01-01

Mathematical aspects of finite element methods are surveyed for incompressible viscous flows, concentrating on the steady primitive variable formulation. The discretization of a weak formulation of the Navier-Stokes equations are addressed, then the stability condition is considered, the satisfaction of which insures the stability of the approximation. Specific choices of finite element spaces for the velocity and pressure are then discussed. Finally, the connection between different weak formulations and a variety of boundary conditions is explored.

Use of nonlinear programming to optimize performance response to energy density in broiler feed formulation.

PubMed

Guevara, V R

2004-02-01

A nonlinear programming optimization model was developed to maximize margin over feed cost in broiler feed formulation and is described in this paper. The model identifies the optimal feed mix that maximizes profit margin. Optimum metabolizable energy level and performance were found by using Excel Solver nonlinear programming. Data from an energy density study with broilers were fitted to quadratic equations to express weight gain, feed consumption, and the objective function income over feed cost in terms of energy density. Nutrient:energy ratio constraints were transformed into equivalent linear constraints. National Research Council nutrient requirements and feeding program were used for examining changes in variables. The nonlinear programming feed formulation method was used to illustrate the effects of changes in different variables on the optimum energy density, performance, and profitability and was compared with conventional linear programming. To demonstrate the capabilities of the model, I determined the impact of variation in prices. Prices for broiler, corn, fish meal, and soybean meal were increased and decreased by 25%. Formulations were identical in all other respects. Energy density, margin, and diet cost changed compared with conventional linear programming formulation. This study suggests that nonlinear programming can be more useful than conventional linear programming to optimize performance response to energy density in broiler feed formulation because an energy level does not need to be set.

Using a constrained formulation based on probability summation to fit receiver operating characteristic (ROC) curves

NASA Astrophysics Data System (ADS)

Swensson, Richard G.; King, Jill L.; Good, Walter F.; Gur, David

2000-04-01

A constrained ROC formulation from probability summation is proposed for measuring observer performance in detecting abnormal findings on medical images. This assumes the observer's detection or rating decision on each image is determined by a latent variable that characterizes the specific finding (type and location) considered most likely to be a target abnormality. For positive cases, this 'maximum- suspicion' variable is assumed to be either the value for the actual target or for the most suspicious non-target finding, whichever is the greater (more suspicious). Unlike the usual ROC formulation, this constrained formulation guarantees a 'well-behaved' ROC curve that always equals or exceeds chance- level decisions and cannot exhibit an upward 'hook.' Its estimated parameters specify the accuracy for separating positive from negative cases, and they also predict accuracy in locating or identifying the actual abnormal findings. The present maximum-likelihood procedure (runs on PC with Windows 95 or NT) fits this constrained formulation to rating-ROC data using normal distributions with two free parameters. Fits of the conventional and constrained ROC formulations are compared for continuous and discrete-scale ratings of chest films in a variety of detection problems, both for localized lesions (nodules, rib fractures) and for diffuse abnormalities (interstitial disease, infiltrates or pnumothorax). The two fitted ROC curves are nearly identical unless the conventional ROC has an ill behaved 'hook,' below the constrained ROC.

How to Attain an Ultralow Interfacial Tension and a Three-Phase Behavior with a Surfactant Formulation for Enhanced Oil Recovery: A Review. Part 2. Performance Improvement Trends from Winsor's Premise to Currently Proposed Inter- and Intra-Molecular Mixtures.

PubMed

Salager, Jean-Louis; Forgiarini, Ana M; Márquez, Laura; Manchego, Lisbeth; Bullón, Johnny

2013-01-01

The minimum interfacial tension occurrence along a formulation scan at the so-called optimum formulation is discussed to be related to the interfacial curvature. The attained minimum tension is inversely proportional to the domain size of the bicontinuous microemulsion and to the interfacial layer rigidity, but no accurate prediction is available. The data from a very simple ternary system made of pure products accurately follows the correlation for optimum formulation, and exhibit a linear relationship between the performance index as the logarithm of the minimum tension at optimum, and the formulation variables. This relation is probably too simple when the number of variables is increased as in practical cases. The review of published data for more realistic systems proposed for enhanced oil recovery over the past 30 years indicates a general guidelines following Winsor's basic studies concerning the surfactant-oil-water interfacial interactions. It is well known that the major performance benefits are achieved by blending amphiphilic species at the interface as intermolecular or intramolecular mixtures, sometimes in extremely complex formulations. The complexity is such that a good knowledge of the possible trends and an experienced practical know-how to avoid trial and error are important for the practitioner in enhanced oil recovery.

Drug delivery strategies for poorly water-soluble drugs.

PubMed

Fahr, Alfred; Liu, Xiangli

2007-07-01

The drug candidates coming from combinatorial chemistry research and/or the drugs selected from biologically based high-throughput screening are quite often very lipophilic, as these drug candidates exert their pharmacological action at or in biological membranes or membrane-associated proteins. This challenges drug delivery institutions in industry or academia to develop carrier systems for the optimal oral and parenteral administration of these drugs. To mention only a few of the challenges for this class of drugs: their oral bioavailability is poor and highly variable, and carrier development for parenteral administration is faced with problems, including the massive use of surface-active excipients for solubilisation. Formulation specialists are confronted with an even higher level of difficulties when these drugs have to be delivered site specifically. This article addresses the emerging formulation designs for delivering of poorly water-soluble drugs.

Development of a Vorticity-Velocity Navier-Stokes Formulation for the Study of Compressibility Effects on Dynamic Stall

NASA Technical Reports Server (NTRS)

Ghia, K. N.; Ghia, U.

1996-01-01

The first major area of this study was to develop a vorticity-velocity formulation and numerical solution algorithms suitable for the analyses of incompressible as well as low-to- moderate-speed compressible flows. Research performed towards contributing to the determination of the appropriate vorticity and dilation creation boundary conditions suggested to temporarily set aside this approach and use a primitive-variable approach other than the pseudo-compressibility approach used. The second major area of study was initiated to comprehensively examine the INS-2D and INS-3D programs from the point of view of boundary conditions. The research carried out was documented in the form of two technical papers which are included in Appendices A and B; the boundary-condition related issues for INS-3D are briefly mentioned.

The role of modern control theory in the design of controls for aircraft turbine engines

NASA Technical Reports Server (NTRS)

Zeller, J.; Lehtinen, B.; Merrill, W.

1982-01-01

The development, applications, and current research in modern control theory (MCT) are reviewed, noting the importance for fuel-efficient operation of turbines with variable inlet guide vanes, compressor stators, and exhaust nozzle area. The evolution of multivariable propulsion control design is examined, noting a basis in a matrix formulation of the differential equations defining the process, leading to state space formulations. Reports and papers which appeared from 1970-1982 which dealt with problems in MCT applications to turbine engine control design are outlined, including works on linear quadratic regulator methods, frequency domain methods, identification, estimation, and model reduction, detection, isolation, and accommodation, and state space control, adaptive control, and optimization approaches. Finally, NASA programs in frequency domain design, sensor failure detection, computer-aided control design, and plant modeling are explored

Optimal slew path planning for the Sino-French Space-based multiband astronomical Variable Objects Monitor mission

NASA Astrophysics Data System (ADS)

She, Yuchen; Li, Shuang

2018-01-01

The planning algorithm to calculate a satellite's optimal slew trajectory with a given keep-out constraint is proposed. An energy-optimal formulation is proposed for the Space-based multiband astronomical Variable Objects Monitor Mission Analysis and Planning (MAP) system. The innovative point of the proposed planning algorithm lies in that the satellite structure and control limitation are not considered as optimization constraints but are formulated into the cost function. This modification is able to relieve the burden of the optimizer and increases the optimization efficiency, which is the major challenge for designing the MAP system. Mathematical analysis is given to prove that there is a proportional mapping between the formulation and the satellite controller output. Simulations with different scenarios are given to demonstrate the efficiency of the developed algorithm.

An Interface Damage Model for the Simulation of Delamination Under Variable-Mode Ratio in Composite Materials

NASA Technical Reports Server (NTRS)

Turon, Albert; Camanho, Pedro P.; Costa, Josep; Davila, Carlos G.

2004-01-01

A thermodynamically consistent damage model for the simulation of progressive delamination under variable mode ratio is presented. The model is formulated in the context of the Damage Mechanics (DM). The constitutive equations that result from the variation of the free energy with damage are used to model the initiation and propagation of delamination. A new delamination initiation criterion is developed to assure that the formulation can account for changes in the loading mode in a thermodynamically consistent way. Interfacial penetration of two adjacent layers after complete decohesion is prevented by the formulation of the free energy. The model is implemented into the commercial finite element code ABAQUS by means of a user-written decohesion element. Finally, the numerical predictions given by the model are compared with experimental results.

Bioequivalence of two lansoprazole delayed release capsules 30 mg in healthy male volunteers under fasting, fed and fasting-applesauce conditions: a partial replicate crossover study design to estimate the pharmacokinetics of highly variable drugs.

PubMed

Thota, S; Khan, S M; Tippabhotla, S K; Battula, R; Gadiko, C; Vobalaboina, V

2013-11-01

An open-label, 2-treatment, 3-sequence, 3-period, single-dose, partial replicate crossover studies under fasting (n=48), fed (n=60) and fasting-applesauce (n=48) (sprinkled on one table spoonful of applesauce) modalities were conducted in healthy adult male volunteers to evaluate bioequivalence between 2 formulations of lansoprazole delayed release capsules 30 mg. In all the 3 studies, as per randomization, either test or reference formulations were administered in a crossover manner with a required washout period of at least 7 days. Blood samples were collected adequately (0-24 h) to determine lansoprazole plasma concentrations using a validated LC-MS/MS analytical method. To characterize the pharmacokinetic parameters (Cmax, AUC0-t, AUC0-∞, Tmax, Kel and T1/2) of lansoprazole, non-compartmental analysis and ANOVA was applied on ln-transformed values. The bioequivalence was tested based on within-subject variability of the reference formulation. In fasting and fed studies (within-subject variability>30%) bioequivalence was evaluated with scaled average bioequivalence, hence for the pharmacokinetic parameters Cmax, AUC0-t and AUC0-∞, the 95% upper confidence bound for (μT-μR)2-θσ2 WR was ≤0, and the point estimates (test-to-reference ratio) were within the regulatory acceptance limit 80.00-125.00%. In fasting-applesauce study (within-subject variability<30%) bioequivalence was evaluated with average bioequivalence, the 90% CI of ln-transformed data of Cmax, AUC0-t and AUC0-∞ were within the regulatory acceptance limit 80.00-125.00%. Based on these aforesaid statistical inferences, it was concluded that the test formulation is bioequivalent to reference formulation. © Georg Thieme Verlag KG Stuttgart · New York.

Variational approach to the volume viscosity of fluids

NASA Astrophysics Data System (ADS)

Zuckerwar, Allan J.; Ash, Robert L.

2006-04-01

The variational principle of Hamilton is applied to develop an analytical formulation to describe the volume viscosity in fluids. The procedure described here differs from those used in the past in that a dissipative process is represented by the chemical affinity and progress variable (sometimes called "order parameter") of a reacting species. These state variables appear in the variational integral in two places: first, in the expression for the internal energy, and second, in a subsidiary condition accounting for the conservation of the reacting species. As a result of the variational procedure, two dissipative terms appear in the Navier-Stokes equation. The first is the traditional volume viscosity term, proportional to the dilatational component of velocity; the second term is proportional to the material time derivative of the pressure gradient. Values of the respective volume viscosity coefficients are determined by applying the resulting volume-viscous Navier-Stokes equation to the case of acoustical propagation and then comparing expressions for the dispersion and absorption of sound. The formulation includes the special case of equilibration of the translational degrees of freedom. As examples, values are tabulated for dry and humid air, argon, and sea water.

Stage-by-Stage and Parallel Flow Path Compressor Modeling for a Variable Cycle Engine, NASA Advanced Air Vehicles Program - Commercial Supersonic Technology Project - AeroServoElasticity

NASA Technical Reports Server (NTRS)

Kopasakis, George; Connolly, Joseph W.; Cheng, Larry

2015-01-01

This paper covers the development of stage-by-stage and parallel flow path compressor modeling approaches for a Variable Cycle Engine. The stage-by-stage compressor modeling approach is an extension of a technique for lumped volume dynamics and performance characteristic modeling. It was developed to improve the accuracy of axial compressor dynamics over lumped volume dynamics modeling. The stage-by-stage compressor model presented here is formulated into a parallel flow path model that includes both axial and rotational dynamics. This is done to enable the study of compressor and propulsion system dynamic performance under flow distortion conditions. The approaches utilized here are generic and should be applicable for the modeling of any axial flow compressor design accurate time domain simulations. The objective of this work is as follows. Given the parameters describing the conditions of atmospheric disturbances, and utilizing the derived formulations, directly compute the transfer function poles and zeros describing these disturbances for acoustic velocity, temperature, pressure, and density. Time domain simulations of representative atmospheric turbulence can then be developed by utilizing these computed transfer functions together with the disturbance frequencies of interest.

Multi-sensor Cloud Retrieval Simulator and Remote Sensing from Model Parameters . Pt. 1; Synthetic Sensor Radiance Formulation; [Synthetic Sensor Radiance Formulation

NASA Technical Reports Server (NTRS)

Wind, G.; DaSilva, A. M.; Norris, P. M.; Platnick, S.

2013-01-01

In this paper we describe a general procedure for calculating synthetic sensor radiances from variable output from a global atmospheric forecast model. In order to take proper account of the discrepancies between model resolution and sensor footprint, the algorithm takes explicit account of the model subgrid variability, in particular its description of the probability density function of total water (vapor and cloud condensate.) The simulated sensor radiances are then substituted into an operational remote sensing algorithm processing chain to produce a variety of remote sensing products that would normally be produced from actual sensor output. This output can then be used for a wide variety of purposes such as model parameter verification, remote sensing algorithm validation, testing of new retrieval methods and future sensor studies.We show a specific implementation using the GEOS-5 model, the MODIS instrument and the MODIS Adaptive Processing System (MODAPS) Data Collection 5.1 operational remote sensing cloud algorithm processing chain (including the cloud mask, cloud top properties and cloud optical and microphysical properties products). We focus on clouds because they are very important to model development and improvement.

Optimisation of spray-drying process variables for dry powder inhalation (DPI) formulations of corticosteroid/cyclodextrin inclusion complexes.

PubMed

Cabral-Marques, Helena; Almeida, Rita

2009-09-01

This study aims to develop and characterise a beclomethasone diproprionate:gamma-cyclodextrin (BDP:gamma-CYD) complex and to optimise the variables on the spray-drying process, in order to obtain a powder with the most suitable characteristics for lung delivery. The spray-dried powder--in a mass ratio of 2:5 (BDP:gamma-CYD)--was physically mixed with three carriers of different particle sizes and in different ratios. Particle-size distribution, shape and morphology, moisture content, and uniformity in BDP content of formulations were studied. In vitro aerolisation behaviour of the formulations was evaluated using the Rotahaler, and the performance was characterised based on the uniformity of emitted dose and aerodynamic particle-size distribution (respirable fraction (RF), as a percentage of nominal dose (RFN) and emitted dose (RFE)). The most suitable conditions for the preparation of BDP:gamma-CYD complexes were obtained with the solution flow of 5 ml/min, T(in) of 70 degrees C and T(out) of 50 degrees C. Statistically significant differences in the aerodynamic performances were obtained for formulations containing BDP:gamma-CYD complexes prepared using different solution flows and different T(in) (p<0.05). RFN and RFE vary in direct proportion with T(in), while an inverse relationship was observed for the solution flow. A direct correlation between the RFE and the T(out) was identified. Performance of the formulations was compared with an established commercial product (Beclotaide Rotacaps 100 microg) with improved performance of RF: formulations with respitose carrier attained RFN and RFE twofold greater, and formulations based on 63-90 microm fraction lactose and trehalose achieved a threefold improvement; also, all formulations showed that the percentage of dose of BDP deposited in the "oropharynx" compartment was reduced to half.

Hamilton's Equations with Euler Parameters for Rigid Body Dynamics Modeling. Chapter 3

NASA Technical Reports Server (NTRS)

Shivarama, Ravishankar; Fahrenthold, Eric P.

2004-01-01

A combination of Euler parameter kinematics and Hamiltonian mechanics provides a rigid body dynamics model well suited for use in strongly nonlinear problems involving arbitrarily large rotations. The model is unconstrained, free of singularities, includes a general potential energy function and a minimum set of momentum variables, and takes an explicit state space form convenient for numerical implementation. The general formulation may be specialized to address particular applications, as illustrated in several three dimensional example problems.

Optimization and formulation design of gels of Diclofenac and Curcumin for transdermal drug delivery by Box-Behnken statistical design.

PubMed

Chaudhary, Hema; Kohli, Kanchan; Amin, Saima; Rathee, Permender; Kumar, Vikash

2011-02-01

The aim of this study was to develop and optimize a transdermal gel formulation for Diclofenac diethylamine (DDEA) and Curcumin (CRM). A 3-factor, 3-level Box-Behnken design was used to derive a second-order polynomial equation to construct contour plots for prediction of responses. Independent variables studied were the polymer concentration (X(1)), ethanol (X(2)) and propylene glycol (X(3)) and the levels of each factor were low, medium, and high. The dependent variables studied were the skin permeation rate of DDEA (Y(1)), skin permeation rate of CRM (Y(2)), and viscosity of the gels (Y(3)). Response surface plots were drawn, statistical validity of the polynomials was established to find the compositions of optimized formulation which was evaluated using the Franz-type diffusion cell. The permeation rate of DDEA increased proportionally with ethanol concentration but decreased with polymer concentration, whereas the permeation rate of CRM increased proportionally with polymer concentration. Gels showed a non-Fickian super case II (typical zero order) and non-Fickian diffusion release mechanism for DDEA and CRM, respectively. The design demonstrated the role of the derived polynomial equation and contour plots in predicting the values of dependent variables for the preparation and optimization of gel formulation for transdermal drug release. Copyright © 2010 Wiley-Liss, Inc.

Design and Optimization of Floating Drug Delivery System of Acyclovir

PubMed Central

Kharia, A. A.; Hiremath, S. N.; Singhai, A. K.; Omray, L. K.; Jain, S. K.

2010-01-01

The purpose of the present work was to design and optimize floating drug delivery systems of acyclovir using psyllium husk and hydroxypropylmethylcellulose K4M as the polymers and sodium bicarbonate as a gas generating agent. The tablets were prepared by wet granulation method. A 32 full factorial design was used for optimization of drug release profile. The amount of psyllium husk (X1) and hydroxypropylmethylcellulose K4M (X2) were selected as independent variables. The times required for 50% (t50%) and 70% (t70%) drug dissolution were selected as dependent variables. All the designed nine batches of formulations were evaluated for hardness, friability, weight variation, drug content uniformity, swelling index, in vitro buoyancy, and in vitro drug release profile. All formulations had floating lag time below 3 min and constantly floated on dissolution medium for more than 24 h. Validity of the developed polynomial equation was verified by designing two check point formulations (C1 and C2). The closeness of predicted and observed values for t50% and t70% indicates validity of derived equations for the dependent variables. These studies indicated that the proper balance between psyllium husk and hydroxypropylmethylcellulose K4M can produce a drug dissolution profile similar to the predicted dissolution profile. The optimized formulations followed Higuchi's kinetics while the drug release mechanism was found to be anomalous type, controlled by diffusion through the swollen matrix. PMID:21694992

Design and optimization of floating drug delivery system of acyclovir.

PubMed

Kharia, A A; Hiremath, S N; Singhai, A K; Omray, L K; Jain, S K

2010-09-01

The purpose of the present work was to design and optimize floating drug delivery systems of acyclovir using psyllium husk and hydroxypropylmethylcellulose K4M as the polymers and sodium bicarbonate as a gas generating agent. The tablets were prepared by wet granulation method. A 3(2) full factorial design was used for optimization of drug release profile. The amount of psyllium husk (X1) and hydroxypropylmethylcellulose K4M (X2) were selected as independent variables. The times required for 50% (t(50%)) and 70% (t(70%)) drug dissolution were selected as dependent variables. All the designed nine batches of formulations were evaluated for hardness, friability, weight variation, drug content uniformity, swelling index, in vitro buoyancy, and in vitro drug release profile. All formulations had floating lag time below 3 min and constantly floated on dissolution medium for more than 24 h. Validity of the developed polynomial equation was verified by designing two check point formulations (C1 and C2). The closeness of predicted and observed values for t(50%) and t(70%) indicates validity of derived equations for the dependent variables. These studies indicated that the proper balance between psyllium husk and hydroxypropylmethylcellulose K4M can produce a drug dissolution profile similar to the predicted dissolution profile. The optimized formulations followed Higuchi's kinetics while the drug release mechanism was found to be anomalous type, controlled by diffusion through the swollen matrix.

How do formulation and process parameters impact blend and unit dose uniformity? Further analysis of the product quality research institute blend uniformity working group industry survey.

PubMed

Hancock, Bruno C; Garcia-Munoz, Salvador

2013-03-01

Responses from the second Product Quality Research Institute (PQRI) Blend Uniformity Working Group (BUWG) survey of industry have been reanalyzed to identify potential links between formulation and processing variables and the measured uniformity of blends and unit dosage forms. As expected, the variability of the blend potency and tablet potency data increased with a decrease in the loading of the active pharmaceutical ingredient (API). There was also an inverse relationship between the nominal strength of the unit dose and the blend uniformity data. The data from the PQRI industry survey do not support the commonly held viewpoint that granulation processes are necessary to create and sustain tablet and capsule formulations with a high degree of API uniformity. There was no correlation between the blend or tablet potency variability and the type of process used to manufacture the product. Although it is commonly believed that direct compression processes should be avoided for low API loading formulations because of blend and tablet content uniformity concerns, the data for direct compression processes reported by the respondents to the PQRI survey suggest that such processes are being used routinely to manufacture solid dosage forms of acceptable quality even when the drug loading is quite low. Copyright © 2012 Wiley Periodicals, Inc.

Enhanced Solubility and Dissolution Rate of Lacidipine Nanosuspension: Formulation Via Antisolvent Sonoprecipitation Technique and Optimization Using Box-Behnken Design.

PubMed

Kassem, Mohamed A A; ElMeshad, Aliaa N; Fares, Ahmed R

2017-05-01

Lacidipine (LCDP) is a highly lipophilic calcium channel blocker of poor aqueous solubility leading to poor oral absorption. This study aims to prepare and optimize LCDP nanosuspensions using antisolvent sonoprecipitation technique to enhance the solubility and dissolution of LCDP. A three-factor, three-level Box-Behnken design was employed to optimize the formulation variables to obtain LCDP nanosuspension of small and uniform particle size. Formulation variables were as follows: stabilizer to drug ratio (A), sodium deoxycholate percentage (B), and sonication time (C). LCDP nanosuspensions were assessed for particle size, zeta potential, and polydispersity index. The formula with the highest desirability (0.969) was chosen as the optimized formula. The values of the formulation variables (A, B, and C) in the optimized nanosuspension were 1.5, 100%, and 8 min, respectively. Optimal LCDP nanosuspension had particle size (PS) of 273.21 nm, zeta potential (ZP) of -32.68 mV and polydispersity index (PDI) of 0.098. LCDP nanosuspension was characterized using x-ray powder diffraction, differential scanning calorimetry, and transmission electron microscopy. LCDP nanosuspension showed saturation solubility 70 times that of raw LCDP in addition to significantly enhanced dissolution rate due to particle size reduction and decreased crystallinity. These results suggest that the optimized LCDP nanosuspension could be promising to improve oral absorption of LCDP.

Detection of drug active ingredients by chemometric processing of solid-state NMR spectrometry data -- the case of acetaminophen.

PubMed

Paradowska, Katarzyna; Jamróz, Marta Katarzyna; Kobyłka, Mariola; Gowin, Ewelina; Maczka, Paulina; Skibiński, Robert; Komsta, Łukasz

2012-01-01

This paper presents a preliminary study in building discriminant models from solid-state NMR spectrometry data to detect the presence of acetaminophen in over-the-counter pharmaceutical formulations. The dataset, containing 11 spectra of pure substances and 21 spectra of various formulations, was processed by partial least squares discriminant analysis (PLS-DA). The model found coped with the discrimination, and its quality parameters were acceptable. It was found that standard normal variate preprocessing had almost no influence on unsupervised investigation of the dataset. The influence of variable selection with the uninformative variable elimination by PLS method was studied, reducing the dataset from 7601 variables to around 300 informative variables, but not improving the model performance. The results showed the possibility to construct well-working PLS-DA models from such small datasets without a full experimental design.

Real-time fuzzy inference based robot path planning

NASA Technical Reports Server (NTRS)

Pacini, Peter J.; Teichrow, Jon S.

1990-01-01

This project addresses the problem of adaptive trajectory generation for a robot arm. Conventional trajectory generation involves computing a path in real time to minimize a performance measure such as expended energy. This method can be computationally intensive, and it may yield poor results if the trajectory is weakly constrained. Typically some implicit constraints are known, but cannot be encoded analytically. The alternative approach used here is to formulate domain-specific knowledge, including implicit and ill-defined constraints, in terms of fuzzy rules. These rules utilize linguistic terms to relate input variables to output variables. Since the fuzzy rulebase is determined off-line, only high-level, computationally light processing is required in real time. Potential applications for adaptive trajectory generation include missile guidance and various sophisticated robot control tasks, such as automotive assembly, high speed electrical parts insertion, stepper alignment, and motion control for high speed parcel transfer systems.

The Vocational Significance of Black Identity: Cultural Formulation Approach to Career Assessment and Career Counseling

ERIC Educational Resources Information Center

Byars-Winston, Angela

2010-01-01

Scholarship is emerging on intervention models that purposefully attend to cultural variables throughout the career assessment and career counseling process. One heuristic model that offers promise to advance culturally relevant vocational practice with African Americans is the Outline for Cultural Formulation (CF). This article explicates the…

Improved ant colony optimization for optimal crop and irrigation water allocation by incorporating domain knowledge

USDA-ARS?s Scientific Manuscript database

An improved ant colony optimization (ACO) formulation for the allocation of crops and water to different irrigation areas is developed. The formulation enables dynamic adjustment of decision variable options and makes use of visibility factors (VFs, the domain knowledge that can be used to identify ...

Optimizing habitat location for black-tailed prairie dogs in southwestern South Dakota

Treesearch

John Hof; Michael Bevers; Daniel W. Uresk; Gregory L. Schenbeck

2002-01-01

A spatial optimization model was formulated and used to maximize black-tailed prairie dog populations in the Badlands National Park and the Buffalo Gap National Grassland in South Dakota. The choice variables involved the strategic placement of limited additional protected habitat. Population dynamics were captured in formulations that reflected exponential population...

Current advances on polynomial resultant formulations

NASA Astrophysics Data System (ADS)

Sulaiman, Surajo; Aris, Nor'aini; Ahmad, Shamsatun Nahar

2017-08-01

Availability of computer algebra systems (CAS) lead to the resurrection of the resultant method for eliminating one or more variables from the polynomials system. The resultant matrix method has advantages over the Groebner basis and Ritt-Wu method due to their high complexity and storage requirement. This paper focuses on the current resultant matrix formulations and investigates their ability or otherwise towards producing optimal resultant matrices. A determinantal formula that gives exact resultant or a formulation that can minimize the presence of extraneous factors in the resultant formulation is often sought for when certain conditions that it exists can be determined. We present some applications of elimination theory via resultant formulations and examples are given to explain each of the presented settings.

Controlling Release of Integral Lipid Nanoparticles Based on Osmotic Pump Technology.

PubMed

Tian, Zhiqiang; Yu, Qin; Xie, Yunchang; Li, Fengqian; Lu, Yi; Dong, Xiaochun; Zhao, Weili; Qi, Jianping; Wu, Wei

2016-08-01

To achieve controlled release of integral nanoparticles by the osmotic pump strategy using nanostructured lipid carriers (NLCs) as model nanoparticles. NLCs was prepared by a hot-homogenization method, transformed into powder by lyophilization, and formulated into osmotic pump tablets (OPTs). Release of integral NLCs was visualized by live imaging after labeling with a water-quenching fluorescent probe. Effects of formulation variables on in vitro release characteristics were evaluated by measuring the model drug fenofibrate. Pharmacokinetics were studied in beagle dogs using the core tablet and a micronized fenofibrate formulation as references. NLCs are released through the release orifices of the OPTs as integral nanoparticles. Near zero-order kinetics can be achieved by optimizing the influencing variables. After oral administration, decreased C max and steady drug levels for as long as over 24 h are observed. NLC-OPTs show an oral bioavailability of the model drug fenofibrate similar to that of the core tablets, which is about 1.75 folds that of a fast-release formulation. Controlled release of integral NLCs is achieved by the osmotic pump strategy.

Remarks on the "Non-canonicity Puzzle": Lagrangian Symmetries of the Einstein-Hilbert Action

NASA Astrophysics Data System (ADS)

Kiriushcheva, N.; Komorowski, P. G.; Kuzmin, S. V.

2012-07-01

Given the non-canonical relationship between variables used in the Hamiltonian formulations of the Einstein-Hilbert action (due to Pirani, Schild, Skinner (PSS) and Dirac) and the Arnowitt-Deser-Misner (ADM) action, and the consequent difference in the gauge transformations generated by the first-class constraints of these two formulations, the assumption that the Lagrangians from which they were derived are equivalent leads to an apparent contradiction that has been called "the non-canonicity puzzle". In this work we shall investigate the group properties of two symmetries derived for the Einstein-Hilbert action: diffeomorphism, which follows from the PSS and Dirac formulations, and the one that arises from the ADM formulation. We demonstrate that unlike the diffeomorphism transformations, the ADM transformations (as well as others, which can be constructed for the Einstein-Hilbert Lagrangian using Noether's identities) do not form a group. This makes diffeomorphism transformations unique (the term "canonical" symmetry might be suggested). If the two Lagrangians are to be called equivalent, canonical symmetry must be preserved. The interplay between general covariance and the canonicity of the variables used is discussed.

Formulation and Optimization of Multiparticulate Drug Delivery System Approach for High Drug Loading.

PubMed

Shah, Neha; Mehta, Tejal; Gohel, Mukesh

2017-08-01

The aim of the present work was to develop and optimize multiparticulate formulation viz. pellets of naproxen by employing QbD and risk assessment approach. Mixture design with extreme vertices was applied to the formulation with high loading of drug (about 90%) and extrusion-spheronization as a process for manufacturing pellets. Independent variables chosen were level of microcrystalline cellulose (MCC)-X 1 , polyvinylpyrrolidone K-90 (PVP K-90)-X 2 , croscarmellose sodium (CCS)-X 3 , and polacrilin potassium (PP)-X 4 . Dependent variables considered were disintegration time (DT)-Y 1 , sphericity-Y 2 , and percent drug release-Y 3 . The formulation was optimized based on the batches generated by MiniTab 17 software. The batch with maximum composite desirability (0.98) proved to be optimum. From the evaluation of design batches, it was observed that, even in low variation, the excipients affect the pelletization property of the blend and also the final drug release. In conclusion, pellets with high drug loading can be effectively manufactured and optimized systematically using QbD approach.

Preparation of finasteride capsules-loaded drug nanoparticles: formulation, optimization, in vitro, and pharmacokinetic evaluation

PubMed Central

Ahmed, Tarek A

2016-01-01

In this study, optimized freeze-dried finasteride nanoparticles (NPs) were prepared from drug nanosuspension formulation that was developed using the bottom–up technique. The effects of four formulation and processing variables that affect the particle size and solubility enhancement of the NPs were explored using the response surface optimization design. The optimized formulation was morphologically characterized using transmission electron microscopy (TEM). Physicochemical interaction among the studied components was investigated. Crystalline change was investigated using X-ray powder diffraction (XRPD). Crystal growth of the freeze-dried NPs was compared to the corresponding aqueous drug nanosuspension. Freeze-dried NPs formulation was subsequently loaded into hard gelatin capsules that were examined for in vitro dissolution and pharmacokinetic behavior. Results revealed that in most of the studied variables, some of the quadratic and interaction effects had a significant effect on the studied responses. TEM image illustrated homogeneity and shape of the prepared NPs. No interaction among components was noticed. XRPD confirmed crystalline state change in the optimized NPs. An enhancement in the dissolution rate of more than 2.5 times from capsules filled with optimum drug NPs, when compared to capsules filled with pure drug, was obtained. Crystal growth, due to Ostwald ripening phenomenon and positive Gibbs free energy, was reduced following lyophilization of the nanosuspension formulation. Pharmacokinetic parameters from drug NPs were superior to that of pure drug and drug microparticles. In conclusion, freeze-dried NPs based on drug nanosuspension formulation is a successful technique in enhancing stability, solubility, and in vitro dissolution of poorly water-soluble drugs with possible impact on the drug bioavailability. PMID:26893559

A logical approach to optimize the nanostructured lipid carrier system of irinotecan: efficient hybrid design methodology

NASA Astrophysics Data System (ADS)

Mohan Negi, Lalit; Jaggi, Manu; Talegaonkar, Sushama

2013-01-01

Development of an effective formulation involves careful optimization of a number of excipient and process variables. Sometimes the number of variables is so large that even the most efficient optimization designs require a very large number of trials which put stress on costs as well as time. A creative combination of a number of design methods leads to a smaller number of trials. This study was aimed at the development of nanostructured lipid carriers (NLCs) by using a combination of different optimization methods. A total of 11 variables were first screened using the Plackett-Burman design for their effects on formulation characteristics like size and entrapment efficiency. Four out of 11 variables were found to have insignificant effects on the formulation parameters and hence were screened out. Out of the remaining seven variables, four (concentration of tween-80, lecithin, sodium taurocholate, and total lipid) were found to have significant effects on the size of the particles while the other three (phase ratio, drug to lipid ratio, and sonication time) had a higher influence on the entrapment efficiency. The first four variables were optimized for their effect on size using the Taguchi L9 orthogonal array. The optimized values of the surfactants and lipids were kept constant for the next stage, where the sonication time, phase ratio, and drug:lipid ratio were varied using the Box-Behnken design response surface method to optimize the entrapment efficiency. Finally, by performing only 38 trials, we have optimized 11 variables for the development of NLCs with a size of 143.52 ± 1.2 nm, zeta potential of -32.6 ± 0.54 mV, and 98.22 ± 2.06% entrapment efficiency.

A Many-Objective Approach to Developing Adaptive Water Supply Portfolios in the 'Research Triangle' Region of North Carolina

NASA Astrophysics Data System (ADS)

Zeff, H. B.; Kasprzyk, J. R.; Reed, P. M.; Characklis, G. W.

2012-12-01

This study uses many-objective evolutionary optimization to quantify the tradeoffs water utilities face when developing flexible water shortage response plans. Alternatives to infrastructure development, such as temporary demand management programs and inter-utility water transfer agreements, allow local water providers to develop portfolios of water supply options capable of adapting to changing hydrologic conditions and growing water demand. The extent to which these options are implemented will be determined by a number of conflicting operational and financial considerations. An integrated reservoir simulation model including four large water utilities in the 'Research Triangle' region of North Carolina is used to evaluate the potential tradeoffs resulting from regional demands on shared infrastructure, customer concerns, and the financial uncertainty caused by the intermittent and irregular nature of drought. Instead of providing one optimal solution, multi-objective evolutionary algorithms (MOEAs) use the concept of non-dominations to discover a set of portfolio options in which no solution is inferior to any other solution in all objectives. Interactive visual analytics enable water providers to explore these tradeoffs and develop water shortage response plans tailored to their individual circumstances. The simulation model is evaluated under a number of different formulations to help identify and visualize the impacts of water efficiency, revenue/cost variability, consumer effects, and inter-utility cooperation. The different problems are formulated by adding portfolio options and objectives in such a way that the lower dimensional problem formulations are sub-sets of the full formulation. The full formulation considers reservoir reliability, water use restriction frequency, total water transfer allotment, total costs, revenue/cost variability, and additional consumer losses during restrictions. The simulation results highlight the inadequacy of lower order, cost-benefit type analyses to evaluate water management techniques as they move beyond the construction of large storage infrastructure. This work can help water providers develop the analytical tools to evaluate complex, adaptive techniques that are becoming more attractive in an era of growing municipal demand, risking infrastructure costs, and uncertain hydrology.

Assessing bioequivalence of generic modified-release antiepileptic drugs

PubMed Central

Chang, Yi-Ting; Davit, Barbara; Gidal, Barry E.; Krauss, Gregory L.

2016-01-01

Objectives: The purpose of this study was to determine how closely generic modified-release antiepileptic drugs (MR-AEDs) resemble reference (brand) formulations by comparing peak concentrations (Cmax), total absorption (area under the curve [AUC]), time to Cmax (Tmax), intersubject variability, and food effects between generic and reference products. Methods: We tabulated Cmax and AUC data from the bioequivalence (BE) studies used to support the approvals of generic Food and Drug Administration–approved MR-AEDs. We compared differences in 90% confidence intervals of the generic/reference AUC and Cmax geometric mean ratios, and intersubject variability, Tmax and delivery profiles and food effects. Results: Forty-two MR-AED formulations were studied in 3,175 healthy participants without epilepsy in 97 BE studies. BE ratios for AUC and Cmax were similar between most generic and reference products: AUC ratios varied by >15% in 11.4% of BE studies; Cmax varied by >15% in 25.8% of studies. Tmax was more variable, with >30% difference in 13 studies (usually delayed in the fed compared to fasting BE studies). Generic and reference MR products had similar intersubject variability. Immediate-release AEDs showed less intersubject variability in AUC than did MR-AEDs. Conclusions: Most generic and reference MR-AEDs have similar AUC and Cmax values. Ratios for some products, however, are near acceptance limits and Tmax values may vary. Food effects are common with MR-AED products. High variability in pharmacokinetic values for once-a-day MR-AEDs suggests their major advantage compared to immediate-release AED formulations may be the convenience of less frequent dosing to improve adherence. PMID:27016518

On the formulation and solution of an emergency routing problem.

DOT National Transportation Integrated Search

2007-10-01

In this work, we will identify important variables that contribute to : vehicular movement in an emergency environment. In particular, we for- : mulate and pose the Convoy Routing Problem (using far fewer variables : than other important models witho...

The Vocational Significance of Black Identity: Cultural Formulation Approach to Career Assessment and Career Counseling

PubMed Central

Byars-Winston, Angela M.

2010-01-01

Scholarship is emerging on intervention models that purposefully attend to cultural variables throughout the career assessment and career counseling process (Swanson & Fouad, in press). One heuristic model that offers promise to advance culturally-relevant vocational practice with African Americans is the Outline for Cultural Formulation (American Psychiatric Association, 1994). This article explicates the Outline for Cultural Formulation in career assessment and career counseling with African Americans integrating the concept of cultural identity into the entire model. The article concludes with an illustration of the Outline for Cultural Formulation model with an African American career client. PMID:20495668

Formulation effects on the mechanical and release properties of metronidazole suppositories.

PubMed

Adegboye, T A; Itiola, O A

2003-09-01

A study of the effects of Tween 20 and Tween 80 non-ionic surfactants, and witepsol H15 and polyethylene glycol (PEG) 2850 bases, on the mechanical and release properties of metronidazole suppositories was made. Mechanical strength was assessed by breaking strength values F. The values of F increased with increase in concentration of surfactant. The values of F for formulations containing Tween 20 were higher than those obtained for formulations containing Tween 80. Witepsol bases gave higher values of F than corresponding PEG bases. Release characteristics were assessed by the time for 80% drug release (t80), values of dissolution rate constants, k1 and k2 and the time of intersection, t1. The values of t80 decreased while those of k1 and k2 increased with increase in surfactant concentration. The values of t80 were lower, while those of k1 and k2 were higher, for formulations containing Tween 20 than for those formulations containing Tween 80. Witepsol bases gave lower t80 values and higher k1 and k2 values than their corresponding PEG bases. The concentration of surfactant, C, had the largest individual effect on the mechanical and release parameters while the nature of surfactant, S, had the lowest. The ranking for the individual effects of the variables on F and k1 was C > N > S, on t80 and k2 was C > N approximately = S, was on t1 was C = N = S. The interactions between S and C were largest for F, t80 and k2, and lowest for k1 and t1. The ranking of the interaction effects of the variables on F and k2 was S-C > N-C > N-S, on t80 was S-C > N-S approximately = N-C, on k1 was N-C > N-S > S-C, and on t1 was N-S = N-C > S-C. The results suggest that the individual and interaction effects of formulation variables would provide useful guides in optimizing metronidazole suppository formulations.

Durability reliability analysis for corroding concrete structures under uncertainty

NASA Astrophysics Data System (ADS)

Zhang, Hao

2018-02-01

This paper presents a durability reliability analysis of reinforced concrete structures subject to the action of marine chloride. The focus is to provide insight into the role of epistemic uncertainties on durability reliability. The corrosion model involves a number of variables whose probabilistic characteristics cannot be fully determined due to the limited availability of supporting data. All sources of uncertainty, both aleatory and epistemic, should be included in the reliability analysis. Two methods are available to formulate the epistemic uncertainty: the imprecise probability-based method and the purely probabilistic method in which the epistemic uncertainties are modeled as random variables. The paper illustrates how the epistemic uncertainties are modeled and propagated in the two methods, and shows how epistemic uncertainties govern the durability reliability.

Stage-by-Stage and Parallel Flow Path Compressor Modeling for a Variable Cycle Engine

NASA Technical Reports Server (NTRS)

Kopasakis, George; Connolly, Joseph W.; Cheng, Larry

2015-01-01

This paper covers the development of stage-by-stage and parallel flow path compressor modeling approaches for a Variable Cycle Engine. The stage-by-stage compressor modeling approach is an extension of a technique for lumped volume dynamics and performance characteristic modeling. It was developed to improve the accuracy of axial compressor dynamics over lumped volume dynamics modeling. The stage-by-stage compressor model presented here is formulated into a parallel flow path model that includes both axial and rotational dynamics. This is done to enable the study of compressor and propulsion system dynamic performance under flow distortion conditions. The approaches utilized here are generic and should be applicable for the modeling of any axial flow compressor design.

Alternative bi-Hamiltonian structures for WDVV equations of associativity

NASA Astrophysics Data System (ADS)

Kalayci, J.; Nutku, Y.

1998-01-01

The WDVV equations of associativity in two-dimensional topological field theory are completely integrable third-order Monge-Ampère equations which admit bi-Hamiltonian structure. The time variable plays a distinguished role in the discussion of Hamiltonian structure, whereas in the theory of WDVV equations none of the independent variables merits such a distinction. WDVV equations admit very different alternative Hamiltonian structures under different possible choices of the time variable, but all these various Hamiltonian formulations can be brought together in the framework of the covariant theory of symplectic structure. They can be identified as different components of the covariant Witten-Zuckerman symplectic 2-form current density where a variational formulation of the WDVV equation that leads to the Hamiltonian operator through the Dirac bracket is available.

In-vitro release and permeation studies of ketoconazole from optimized dermatological vehicles using powder, nanoparticles and solid dispersion forms of drug

NASA Astrophysics Data System (ADS)

Mohammed, Irfan A.

To optimize the clinical efficacy of Ketoconazole from an externally applied product, this project was undertaken to evaluate the drug release/permeation profile from various dermatological vehicles using regular powder, nanoparticles and solid dispersion forms with reduced level of drug. Nanoparticles of drug were prepared by wet media milling method using Polyvinylpyrrolidone (PVP-10K) as a stabilizer. The nanoparticles were in the size range of 250-300nm. Solid dispersion was prepared by solvent evaporation method using drug to PVP-10K at a weight ratio of (1:2). Formulations containing 1% w/w drug were developed using HPMC gel, Carbomer gel and a cationic cream as the vehicles. Penetration enhancers including propylene glycol (PG), dimethylsulfoxide (DMSO) and polyethylene glycol 400 (PEG-400) at various levels were evaluated. A commercial 2% w/w ketoconazole product was included as a control for comparison. Studies were carried out with Franz Diffusion Cells using cellulose membrane and human cadaver skin for two and six hour studies. Among the formulations evaluated, the general rank order of the drug release through the cellulose membrane was observed to be: HPMC gel base > Anionic gel base > Cationic gel base > Commercial product. The addition of penetration enhancers showed variable effects in all samples evaluated. However, the HPMC gel-based vehicle showed significant effect in enhancing the drug release in the presence of DMSO. The formulation containing 1% w/w ketoconazole and 20% w/w DMSO gave a maximum drug release of 20.21% when compared to only 1.60% from the commercial product. This represents a twelve fold increase in the release of ketoconazole from the formulation. Furthermore, when the optimum gel-based formulation containing 1% w/w ketoconazole was studied over an extended period of 6 hours, it gave 36.01% drug release from the sample formulation compared to only 2.00% from the commercial product. Finally, this formulation was selected to study for its drug release/permeation profile using the human cadaver skin as the diffusion barrier. Here, as expected, the drug release from both the formulations tested was significantly reduced due to the resistance posed by the skin. After 6 hours, the drug release form the commercial product was 0.17% when compared to 2.80% from the optimum formulation. Once again, this indicated that the experimental formulation exhibits superior drug release dynamics. The selected formulations were further evaluated for their in-vitro anti-fungal activities using yeast microorganisms. The results correlated to the in-vitro drug release profile, where HPMC based formulations exhibited a greater area of zone of inhibition for the growth of microorganisms when compared to diminutive area of zone of inhibition for the commercial product. The release data from all the samples were treated to calculate various physical parameters including: diffusion co-efficient, partition co-efficient, steady state flux and lag period etc. Interestingly, the values for the steady state flux and diffusion coefficient were found to be the highest from the optimum formulation and the values for the lag time and partition coefficient were observed to be the lowest. This supports the evidence that the drug from this formulation is readily diffusible to the skin at a steady rate after its application at the site. In-vitro drug diffusion studies and in-vitro anti-fungal studies proved useful in screening various dermatological formulations of ketoconazole compared to the commercial product containing 2% w/w drug. The HPMC based optimum formulation with reduced level of drug represents 15 folds increase through human cadaver skin and also exhibited augmented anti-fungal activity. This supports that by using an appropriate vehicle and proper incorporation of drug, one can optimize the drug release from topical formulation for maximum therapeutic effect.

Screening of formulation variables for the preparation of poly(epsilon-caprolactone) nanocapsules containing the local anesthetic benzocaine.

PubMed

Moraes, Carolina Morales; de Matos, Angélica Prado; Grillo, Renato; de Melo, Nathalie F S; de Paula, Eneida; Dias Filho, Newton Luiz; Rosa, André Henrique; Fraceto, Leonardo Fernandes

2011-03-01

In this work we describe the screening of four parameters in the preparation, by nanoprecipitation, of poly(epsilon-caprolactone) nanocapsules, used as a drug carrier system for the local anesthetic, benzocaine. A 2(4-1) factorial experimental design was used to study the influence of four different independent variables (polymer, oily phase, Span 60 and Tween 80) on nanocapsule characteristics (size, polydispersion index, zeta potential) and drug loading capability. Best results were obtained using an aqueous formulation comprising 100 mg of polymer, 200 mg of oily phase, 40 mg of Span 60 and 60 mg of Tween 80 in a final volume of 10 mL which produced a colloidal system with particle size of 188 nm, zeta potential -32 mV, polydispersion index 0.07, and benzocaine association efficiency > 87%. These findings open the way for future clinical studies using such formulations.

Advances of the smooth variable structure filter: square-root and two-pass formulations

NASA Astrophysics Data System (ADS)

Gadsden, S. Andrew; Lee, Andrew S.

2017-01-01

The smooth variable structure filter (SVSF) has seen significant development and research activity in recent years. It is based on sliding mode concepts, which utilize a switching gain that brings an inherent amount of stability to the estimation process. In an effort to improve upon the numerical stability of the SVSF, a square-root formulation is derived. The square-root SVSF is based on Potter's algorithm. The proposed formulation is computationally more efficient and reduces the risks of failure due to numerical instability. The new strategy is applied on target tracking scenarios for the purposes of state estimation, and the results are compared with the popular Kalman filter. In addition, the SVSF is reformulated to present a two-pass smoother based on the SVSF gain. The proposed method is applied on an aerospace flight surface actuator, and the results are compared with the Kalman-based two-pass smoother.

Nanoethosomes mediated transdermal delivery of vinpocetine for management of Alzheimer's disease.

PubMed

Moghaddam, Atefeh Afshar; Aqil, Mohd; Ahmad, Farhan J; Ali, Mushir M; Sultana, Yasmin; Ali, Asgar

2015-12-01

To develop and statistically optimize nanoethosomal formulation for transdermal delivery of vinpocetine as an anti-Alzheimer's drug. Box-Behnken experimental design was applied for optimization of nanoethosomes. The independent variables were phospholipid (X 1 ), Tween 80 (X 2 ) and Ethanol (X 3 ) while entrapment efficiency (Y 1 ), particle sizes (Y 2 ), elasticity (Y 3 ) and flux (Y 4 ) were the dependent variables. Optimized nanoethosomal vinpocetine formulation with mean particle size 50.57 ± 26.11 nm showed 97.51 ± 0.86% entrapment efficiency, achieved mean transdermal flux 925.60 ± 39.80 µg/cm 2 /h and elasticity of 86.61 ± 2.88. Ex-vivo study of nanoethosomal formulation showed a significant increase flux and entrapment efficiency compared with control vinpocetine solution. Our results suggest that nanoethosome is an efficient carrier for transdermal delivery of vinpocetine as compared to its oral form.

Stacking-sequence optimization for buckling of laminated plates by integer programming

NASA Technical Reports Server (NTRS)

Haftka, Raphael T.; Walsh, Joanne L.

1991-01-01

Integer-programming formulations for the design of symmetric and balanced laminated plates under biaxial compression are presented. Both maximization of buckling load for a given total thickness and the minimization of total thickness subject to a buckling constraint are formulated. The design variables that define the stacking sequence of the laminate are zero-one integers. It is shown that the formulation results in a linear optimization problem that can be solved on readily available software. This is in contrast to the continuous case, where the design variables are the thicknesses of layers with specified ply orientations, and the optimization problem is nonlinear. Constraints on the stacking sequence such as a limit on the number of contiguous plies of the same orientation and limits on in-plane stiffnesses are easily accommodated. Examples are presented for graphite-epoxy plates under uniaxial and biaxial compression using a commercial software package based on the branch-and-bound algorithm.

Development of nanostructured lipid carriers containing salicyclic acid for dermal use based on the Quality by Design method.

PubMed

Kovács, A; Berkó, Sz; Csányi, E; Csóka, I

2017-03-01

The aim of our present work was to evaluate the applicability of the Quality by Design (QbD) methodology in the development and optimalization of nanostructured lipid carriers containing salicyclic acid (NLC SA). Within the Quality by Design methology, special emphasis is layed on the adaptation of the initial risk assessment step in order to properly identify the critical material attributes and critical process parameters in formulation development. NLC SA products were formulated by the ultrasonication method using Compritol 888 ATO as solid lipid, Miglyol 812 as liquid lipid and Cremophor RH 60® as surfactant. LeanQbD Software and StatSoft. Inc. Statistica for Windows 11 were employed to indentify the risks. Three highly critical quality attributes (CQAs) for NLC SA were identified, namely particle size, particle size distribution and aggregation. Five attributes of medium influence were identified, including dissolution rate, dissolution efficiency, pH, lipid solubility of the active pharmaceutical ingredient (API) and entrapment efficiency. Three critical material attributes (CMA) and critical process parameters (CPP) were identified: surfactant concentration, solid lipid/liquid lipid ratio and ultrasonication time. The CMAs and CPPs are considered as independent variables and the CQAs are defined as dependent variables. The 2 3 factorial design was used to evaluate the role of the independent and dependent variables. Based on our experiments, an optimal formulation can be obtained when the surfactant concentration is set to 5%, the solid lipid/liquid lipid ratio is 7:3 and ultrasonication time is 20min. The optimal NLC SA showed narrow size distribution (0.857±0.014) with a mean particle size of 114±2.64nm. The NLC SA product showed a significantly higher in vitro drug release compared to the micro-particle reference preparation containing salicylic acid (MP SA). Copyright © 2016 Elsevier B.V. All rights reserved.

Conceptuation, formulation and evaluation of sustained release floating tablets of captopril compression coated with gastric dispersible hydrochlorothiazide using 23 factorial design

PubMed Central

Sirisha, Pathuri Lakshmi; Babu, Govada Kishore; Babu, Puttagunta Srinivasa

2014-01-01

Ambulatory blood pressure monitoring is regarded as the gold standard for hypertensive therapy in non-dipping hypertension patients. A novel compression coated formulation of captopril and hydrochlorothiazide (HCTZ) was developed in order to improve the efficacy of antihypertensive therapy considering the half-life of both drugs. The synergistic action using combination therapy can be effectively achieved by sustained release captopril (t1/2= 2.5 h) and fast releasing HCTZ (average t1/2= 9.5 h). The sustained release floating tablets of captopril were prepared by using 23 factorial design by employing three polymers i.e., ethyl cellulose (EC), carbopol and xanthan gum at two levels. The formulations (CF1-CF8) were optimized using analysis of variance for two response variables, buoyancy and T50%. Among the three polymers employed, the coefficients and P values for the response variable buoyancy and T50% using EC were found to be 3.824, 0.028 and 0.0196, 0.046 respectively. From the coefficients and P values for the two response variables, formulation CF2 was optimized, which contains EC polymer alone at a high level. The CF2 formulation was further compression coated with optimized gastric dispersible HCTZ layer (HF9). The compression coated tablet was further evaluated using drug release kinetics. The Q value of HCTZ layer is achieved within 20 min following first order release whereas the Q value of captopril was obtained at 6.5 h following Higuchi model, from which it is proved that rapid release HCTZ and slow release of captopril is achieved. The mechanism of drug release was analyzed using Peppas equation, which showed an n >0.90 confirming case II transportation mechanism for drug release. PMID:25006552

Stability of buffer-free freeze-dried formulations: A feasibility study of a monoclonal antibody at high protein concentrations.

PubMed

Garidel, Patrick; Pevestorf, Benjamin; Bahrenburg, Sven

2015-11-01

We studied the stability of freeze-dried therapeutic protein formulations over a range of initial concentrations (from 40 to 160 mg/mL) and employed a variety of formulation strategies (including buffer-free freeze dried formulations, or BF-FDF). Highly concentrated, buffer-free liquid formulations of therapeutic monoclonal antibodies (mAbs) have been shown to be a viable alternative to conventionally buffered preparations. We considered whether it is feasible to use the buffer-free strategy in freeze-dried formulations, as an answer to some of the known drawbacks of conventional buffers. We therefore conducted an accelerated stability study (24 weeks at 40 °C) to assess the feasibility of stabilizing freeze-dried formulations without "classical" buffer components. Factors monitored included pH stability, protein integrity, and protein aggregation. Because the protein solutions are inherently self-buffering, and the system's buffer capacity scales with protein concentration, we included highly concentrated buffer-free freeze-dried formulations in the study. The tested formulations ranged from "fully formulated" (containing both conventional buffer and disaccharide stabilizers) to "buffer-free" (including formulations with only disaccharide lyoprotectant stabilizers) to "excipient-free" (with neither added buffers nor stabilizers). We evaluated the impacts of varying concentrations, buffering schemes, pHs, and lyoprotectant additives. At the end of 24 weeks, no change in pH was observed in any of the buffer-free formulations. Unbuffered formulations were found to have shorter reconstitution times and lower opalescence than buffered formulations. Protein stability was assessed by visual inspection, sub-visible particle analysis, protein monomer content, charge variants analysis, and hydrophobic interaction chromatography. All of these measures found the stability of buffer-free formulations that included a disaccharide stabilizer comparable to buffer-based formulations, especially at protein concentrations up to and including 115 mg/mL. Copyright © 2015 Elsevier B.V. All rights reserved.

Optimizing Placement of Weather Stations: Exploring Objective Functions of Meaningful Combinations of Multiple Weather Variables

NASA Astrophysics Data System (ADS)

Snyder, A.; Dietterich, T.; Selker, J. S.

2017-12-01

Many regions of the world lack ground-based weather data due to inadequate or unreliable weather station networks. For example, most countries in Sub-Saharan Africa have unreliable, sparse networks of weather stations. The absence of these data can have consequences on weather forecasting, prediction of severe weather events, agricultural planning, and climate change monitoring. The Trans-African Hydro-Meteorological Observatory (TAHMO.org) project seeks to address these problems by deploying and operating a large network of weather stations throughout Sub-Saharan Africa. To design the TAHMO network, we must determine where to place weather stations within each country. We should consider how we can create accurate spatio-temporal maps of weather data and how to balance the desired accuracy of each weather variable of interest (precipitation, temperature, relative humidity, etc.). We can express this problem as a joint optimization of multiple weather variables, given a fixed number of weather stations. We use reanalysis data as the best representation of the "true" weather patterns that occur in the region of interest. For each possible combination of sites, we interpolate the reanalysis data between selected locations and calculate the mean average error between the reanalysis ("true") data and the interpolated data. In order to formulate our multi-variate optimization problem, we explore different methods of weighting each weather variable in our objective function. These methods include systematic variation of weights to determine which weather variables have the strongest influence on the network design, as well as combinations targeted for specific purposes. For example, we can use computed evapotranspiration as a metric that combines many weather variables in a way that is meaningful for agricultural and hydrological applications. We compare the errors of the weather station networks produced by each optimization problem formulation. We also compare these errors to those of manually designed weather station networks in West Africa, planned by the respective host-country's meteorological agency.

High-order polygonal discontinuous Petrov-Galerkin (PolyDPG) methods using ultraweak formulations

NASA Astrophysics Data System (ADS)

Vaziri Astaneh, Ali; Fuentes, Federico; Mora, Jaime; Demkowicz, Leszek

2018-04-01

This work represents the first endeavor in using ultraweak formulations to implement high-order polygonal finite element methods via the discontinuous Petrov-Galerkin (DPG) methodology. Ultraweak variational formulations are nonstandard in that all the weight of the derivatives lies in the test space, while most of the trial space can be chosen as copies of $L^2$-discretizations that have no need to be continuous across adjacent elements. Additionally, the test spaces are broken along the mesh interfaces. This allows one to construct conforming polygonal finite element methods, termed here as PolyDPG methods, by defining most spaces by restriction of a bounding triangle or box to the polygonal element. The only variables that require nontrivial compatibility across elements are the so-called interface or skeleton variables, which can be defined directly on the element boundaries. Unlike other high-order polygonal methods, PolyDPG methods do not require ad hoc stabilization terms thanks to the crafted stability of the DPG methodology. A proof of convergence of the form $h^p$ is provided and corroborated through several illustrative numerical examples. These include polygonal meshes with $n$-sided convex elements and with highly distorted concave elements, as well as the modeling of discontinuous material properties along an arbitrary interface that cuts a uniform grid. Since PolyDPG methods have a natural a posteriori error estimator a polygonal adaptive strategy is developed and compared to standard adaptivity schemes based on constrained hanging nodes. This work is also accompanied by an open-source $\\texttt{PolyDPG}$ software supporting polygonal and conventional elements.

Loteprednol Etabonate Nanoparticles: Optimization via Box-Behnken Design Response Surface Methodology and Physicochemical Characterization.

PubMed

Sah, Abhishek K; Suresh, Preeti K

2017-01-01

Abstract: The objective of the present work was to prepare and optimize the loteprednoletabonate (LE) loaded poly (D,L-lactide co-glycolide) (PLGA) polymer based nanoparticle carrier. The review on recent patents (US9006241, US20130224302A1, US2012/0028947A1) assisted in the selection of drug and polymer for designing nanoparticles for ocular delivery applications. The nanoparticles were prepared by solvent evaporation followed by high speed homogenization. Biodegradable polymer PLGA (50:50) grade was utilized to develop various formulations with different drug:polymer ratio. A Box-Behnken design with 33 factorial design was selected for the present study and 17 runs were carried out in totality. The influence of various process variables (viz., polymer concentration, homogenization speed and sonication time) on the characteristics of nanoparticles including the in vitro drug release profile were studied. The nanoparticulate formulations were evaluated for mean spherical diameter, polydispersity index (PDI), zeta potential, surface morphology, drug entrapment and in-vitro drug release profile. The entrapment efficiency, drug loading and mean particle size were found to be 96.31±1.68 %, 35.46±0.35 % and 167.6±2.1 nm respectively. The investigated process and formulation variables were found to have significant effect on the particle size, drug loading (DL), entrapment efficiency (EE), and in vitro drug release profile. A biphasic in vitro drug release profile was apparent from the optimized nanoparticles (NPs) for 24 hours. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A LES-CMC formulation for premixed flames including differential diffusion

NASA Astrophysics Data System (ADS)

Farrace, Daniele; Chung, Kyoungseoun; Bolla, Michele; Wright, Yuri M.; Boulouchos, Konstantinos; Mastorakos, Epaminondas

2018-05-01

A finite volume large eddy simulation-conditional moment closure (LES-CMC) numerical framework for premixed combustion developed in a previous studyhas been extended to account for differential diffusion. The non-unity Lewis number CMC transport equation has an additional convective term in sample space proportional to the conditional diffusion of the progress variable, that in turn accounts for diffusion normal to the flame front and curvature-induced effects. Planar laminar simulations are first performed using a spatially homogeneous non-unity Lewis number CMC formulation and validated against physical-space fully resolved reference solutions. The same CMC formulation is subsequently used to numerically investigate the effects of curvature for laminar flames having different effective Lewis numbers: a lean methane-air flame with Leeff = 0.99 and a lean hydrogen-air flame with Leeff = 0.33. Results suggest that curvature does not affect the conditional heat release if the effective Lewis number tends to unity, so that curvature-induced transport may be neglected. Finally, the effect of turbulence on the flame structure is qualitatively analysed using LES-CMC simulations with and without differential diffusion for a turbulent premixed bluff body methane-air flame exhibiting local extinction behaviour. Overall, both the unity and the non-unity computations predict the characteristic M-shaped flame observed experimentally, although some minor differences are identified. The findings suggest that for the high Karlovitz number (from 1 to 10) flame considered, turbulent mixing within the flame weakens the differential transport contribution by reducing the conditional scalar dissipation rate and accordingly the conditional diffusion of the progress variable.

Application of a central composite design to evaluate the influence of colouring agents in lipstick formulation.

PubMed

Zibetti, F M; Cardoso, A C A; Desmarais, G C; de Almeida, K B; do Nascimento, L M; Rolim, L F; Rocha, M S; Duarte, N G D; Azevedo, P H R A; Araújo, J L; Mourão, S C; Falcão, D Q

2016-10-01

The aim of this study was to evaluate by central composite design the influence of colouring agents in lipstick colour, expressed by L*, a*, b* parameters (CIELab system) where L* indicates lightness, and a* and b* are the chromaticity coordinates. The a* indicates colour direction from red to green and b* from yellow to blue. Lipsticks were formulated as described by (Recent Adv. Prosp. Potent Med. Plants, 2009 and 39). The combined effect of three variables (dye, pigment and opacifier) was evaluated by different formulations in a central composite design. Colour parameters (L*, a*, b*) were analysed by reflectance spectrophotometry. Lipsticks were characterized by visual analyses and melting point. All formulations were integrate and homogeneous. The pigments and dye do not influence in colour transfer neither in melting point of lipsticks. On the other hand, results indicated that variables studied show influence only in parameter b*, whereas for L* and a* values there was no significant difference (P < 0.05). It was possible to verify that only the colour parameter b* was influenced by the variation in colouring agent's concentrations in lipstick formulation, leading to the production of the colour ranging between violet and light red. Such results are useful for developing new lipstick formulations to obtain the desired colour in the final product. © 2016 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Low-cost, ready-to-use therapeutic foods can be designed using locally available commodities with the aid of linear programming.

PubMed

Dibari, Filippo; Diop, El Hadji I; Collins, Steven; Seal, Andrew

2012-05-01

According to the United Nations (UN), 25 million children <5 y of age are currently affected by severe acute malnutrition and need to be treated using special nutritional products such as ready-to-use therapeutic foods (RUTF). Improved formulations are in demand, but a standardized approach for RUTF design has not yet been described. A method relying on linear programming (LP) analysis was developed and piloted in the design of a RUTF prototype for the treatment of wasting in East African children and adults. The LP objective function and decision variables consisted of the lowest formulation price and the weights of the chosen commodities (soy, sorghum, maize, oil, and sugar), respectively. The LP constraints were based on current UN recommendations for the macronutrient content of therapeutic food and included palatability, texture, and maximum food ingredient weight criteria. Nonlinear constraints for nutrient ratios were converted to linear equations to allow their use in LP. The formulation was considered accurate if laboratory results confirmed an energy density difference <10% and a protein or lipid difference <5 g · 100 g(-1) compared to the LP formulation estimates. With this test prototype, the differences were 7%, and 2.3 and -1.0 g · 100 g(-1), respectively, and the formulation accuracy was considered good. LP can contribute to the design of ready-to-use foods (therapeutic, supplementary, or complementary), targeting different forms of malnutrition, while using commodities that are cheaper, regionally available, and meet local cultural preferences. However, as with all prototype feeding products for medical use, composition analysis, safety, acceptability, and clinical effectiveness trials must be conducted to validate the formulation.

New formulations of amoxicillin/clavulanic acid: a pharmacokinetic and pharmacodynamic review.

PubMed

Sánchez Navarro, Amparo

2005-01-01

The pharmacokinetic properties of amoxicillin and clavulanic acid when used alone or in combination are extensively reviewed and discussed in this article. The reported data support a nonlinear absorption process for amoxicillin. Saturable transport mechanisms, limited solubility and the existence of an absorption window are possibly involved in the gastrointestinal absorption of this antibacterial, all leading to a decrease in the peak plasma concentration (Cmax)/dose ratio, a prolongation of the time to reach Cmax, and broad variability for high doses of amoxicillin. Data available in the literature also suggest a possible interaction between amoxicillin and clavulanic acid that might decrease the absolute bioavailability of clavulanic acid. In the present review the intrinsic pharmacodynamics of each drug, together with the synergism produced by the amoxicillin/clavulanic acid association, are also reviewed and analysed. Not only beta-lactamase-producing strains, but also Streptococcus pneumoniae strains, seem to be more efficiently eradicated by the association of amoxicillin and clavulanic acid, and a relevant post-antibacterial effect and post-beta-lactamase inhibitor effect are likely to operate when amoxicillin is administered together with clavulanic acid. The principles of pharmacokinetic/pharmacodynamic analysis applied to amoxicillin are reviewed, with special emphasis being placed on the results obtained from in vitro studies and animal models regarding the new pharmacokinetically enhanced formulation. Theoretical considerations concerning the efficacy of this formulation provided by the application of pharmacokinetic/pharmacodynamic analysis to the scarce pharmacokinetic data available are also included. The broad pharmacokinetic variability of both amoxicillin and clavulanic acid, particularly when administered together and at high doses of amoxicillin, is highlighted and the interest in considering this aspect to improve predictions based on pharmacokinetic/pharmacodynamic analyses for the new formulations is indicated. Methodological recommendations such as the Monte Carlo simulation are proposed in order to obtain more realistic predictions in clinical practice.

State space approach to mixed boundary value problems.

NASA Technical Reports Server (NTRS)

Chen, C. F.; Chen, M. M.

1973-01-01

A state-space procedure for the formulation and solution of mixed boundary value problems is established. This procedure is a natural extension of the method used in initial value problems; however, certain special theorems and rules must be developed. The scope of the applications of the approach includes beam, arch, and axisymmetric shell problems in structural analysis, boundary layer problems in fluid mechanics, and eigenvalue problems for deformable bodies. Many classical methods in these fields developed by Holzer, Prohl, Myklestad, Thomson, Love-Meissner, and others can be either simplified or unified under new light shed by the state-variable approach. A beam problem is included as an illustration.

User's manual for Axisymmetric Diffuser Duct (ADD) code. Volume 1: General ADD code description

NASA Technical Reports Server (NTRS)

Anderson, O. L.; Hankins, G. B., Jr.; Edwards, D. E.

1982-01-01

This User's Manual contains a complete description of the computer codes known as the AXISYMMETRIC DIFFUSER DUCT code or ADD code. It includes a list of references which describe the formulation of the ADD code and comparisons of calculation with experimental flows. The input/output and general use of the code is described in the first volume. The second volume contains a detailed description of the code including the global structure of the code, list of FORTRAN variables, and descriptions of the subroutines. The third volume contains a detailed description of the CODUCT code which generates coordinate systems for arbitrary axisymmetric ducts.

The effects of finite rate chemical processes on high enthalpy nozzle performance - A comparison between SPARK and SEAGULL

NASA Technical Reports Server (NTRS)

Carpenter, M. H.

1988-01-01

The generalized chemistry version of the computer code SPARK is extended to include two higher-order numerical schemes, yielding fourth-order spatial accuracy for the inviscid terms. The new and old formulations are used to study the influences of finite rate chemical processes on nozzle performance. A determination is made of the computationally optimum reaction scheme for use in high-enthalpy nozzles. Finite rate calculations are compared with the frozen and equilibrium limits to assess the validity of each formulation. In addition, the finite rate SPARK results are compared with the constant ratio of specific heats (gamma) SEAGULL code, to determine its accuracy in variable gamma flow situations. Finally, the higher-order SPARK code is used to calculate nozzle flows having species stratification. Flame quenching occurs at low nozzle pressures, while for high pressures, significant burning continues in the nozzle.

Multi-phase-field modeling of anisotropic crack propagation for polycrystalline materials

NASA Astrophysics Data System (ADS)

Nguyen, Thanh-Tung; Réthoré, Julien; Yvonnet, Julien; Baietto, Marie-Christine

2017-08-01

A new multi-phase-field method is developed for modeling the fracture of polycrystals at the microstructural level. Inter and transgranular cracking, as well as anisotropic effects of both elasticity and preferential cleavage directions within each randomly oriented crystal are taken into account. For this purpose, the proposed phase field formulation includes: (a) a smeared description of grain boundaries as cohesive zones avoiding defining an additional phase for grains; (b) an anisotropic phase field model; (c) a multi-phase field formulation where each preferential cleavage direction is associated with a damage (phase field) variable. The obtained framework allows modeling interactions and competition between grains and grain boundary cracks, as well as their effects on the effective response of the material. The proposed model is illustrated through several numerical examples involving a full description of complex crack initiation and propagation within 2D and 3D models of polycrystals.

Solving the Inverse-Square Problem with Complex Variables

ERIC Educational Resources Information Center

Gauthier, N.

2005-01-01

The equation of motion for a mass that moves under the influence of a central, inverse-square force is formulated and solved as a problem in complex variables. To find the solution, the constancy of angular momentum is first established using complex variables. Next, the complex position coordinate and complex velocity of the particle are assumed…

Numerical Simulation of Bow Waves and Transom-Stern Flows

NASA Astrophysics Data System (ADS)

Dommermuth, Douglas G.; Schlageter, Eric A.; Talcott, John C.; Wyatt, Donald C.; Novikov, Evgeny A.

1997-11-01

A stratified-flow formulation is used to model the breaking bow wave and the separated transom-stern flow that are generated by a ship moving with forward speed. The interface of the air with the water is identified as the zero level-set of a three-dimensional function. The ship is modeled using a body-force technique on a cartesian grid. The three-dimensional body-force is generated using a surface panelization of the entire ship, including the above-water geometry up to and including the deck. The effects of surface tension are modeled as a source term that is concentrated at the air-water interface. The effects of gravity are modeled as a volumetric force. The three-dimensional, unsteady, Navier-Stokes equations are expressed in primitive-variable form. A LES formulation with a Smagorinsky sub-grid-scale model is used to model turbulence. Numerical convergence is demonstrated using 128x64x65, 256x128x129, and 512x256x257 grid points. The numerical results compare well to whisker-probe measurements of the free-surface elevation generated by a naval combatant.

Hierarchic Extensions in the Static and Dynamic Analysis of Elastic Beams. Ph.D. Thesis, 1990 Final Report, May 1990

NASA Technical Reports Server (NTRS)

Watson, Robert A.

1991-01-01

Approximate solutions of static and dynamic beam problems by the p-version of the finite element method are investigated. Within a hierarchy of engineering beam idealizations, rigorous formulations of the strain and kinetic energies for straight and circular beam elements are presented. These formulations include rotating coordinate system effects and geometric nonlinearities to allow for the evaluation of vertical axis wind turbines, the motivating problem for this research. Hierarchic finite element spaces, based on extensions of the polynomial orders used to approximate the displacement variables, are constructed. The developed models are implemented into a general purpose computer program for evaluation. Quality control procedures are examined for a diverse set of sample problems. These procedures include estimating discretization errors in energy norm and natural frequencies, performing static and dynamic equilibrium checks, observing convergence for qualities of interest, and comparison with more exacting theories and experimental data. It is demonstrated that p-extensions produce exponential rates of convergence in the approximation of strain energy and natural frequencies for the class of problems investigated.

Formulation and method for preparing gels comprising hydrous aluminum oxide

DOEpatents

Collins, Jack L.

2014-06-17

Formulations useful for preparing hydrous aluminum oxide gels contain a metal salt including aluminum, an organic base, and a complexing agent. Methods for preparing gels containing hydrous aluminum oxide include heating a formulation to a temperature sufficient to induce gel formation, where the formulation contains a metal salt including aluminum, an organic base, and a complexing agent.

Formulation and method for preparing gels comprising hydrous cerium oxide

DOEpatents

Collins, Jack L; Chi, Anthony

2013-05-07

Formulations useful for preparing hydrous cerium oxide gels contain a metal salt including cerium, an organic base, and a complexing agent. Methods for preparing gels containing hydrous cerium oxide include heating a formulation to a temperature sufficient to induce gel formation, where the formulation contains a metal salt including cerium, an organic base, and a complexing agent.

Bv and Bfv Formulation of a Gauge Theory of Quadratic Lie Algebras in 2d and a Construction of W3 Topological Gravity

NASA Astrophysics Data System (ADS)

Dayi, Ömer F.

The recently proposed generalized field method for solving the master equation of Batalin and Vilkovisky is applied to a gauge theory of quadratic Lie algebras in two dimensions. The charge corresponding to BRST symmetry derived from this solution in terms of the phase space variables by using the Noether procedure, and the one found due to the BFV-method are compared and found to coincide. W3-algebra, formulated in terms of a continuous variable is exploit in the mentioned gauge theory to construct a W3 topological gravity. Moreover, its gauge fixing is briefly discussed.

Global, Multi-Objective Trajectory Optimization With Parametric Spreading

NASA Technical Reports Server (NTRS)

Vavrina, Matthew A.; Englander, Jacob A.; Phillips, Sean M.; Hughes, Kyle M.

2017-01-01

Mission design problems are often characterized by multiple, competing trajectory optimization objectives. Recent multi-objective trajectory optimization formulations enable generation of globally-optimal, Pareto solutions via a multi-objective genetic algorithm. A byproduct of these formulations is that clustering in design space can occur in evolving the population towards the Pareto front. This clustering can be a drawback, however, if parametric evaluations of design variables are desired. This effort addresses clustering by incorporating operators that encourage a uniform spread over specified design variables while maintaining Pareto front representation. The algorithm is demonstrated on a Neptune orbiter mission, and enhanced multidimensional visualization strategies are presented.

Subgrid-scale Condensation Modeling for Entropy-based Large Eddy Simulations of Clouds

NASA Astrophysics Data System (ADS)

Kaul, C. M.; Schneider, T.; Pressel, K. G.; Tan, Z.

2015-12-01

An entropy- and total water-based formulation of LES thermodynamics, such as that used by the recently developed code PyCLES, is advantageous from physical and numerical perspectives. However, existing closures for subgrid-scale thermodynamic fluctuations assume more traditional choices for prognostic thermodynamic variables, such as liquid potential temperature, and are not directly applicable to entropy-based modeling. Since entropy and total water are generally nonlinearly related to diagnosed quantities like temperature and condensate amounts, neglecting their small-scale variability can lead to bias in simulation results. Here we present the development of a subgrid-scale condensation model suitable for use with entropy-based thermodynamic formulations.

Optimization of Robust HPLC Method for Quantitation of Ambroxol Hydrochloride and Roxithromycin Using a DoE Approach.

PubMed

Patel, Rashmin B; Patel, Nilay M; Patel, Mrunali R; Solanki, Ajay B

2017-03-01

The aim of this work was to develop and optimize a robust HPLC method for the separation and quantitation of ambroxol hydrochloride and roxithromycin utilizing Design of Experiment (DoE) approach. The Plackett-Burman design was used to assess the impact of independent variables (concentration of organic phase, mobile phase pH, flow rate and column temperature) on peak resolution, USP tailing and number of plates. A central composite design was utilized to evaluate the main, interaction, and quadratic effects of independent variables on the selected dependent variables. The optimized HPLC method was validated based on ICH Q2R1 guideline and was used to separate and quantify ambroxol hydrochloride and roxithromycin in tablet formulations. The findings showed that DoE approach could be effectively applied to optimize a robust HPLC method for quantification of ambroxol hydrochloride and roxithromycin in tablet formulations. Statistical comparison between results of proposed and reported HPLC method revealed no significant difference; indicating the ability of proposed HPLC method for analysis of ambroxol hydrochloride and roxithromycin in pharmaceutical formulations. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Combined mixture-process variable approach: a suitable statistical tool for nanovesicular systems optimization.

PubMed

Habib, Basant A; AbouGhaly, Mohamed H H

2016-06-01

This study aims to illustrate the applicability of combined mixture-process variable (MPV) design and modeling for optimization of nanovesicular systems. The D-optimal experimental plan studied the influence of three mixture components (MCs) and two process variables (PVs) on lercanidipine transfersomes. The MCs were phosphatidylcholine (A), sodium glycocholate (B) and lercanidipine hydrochloride (C), while the PVs were glycerol amount in the hydration mixture (D) and sonication time (E). The studied responses were Y1: particle size, Y2: zeta potential and Y3: entrapment efficiency percent (EE%). Polynomial equations were used to study the influence of MCs and PVs on each response. Response surface methodology and multiple response optimization were applied to optimize the formulation with the goals of minimizing Y1 and maximizing Y2 and Y3. The obtained polynomial models had prediction R(2) values of 0.645, 0.947 and 0.795 for Y1, Y2 and Y3, respectively. Contour, Piepel's response trace, perturbation, and interaction plots were drawn for responses representation. The optimized formulation, A: 265 mg, B: 10 mg, C: 40 mg, D: zero g and E: 120 s, had desirability of 0.9526. The actual response values for the optimized formulation were within the two-sided 95% prediction intervals and were close to the predicted values with maximum percent deviation of 6.2%. This indicates the validity of combined MPV design and modeling for optimization of transfersomal formulations as an example of nanovesicular systems.

Formulation and characterization of sustained release dosage form of moisture sensitive drug

PubMed Central

Patel, Priya; Dave, Abhishek; Vasava, Amit; Patel, Paresh

2015-01-01

Objective: The purpose of this study was to prepare sustained release tablet of moisture sensitive drug like Ranitidine Hydrochloride for treatment of gastroesophageal reflux disease along with the improvement of moisture stability to get better therapeutic efficacy. Materials and Methods: Pan coating technique was used for coating of the tablet. Film coating was done using Eudragit RLPO and Eugragit EPO as coating polymer. 32 full factorial design was applied for optimization purpose, and 9 runs were conducted. In that Eudragit RLPO and Eudragit EPO taken as an independent variables and moisture gain and Cummulative Drug Release (CDR) were taken as dependent variables. Drug and excipient compatibility was done using differential scanning calorimetry and Fourier transform infrared spectroscopy study. The tablet was evaluated for precompression parameter and all postcompression parameter. Stability study was carried out at room temperature (30°C ± 2°C/65% ± 5% relative humidity). Final formulation was compared with marketed formulation RANTEC 300. Result: Tablets were passing out all precompression parameter along with postcompression parameter. Stability study shows that the parameter such as hardness, friability, and dissolution are in the range. Hence, there is no significant change shown after stability study. Our final formulation was compared with marketed formulation RANTEC 300 and result demonstrates that our final formulation have less moisture gain and give release up to 12 h. Conclusion: The result of present study demonstrates that final formulation has less moisture gain and getting desired CDR for sustained release of drug. On the basis of all study, it was concluded that the tablet was coated by combination of Eudragit RLPO 10% and Eudragit EPO 10% give better result. This formation provided promising approach for the drug release up to 12 h for moisture sensitive drug like ranitidine hydrochloride. PMID:25838994

The Use of D-Optimal Mixture Design in Optimising Okara Soap Formulation for Stratum Corneum Application

PubMed Central

Borhan, Farrah Payyadhah; Abd Gani, Siti Salwa; Shamsuddin, Rosnah

2014-01-01

Okara, soybean waste from tofu and soymilk production, was utilised as a natural antioxidant in soap formulation for stratum corneum application. D-optimal mixture design was employed to investigate the influence of the main compositions of okara soap containing different fatty acid and oils (virgin coconut oil A (24–28% w/w), olive oil B (15–20% w/w), palm oil C (6–10% w/w), castor oil D (15–20% w/w), cocoa butter E (6–10% w/w), and okara F (2–7% w/w)) by saponification process on the response hardness of the soap. The experimental data were utilized to carry out analysis of variance (ANOVA) and to develop a polynomial regression model for okara soap hardness in terms of the six design factors considered in this study. Results revealed that the best mixture was the formulation that included 26.537% A, 19.999% B, 9.998% C, 16.241% D, 7.633% E, and 7.000% F. The results proved that the difference in the level of fatty acid and oils in the formulation significantly affects the hardness of soap. Depending on the desirable level of those six variables, creation of okara based soap with desirable properties better than those of commercial ones is possible. PMID:25548777

Characterization of the Physical Stability of a Lyophilized IgG1 mAb After Accelerated Shipping-like Stress

PubMed Central

Telikepalli, Srivalli; Kumru, Ozan S.; Kim, Jae Hyun; Joshi, Sangeeta B.; O'Berry, Kristin B.; Blake-Haskins, Angela W.; Perkins, Melissa D.; Middaugh, C. Russell; Volkin, David B.

2014-01-01

Upon exposure to shaking stress, an IgG1 mAb formulation in both liquid and lyophilized state formed subvisible particles. Since freeze-drying is expected to minimize protein physical instability under these conditions, the extent and nature of aggregate formation in the lyophilized preparation was examined using a variety of particle characterization techniques. The effect of formulation variables such as residual moisture content, reconstitution rate, and reconstitution medium were examined. Upon reconstitution of shake-stressed lyophilized mAb, differences in protein particle size and number were observed by Microflow Digital Imaging (MFI), with the reconstitution medium having the largest impact. Shake-stress had minor effects on the structure of protein within the particles as shown by SDS-PAGE and FTIR analysis. The lyophilized mAb was shake-stressed to different extents and stored for 3 months at different temperatures. Both extent of cake collapse and storage temperature affected the physical stability of the shake-stressed lyophilized mAb upon subsequent storage. These findings demonstrate that physical degradation upon shaking of a lyophilized IgG1 mAb formulation includes not only cake breakage, but also results in an increase in subvisible particles and turbidity upon reconstitution. The shaking-induced cake breakage of the lyophilized IgG1 mAb formulation also resulted in decreased physical stability upon storage. PMID:25522000

Combinatorial and high-throughput screening of the effect of siloxane composition on the surface properties of crosslinked siloxane-polyurethane coatings.

PubMed

Ekin, Abdullah; Webster, Dean C

2007-01-01

Libraries of siloxane-polyurethane coatings were designed, formulated, and screened using high-throughput experimentation. Four independent variables that were analyzed were the molecular weight of poly(dimethylsiloxane) (PDMS), presence or absence of poly(epsilon-caprolactone) (PCL) blocks attached to the PDMS backbone, the length of the PCL blocks, and the siloxane polymer level in the coating formulations. In addition to the siloxane libraries (3-aminopropyl-terminated PDMS and poly(epsilon-caprolactone)-poly(dimethylsiloxane)-poly(epsilon-caprolactone) (PCL-PDMS-PCL) triblock copolymers), the coating formulation included a trifunctional isocyanate crosslinker, trifunctional poly(epsilon-caprolactone) polyol, 2,4-pentanedione (pot-life extender), dibutyltin diacetate (catalyst), and a blend of solvents. The resulting coatings were analyzed for their surface energy and pseudobarnacle adhesion both before and after aging the coatings for 30 days in water. The water and methylene iodide contact angle averages increase with increasing molecular weight of PDMS. Coatings prepared from PCL-PDMS-PCL triblock copolymers have lower surface energies than coatings prepared from 3-aminopropyl-terminated PDMS; however, lower pseudobarnacle adhesion results were obtained for the coatings prepared from 3-aminopropyl-terminated PDMS than coatings prepared from PCL-PDMS-PCL triblock copolymers. The siloxane polymer level in the coating formulations does not have a significant effect on the surface energy of the coatings, but it resulted in higher pseudobarnacle adhesion.

Rapidly absorbed orodispersible tablet containing molecularly dispersed felodipine for management of hypertensive crisis: development, optimization and in vitro/in vivo studies.

PubMed

Basalious, Emad B; El-Sebaie, Wessam; El-Gazayerly, Omaima

2013-01-01

A liquisolid orodispersible tablet of felodipine, a BCS Class II drug, was developed to improve drug dissolution and absorption through the buccal mucosa for management of hypertensive crisis. A 24 full-factorial design was applied to optimize felodipine liquisolid systems (FLSs) having acceptable flow properties and possessing enhanced drug dissolution rates. Four formulation variables; The liquid type, X1 (PG or PEG), drug concentration, X2 (10% and 20%), type of coat, X3 (Aerosil® and Aeroperl®) and excipients ratio, X4 (10 and 20) were included in the design. The systems were assessed for dissolution and flow properties. Following optimization, the formulation components (X1, X2, X3 and X4) were PEG, 10%, Aerosil® and 20, respectively. The optimized FLS was compressed into felodipine liquisolid orodispersible tablet using Prosolv® as carrier material (FLODT-2). The in vitro and in vivo disintegration times of FLODT-2 were 9 and 7 s, respectively. The in vivo pharmacokinetic study using human volunteers showed a significant increase in dissolution and absorption rates of the formulation of FLODT-2 compared to soft gelatin capsules filled with felodipine solution in PEG under the same conditions. Our results proposed that the optimized FLODT formulation could be promising to manage hypertensive crisis.

Identification of variables influencing pharmaceutical interventions to improve medication review efficiency.

PubMed

Cornuault, Lauriane; Mouchel, Victorine; Phan Thi, Thuy-Tan; Beaussier, Hélène; Bézie, Yvonnick; Corny, Jennifer

2018-06-02

Background Clinical pharmacists' involvement has improved patients' care, by suggesting therapeutic optimizations. However, budget restrictions require a prioritization of these activities to focus resources on patients more at risk of medication errors. Objective The aim of our study was to identify variables influencing the formulation of pharmaceutical to improve medication review efficiency. Setting This study was conducted in medical wards of a 643-acute beds hospital in Paris, France. Methods All hospital medical prescriptions of all patients admitted within four medical wards (cardiology, rheumatology, neurology, vascular medicine) were analyzed. The study was conducted in each ward for 2 weeks, during 4 weeks. For each patient, variables prospectively collected were: age, gender, weight, emergency admission, number of high-alert medications and of total drugs prescribed, care unit, serum creatinine. Number of pharmaceutical interventions (PIs) and their type were reported. Main outcome measures Variables influencing the number of pharmaceutical interventions during medication review were identified using simple and multiple linear regressions. Results A total of 2328 drug prescriptions (303 patients, mean age 70.6 years-old) were analyzed. Mean number of hospital drug prescriptions was 7.9. A total of 318 PIs were formulated. Most frequent PIs were drug omission (n = 88, 27.7%), overdosing (n = 69, 21.7%), and underdosing (n = 51, 16.0%). Among variables studied, age, serum creatinine level, number of high-alert medications prescribed and total number of drugs prescribed were significantly associated with the formulation of pharmaceutical interventions (adjusted R 2  = 0.34). Conclusions This study identified variables (age, serum creatinine level, number of high-alert medication, number of prescribed drugs) that may help institutions/pharmacists target their reviews towards patients most likely to require pharmacist interventions.

Farmers' Perceptions of Climate Variability and Factors Influencing Adaptation: Evidence from Anhui and Jiangsu, China

NASA Astrophysics Data System (ADS)

Kibue, Grace Wanjiru; Liu, Xiaoyu; Zheng, Jufeng; zhang, Xuhui; Pan, Genxing; Li, Lianqing; Han, Xiaojun

2016-05-01

Impacts of climate variability and climate change are on the rise in China posing great threat to agriculture and rural livelihoods. Consequently, China is undertaking research to find solutions of confronting climate change and variability. However, most studies of climate change and variability in China largely fail to address farmers' perceptions of climate variability and adaptation. Yet, without an understanding of farmers' perceptions, strategies are unlikely to be effective. We conducted questionnaire surveys of farmers in two farming regions, Yifeng, Jiangsu and Qinxi, Anhui achieving 280 and 293 responses, respectively. Additionally, we used climatological data to corroborate the farmers' perceptions of climate variability. We found that farmers' were aware of climate variability such that were consistent with climate records. However, perceived impacts of climate variability differed between the two regions and were influenced by farmers' characteristics. In addition, the vast majorities of farmers were yet to make adjustments in their farming practices as a result of numerous challenges. These challenges included socioeconomic and socio-cultural barriers. Results of logit modeling showed that farmers are more likely to adapt to climate variability if contact with extension services, frequency of seeking information, household heads' education, and climate variability perceptions are improved. These results suggest the need for policy makers to understand farmers' perceptions of climate variability and change in order to formulate policies that foster adaptation, and ultimately protect China's agricultural assets.

Farmers' Perceptions of Climate Variability and Factors Influencing Adaptation: Evidence from Anhui and Jiangsu, China.

PubMed

Kibue, Grace Wanjiru; Liu, Xiaoyu; Zheng, Jufeng; Zhang, Xuhui; Pan, Genxing; Li, Lianqing; Han, Xiaojun

2016-05-01

Impacts of climate variability and climate change are on the rise in China posing great threat to agriculture and rural livelihoods. Consequently, China is undertaking research to find solutions of confronting climate change and variability. However, most studies of climate change and variability in China largely fail to address farmers' perceptions of climate variability and adaptation. Yet, without an understanding of farmers' perceptions, strategies are unlikely to be effective. We conducted questionnaire surveys of farmers in two farming regions, Yifeng, Jiangsu and Qinxi, Anhui achieving 280 and 293 responses, respectively. Additionally, we used climatological data to corroborate the farmers' perceptions of climate variability. We found that farmers' were aware of climate variability such that were consistent with climate records. However, perceived impacts of climate variability differed between the two regions and were influenced by farmers' characteristics. In addition, the vast majorities of farmers were yet to make adjustments in their farming practices as a result of numerous challenges. These challenges included socioeconomic and socio-cultural barriers. Results of logit modeling showed that farmers are more likely to adapt to climate variability if contact with extension services, frequency of seeking information, household heads' education, and climate variability perceptions are improved. These results suggest the need for policy makers to understand farmers' perceptions of climate variability and change in order to formulate policies that foster adaptation, and ultimately protect China's agricultural assets.

Dynamic characteristics of a two-stage variable-mass flexible missile with internal flow

NASA Technical Reports Server (NTRS)

Meirovitch, L.; Bankovskis, J.

1972-01-01

A general formulation of the dynamical problems associated with powered flight of a two stage flexible, variable-mass missile with internal flow, discrete masses, and aerodynamic forces is presented. The formulation comprises six ordinary differential equations for the rigid body motion, 3n ordinary differential equations for the n discrete masses and three partial differential equations with the appropriate boundary conditions for the elastic motion. This set of equations is modified to represent a single stage flexible, variable-mass missile with internal flow and aerodynamic forces. The rigid-body motion consists then of three translations and three rotations, whereas the elastic motion is defined by one longitudinal and two flexural displacements, the latter about two orthogonal transverse axes. The differential equations are nonlinear and, in addition, they possess time-dependent coefficients due to the mass variation.

Formulation and method for preparing gels comprising hydrous hafnium oxide

DOEpatents

Collins, Jack L; Hunt, Rodney D; Montgomery, Frederick C

2013-08-06

Formulations useful for preparing hydrous hafnium oxide gels contain a metal salt including hafnium, an acid, an organic base, and a complexing agent. Methods for preparing gels containing hydrous hafnium oxide include heating a formulation to a temperature sufficient to induce gel formation, where the formulation contains a metal salt including hafnium, an acid, an organic base, and a complexing agent.

A General-Purpose Optimization Engine for Multi-Disciplinary Design Applications

NASA Technical Reports Server (NTRS)

Patnaik, Surya N.; Hopkins, Dale A.; Berke, Laszlo

1996-01-01

A general purpose optimization tool for multidisciplinary applications, which in the literature is known as COMETBOARDS, is being developed at NASA Lewis Research Center. The modular organization of COMETBOARDS includes several analyzers and state-of-the-art optimization algorithms along with their cascading strategy. The code structure allows quick integration of new analyzers and optimizers. The COMETBOARDS code reads input information from a number of data files, formulates a design as a set of multidisciplinary nonlinear programming problems, and then solves the resulting problems. COMETBOARDS can be used to solve a large problem which can be defined through multiple disciplines, each of which can be further broken down into several subproblems. Alternatively, a small portion of a large problem can be optimized in an effort to improve an existing system. Some of the other unique features of COMETBOARDS include design variable formulation, constraint formulation, subproblem coupling strategy, global scaling technique, analysis approximation, use of either sequential or parallel computational modes, and so forth. The special features and unique strengths of COMETBOARDS assist convergence and reduce the amount of CPU time used to solve the difficult optimization problems of aerospace industries. COMETBOARDS has been successfully used to solve a number of problems, including structural design of space station components, design of nozzle components of an air-breathing engine, configuration design of subsonic and supersonic aircraft, mixed flow turbofan engines, wave rotor topped engines, and so forth. This paper introduces the COMETBOARDS design tool and its versatility, which is illustrated by citing examples from structures, aircraft design, and air-breathing propulsion engine design.

A three-dimensional multiphase flow model for assesing NAPL contamination in porous and fractured media, 1. Formulation

NASA Astrophysics Data System (ADS)

Huyakorn, P. S.; Panday, S.; Wu, Y. S.

1994-06-01

A three-dimensional, three-phase numerical model is presented for stimulating the movement on non-aqueous-phase liquids (NAPL's) through porous and fractured media. The model is designed for practical application to a wide variety of contamination and remediation scenarios involving light or dense NAPL's in heterogeneous subsurface systems. The model formulation is first derived for three-phase flow of water, NAPL and air (or vapor) in porous media. The formulation is then extended to handle fractured systems using the dual-porosity and discrete-fracture modeling approaches The model accommodates a wide variety of boundary conditions, including withdrawal and injection well conditions which are treated rigorously using fully implicit schemes. The three-phase of formulation collapses to its simpler forms when air-phase dynamics are neglected, capillary effects are neglected, or two-phase-air-liquid, liquid-liquid systems with one or two active phases are considered. A Galerkin procedure with upstream weighting of fluid mobilities, storage matrix lumping, and fully implicit treatment of nonlinear coefficients and well conditions is used. A variety of nodal connectivity schemes leading to finite-difference, finite-element and hybrid spatial approximations in three dimensions are incorporated in the formulation. Selection of primary variables and evaluation of the terms of the Jacobian matrix for the Newton-Raphson linearized equations is discussed. The various nodal lattice options, and their significance to the computational time and memory requirements with regards to the block-Orthomin solution scheme are noted. Aggressive time-stepping schemes and under-relaxation formulas implemented in the code further alleviate the computational burden.

Dimensional analysis of MINMOD leads to definition of the disposition index of glucose regulation and improved simulation algorithm.

PubMed

Nittala, Aparna; Ghosh, Soumitra; Stefanovski, Darko; Bergman, Richard; Wang, Xujing

2006-07-14

Frequently Sampled Intravenous Glucose Tolerance Test (FSIVGTT) together with its mathematical model, the minimal model (MINMOD), have become important clinical tools to evaluate the metabolic control of glucose in humans. Dimensional analysis of the model is up to now not available. A formal dimensional analysis of MINMOD was carried out and the degree of freedom of MINMOD was examined. Through re-expressing all state variable and parameters in terms of their reference scales, MINMOD was transformed into a dimensionless format. Previously defined physiological indices including insulin sensitivity, glucose effectiveness, and first and second phase insulin responses were re-examined in this new formulation. Further, the parameter estimation from FSIVGTT was implemented using both the dimensional and the dimensionless formulations of MINMOD, and the performances were compared utilizing Monte Carlo simulation as well as real human FSIVGTT data. The degree of freedom (DOF) of MINMOD was found to be 7. The model was maximally simplified in the dimensionless formulation that normalizes the variation in glucose and insulin during FSIVGTT. In the new formulation, the disposition index (Dl), a composite parameter known to be important in diabetes pathology, was naturally defined as one of the dimensionless parameters in the system. The numerical simulation using the dimensionless formulation led to a 1.5-5 fold gain in speed, and significantly improved accuracy and robustness in parameter estimation compared to the dimensional implementation. Dimensional analysis of MINMOD led to simplification of the model, direct identification of the important composite factors in the dynamics of glucose metabolic control, and better simulations algorithms.

Expansion of seasonal influenza vaccination in the Americas

PubMed Central

Ropero-Álvarez, Alba María; Kurtis, Hannah J; Danovaro-Holliday, M Carolina; Ruiz-Matus, Cuauhtémoc; Andrus, Jon K

2009-01-01

Background Seasonal influenza is a viral disease whose annual epidemics are estimated to cause three to five million cases of severe illness and 250,000 to 500,000 deaths worldwide. Vaccination is the main strategy for primary prevention. Methods To assess the status of influenza vaccination in the Americas, influenza vaccination data reported to the Pan American Health Organization (PAHO) through 2008 were analyzed. Results Thirty-five countries and territories administered influenza vaccine in their public health sector, compared to 13 countries in 2004. Targeted risk groups varied. Sixteen countries reported coverage among older adults, ranging from 21% to 100%; coverage data were not available for most countries and targeted populations. Some tropical countries used the Northern Hemisphere vaccine formulation and others used the Southern Hemisphere vaccine formulation. In 2008, approximately 166.3 million doses of seasonal influenza vaccine were purchased in the Americas; 30 of 35 countries procured their vaccine through PAHO's Revolving Fund. Conclusion Since 2004 there has been rapid uptake of seasonal influenza vaccine in the Americas. Challenges to fully implement influenza vaccination remain, including difficulties measuring coverage rates, variable vaccine uptake, and limited surveillance and effectiveness data to guide decisions regarding vaccine formulation and timing, especially in tropical countries. PMID:19778430

Geometry of modified release formulations during dissolution--influence on performance of dosage forms with diclofenac sodium.

PubMed

Dorożyński, Przemysław; Kulinowski, Piotr; Jamróz, Witold; Juszczyk, Ewelina

2014-12-30

The objectives of the work included: presentation of magnetic resonance imaging (MRI) and fractal analysis based approach to comparison of dosage forms of different composition, structure, and assessment of the influence of the compositional factors i.e., matrix type, excipients etc., on properties and performance of the dosage form during drug dissolution. The work presents the first attempt to compare MRI data obtained for tablet formulations of different composition and characterized by distinct differences in hydration and drug dissolution mechanisms. The main difficulty, in such a case stems from differences in hydration behavior and tablet's geometry i.e., swelling, cracking, capping etc. A novel approach to characterization of matrix systems i.e., quantification of changes of geometrical complexity of the matrix shape during drug dissolution has been developed. Using three chosen commercial modified release tablet formulations with diclofenac sodium we present the method of parameterization of their geometrical complexity on the base of fractal analysis. The main result of the study is the correlation between the hydrating tablet behavior and drug dissolution - the increase of geometrical complexity expressed as fractal dimension relates to the increased variability of drug dissolution results. Copyright © 2014 Elsevier B.V. All rights reserved.

Multi-dimensional upwinding-based implicit LES for the vorticity transport equations

NASA Astrophysics Data System (ADS)

Foti, Daniel; Duraisamy, Karthik

2017-11-01

Complex turbulent flows such as rotorcraft and wind turbine wakes are characterized by the presence of strong coherent structures that can be compactly described by vorticity variables. The vorticity-velocity formulation of the incompressible Navier-Stokes equations is employed to increase numerical efficiency. Compared to the traditional velocity-pressure formulation, high order numerical methods and sub-grid scale models for the vorticity transport equation (VTE) have not been fully investigated. Consistent treatment of the convection and stretching terms also needs to be addressed. Our belief is that, by carefully designing sharp gradient-capturing numerical schemes, coherent structures can be more efficiently captured using the vorticity-velocity formulation. In this work, a multidimensional upwind approach for the VTE is developed using the generalized Riemann problem-based scheme devised by Parish et al. (Computers & Fluids, 2016). The algorithm obtains high resolution by augmenting the upwind fluxes with transverse and normal direction corrections. The approach is investigated with several canonical vortex-dominated flows including isolated and interacting vortices and turbulent flows. The capability of the technique to represent sub-grid scale effects is also assessed. Navy contract titled ``Turbulence Modelling Across Disparate Length Scales for Naval Computational Fluid Dynamics Applications,'' through Continuum Dynamics, Inc.

QbD for pediatric oral lyophilisates development: risk assessment followed by screening and optimization.

PubMed

Casian, Tibor; Iurian, Sonia; Bogdan, Catalina; Rus, Lucia; Moldovan, Mirela; Tomuta, Ioan

2017-12-01

This study proposed the development of oral lyophilisates with respect to pediatric medicine development guidelines, by applying risk management strategies and DoE as an integrated QbD approach. Product critical quality attributes were overviewed by generating Ishikawa diagrams for risk assessment purposes, considering process, formulation and methodology related parameters. Failure Mode Effect Analysis was applied to highlight critical formulation and process parameters with an increased probability of occurrence and with a high impact on the product performance. To investigate the effect of qualitative and quantitative formulation variables D-optimal designs were used for screening and optimization purposes. Process parameters related to suspension preparation and lyophilization were classified as significant factors, and were controlled by implementing risk mitigation strategies. Both quantitative and qualitative formulation variables introduced in the experimental design influenced the product's disintegration time, mechanical resistance and dissolution properties selected as CQAs. The optimum formulation selected through Design Space presented ultra-fast disintegration time (5 seconds), a good dissolution rate (above 90%) combined with a high mechanical resistance (above 600 g load). Combining FMEA and DoE allowed the science based development of a product with respect to the defined quality target profile by providing better insights on the relevant parameters throughout development process. The utility of risk management tools in pharmaceutical development was demonstrated.

Design, formulation and optimization of valsartan transdermal gel containing iso-eucalyptol as novel permeation enhancer: preclinical assessment of pharmacokinetics in Wistar albino rats.

PubMed

Ahad, Abdul; Aqil, Mohd; Kohli, Kanchan; Sultana, Yasmin; Mujeeb, Mohd

2014-08-01

The aim of this study was to develop and optimize a transdermal gel formulation of valsartan using Box-Behnken design and to evaluate it for pharmacokinetic study. The independent variables were Carbopol 940 (X1), PEG 400 (X2) and ethanol (X3) while valsartan flux (Y1), Tlag (Y2) and gel viscosity (Y3) were the dependent variables. Iso-eucalyptol was added in all gel formulations as permeation enhancer except for control gel. It was observed that the permeation rate of valsartan significantly increased in direct proportion to the ethanol concentration, but significantly decreased in direct proportion to polymer concentration. Lag time and viscosity decreased in reverse proportion to ethanol concentration. The optimized valsartan gel formulation (VGF-OPT) yielded flux of 143.27 ± 7.11 µg/cm(2)/h and 27.55 ± 2.51 µg/cm(2)/h across rat and human cadaver skin, respectively. In vivo pharmacokinetic study of VGF-OPT-transdermal therapeutic system containing iso-eucalyptol showed a significant increase in the bioavailability (2.52 times) compared with oral formulation of valsartan by virtue of better permeation through Wistar rat skin. It was concluded that the developed transdermal gel accentuates the flux of valsartan and could be used as an antihypertensive dosage form for effective transdermal delivery of valsartan.

Comparisons of interlaboratory swellometer testing of two water-repellent preservative formulations for millwork

Treesearch

Elmer L. Schmidt; Timothy P. Murphy; Charles N. Cheeks; Alan S. Ross; T. S. (Eugene) Chiu; R. Sam Williams

2002-01-01

Water-repellency of preservative formulations used in the millwork industry has long been evaluated by measurement of the dimensional changes in wood treated and then submerged in water according to guidelines published by the millwork industry. Perceptions that this swellometer test was highly variable led to a round-robin test of one solvent-borne and one waterborne...

2D VARIABLY SATURATED FLOWS: PHYSICAL SCALING AND BAYESIAN ESTIMATION

EPA Science Inventory

A novel dimensionless formulation for water flow in two-dimensional variably saturated media is presented. It shows that scaling physical systems requires conservation of the ratio between capillary forces and gravity forces. A direct result of this finding is that for two phys...

Development and Validation of Water Vapor Tracers as Diagnostics for the Atmospheric Hydrologic Cycle

NASA Technical Reports Server (NTRS)

Bosilovich, Michael G.; Schubert, Siegfried D.; Einaudi, Franco (Technical Monitor)

2000-01-01

Understanding of the local and remote sources of water vapor can be a valuable diagnostic in understanding the regional atmospheric hydrologic cycle. In the present study, we have implemented passive tracers as prognostic variables to follow water vapor evaporated in predetermined regions until the water tracer precipitates. The formulation of the sources and sinks of tracer water is generally proportional to the prognostic water vapor variable. Because all water has been accounted for in tracers, the water vapor variable provides the validation of the tracer water and the formulation of the sources and sinks. The tracers have been implemented in a GEOS General Circulation Model (GCM) simulation consisting of several summer periods to determine the source regions of precipitation for the United States and India. The recycling of water and interannual variability of the sources of water will be examined. Potential uses in GCM sensitivity studies, predictability studies and data assimilation will be discussed.

Simulation of multivariate stationary stochastic processes using dimension-reduction representation methods

NASA Astrophysics Data System (ADS)

Liu, Zhangjun; Liu, Zenghui; Peng, Yongbo

2018-03-01

In view of the Fourier-Stieltjes integral formula of multivariate stationary stochastic processes, a unified formulation accommodating spectral representation method (SRM) and proper orthogonal decomposition (POD) is deduced. By introducing random functions as constraints correlating the orthogonal random variables involved in the unified formulation, the dimension-reduction spectral representation method (DR-SRM) and the dimension-reduction proper orthogonal decomposition (DR-POD) are addressed. The proposed schemes are capable of representing the multivariate stationary stochastic process with a few elementary random variables, bypassing the challenges of high-dimensional random variables inherent in the conventional Monte Carlo methods. In order to accelerate the numerical simulation, the technique of Fast Fourier Transform (FFT) is integrated with the proposed schemes. For illustrative purposes, the simulation of horizontal wind velocity field along the deck of a large-span bridge is proceeded using the proposed methods containing 2 and 3 elementary random variables. Numerical simulation reveals the usefulness of the dimension-reduction representation methods.

A boundary integral approach in primitive variables for free surface flows

NASA Astrophysics Data System (ADS)

Casciola, C.; Piva, R.

The boundary integral formulation, very efficient for free surface potential flows, was considered for its possible extension to rotational flows either inviscid or viscous. We first analyze a general formulation for unsteady Navier-Stokes equations in primitive variables, which reduces to a representation for the Euler equations in the limiting case of Reynolds infinity. A first simplified model for rotational flows, obtained by decoupling kinematics and dynamics, reduces the integral equations to a known kinematical form whose mathematical and numerical properties have been studied. The dynamics equations to complete the model are obtained for the free surface and the wake. A simple and efficient scheme for the study of the non linear evolution of the wave system and its interaction with the body wake is presented. A steady state version for the calculation of the wave resistance is also reported. A second model was proposed for the simulation of rotational separated regions, by coupling the integral equations in velocity with an integral equation for the vorticity at the body boundary. The same procedure may be extended to include the diffusion of the vorticity in the flowfield. The vortex shedding from a cylindrical body in unsteady motion is discussed, as a first application of the model.

Synthesis of robust nonlinear autopilots using differential game theory

NASA Technical Reports Server (NTRS)

Menon, P. K. A.

1991-01-01

A synthesis technique for handling unmodeled disturbances in nonlinear control law synthesis was advanced using differential game theory. Two types of modeling inaccuracies can be included in the formulation. The first is a bias-type error, while the second is the scale-factor-type error in the control variables. The disturbances were assumed to satisfy an integral inequality constraint. Additionally, it was assumed that they act in such a way as to maximize a quadratic performance index. Expressions for optimal control and worst-case disturbance were then obtained using optimal control theory.

Aerospace Applications of Integer and Combinatorial Optimization

NASA Technical Reports Server (NTRS)

Padula, S. L.; Kincaid, R. K.

1995-01-01

Research supported by NASA Langley Research Center includes many applications of aerospace design optimization and is conducted by teams of applied mathematicians and aerospace engineers. This paper investigates the benefits from this combined expertise in formulating and solving integer and combinatorial optimization problems. Applications range from the design of large space antennas to interior noise control. A typical problem, for example, seeks the optimal locations for vibration-damping devices on an orbiting platform and is expressed as a mixed/integer linear programming problem with more than 1500 design variables.

Aerospace applications on integer and combinatorial optimization

NASA Technical Reports Server (NTRS)

Padula, S. L.; Kincaid, R. K.

1995-01-01

Research supported by NASA Langley Research Center includes many applications of aerospace design optimization and is conducted by teams of applied mathematicians and aerospace engineers. This paper investigates the benefits from this combined expertise in formulating and solving integer and combinatorial optimization problems. Applications range from the design of large space antennas to interior noise control. A typical problem. for example, seeks the optimal locations for vibration-damping devices on an orbiting platform and is expressed as a mixed/integer linear programming problem with more than 1500 design variables.

Steady State Bioequivalence of Generic and Innovator Formulations of Stavudine, Lamivudine, and Nevirapine in HIV-Infected Ugandan Adults

PubMed Central

Byakika-Tusiime, Jayne; Chinn, Leslie W.; Oyugi, Jessica H.; Obua, Celestino; Bangsberg, David R.; Kroetz, Deanna L.

2008-01-01

Background Generic antiretroviral therapy is the mainstay of HIV treatment in resource-limited settings, yet there is little evidence confirming the bioequivalence of generic and brand name formulations. We compared the steady-state pharmacokinetics of lamivudine, stavudine and nevirapine in HIV-infected subjects who were receiving a generic formulation (Triomune®) or the corresponding brand formulations (Epivir®, Zerit®, and Viramune®). Methodology/Principal Findings An open-label, randomized, crossover study was carried out in 18 HIV-infected Ugandan subjects stabilized on Triomune-40. Subjects received lamivudine (150 mg), stavudine (40 mg), and nevirapine (200 mg) in either the generic or brand formulation twice a day for 30 days, before switching to the other formulation. At the end of each treatment period, blood samples were collected over 12 h for pharmacokinetic analysis. The main outcome measures were the mean AUC0–12h and Cmax. Bioequivalence was defined as a geometric mean ratio between the generic and brand name within the 90% confidence interval of 0.8–1.25. The geometric mean ratios and the 90% confidence intervals were: stavudine Cmax, 1.3 (0.99–1.71) and AUC0–12h, 1.1 (0.87–1.38); lamivudine Cmax, 0.8 (0.63–0.98) and AUC0–12h, 0.8 (0.65–0.99); and nevirapine Cmax, 1.1 (0.95–1.23) and AUC0–12h, 1.1 (0.95–1.31). The generic formulation was not statistically bioequivalent to the brand formulations during steady state, although exposures were comparable. A mixed random effects model identified about 50% intersubject variability in the pharmacokinetic parameters. Conclusions/Significant Findings These findings provide support for the use of Triomune in resource-limited settings, although identification of the sources of intersubject variability in these populations is critical. PMID:19096711

Formulation and optimization of coated PLGA – Zidovudine nanoparticles using factorial design and in vitro in vivo evaluations to determine brain targeting efficiency

PubMed Central

Peter Christoper, G.V.; Vijaya Raghavan, C.; Siddharth, K.; Siva Selva Kumar, M.; Hari Prasad, R.

2013-01-01

In the current study zidovudine loaded PLGA nanoparticles were prepared, coated and further investigated for its effectiveness in brain targeting. IR and DSC studies were performed to determine the interaction between excipients used and to find out the nature of drug in the formulation. Formulations were prepared by adopting 23 factorial designs to evaluate the effects of process and formulation variables. The prepared formulations were subjected for in vitro and in vivo evaluations. In vitro evaluations showed particle size below 100 nm, entrapment efficiency of formulations ranges of 28–57%, process yield of 60–76% was achieved and drug release for the formulations were in the range of 50–85%. The drug release from the formulations was found to follow Higuchi release pattern, n–value obtained after Korsemeyer plot was in the range of 0.56–0.78. In vivo evaluations were performed in mice after intraperitoneal administration of zidovudine drug solution, uncoated and coated formulation. Formulation when coated with Tween 80 achieved a higher concentration in the brain than that of the drug in solution and of the uncoated formulation. Stability studies indicated that there was no degradation of the drug in the formulation after 90 days of preparation when stored in refrigerated condition. PMID:24648825

Optimization of caseinate-coated simvastatin-zein nanoparticles: improved bioavailability and modified release characteristics.

PubMed

Ahmed, Osama A A; Hosny, Khaled M; Al-Sawahli, Majid M; Fahmy, Usama A

2015-01-01

The current study focuses on utilization of the natural biocompatible polymer zein to formulate simvastatin (SMV) nanoparticles coated with caseinate, to improve solubility and hence bioavailability, and in addition, to modify SMV-release characteristics. This formulation can be utilized for oral or possible depot parenteral applications. Fifteen formulations were prepared by liquid-liquid phase separation method, according to the Box-Behnken design, to optimize formulation variables. Sodium caseinate was used as an electrosteric stabilizer. The factors studied were: percentage of SMV in the SMV-zein mixture (X1), ethanol concentration (X2), and caseinate concentration (X3). The selected dependent variables were mean particle size (Y1), SMV encapsulation efficiency (Y2), and cumulative percentage of drug permeated after 1 hour (Y3). The diffusion of SMV from the prepared nanoparticles specified by the design was carried out using an automated Franz diffusion cell apparatus. The optimized SMV-zein formula was investigated for in vivo pharmacokinetic parameters compared with an oral SMV suspension. The optimized nanosized SMV-zein formula showed a 131 nm mean particle size and 89% encapsulation efficiency. In vitro permeation studies displayed delayed permeation characteristics, with about 42% and 85% of SMV cumulative amount released after 12 and 48 hours, respectively. Bioavailability estimation in rats revealed an augmentation in SMV bioavailability from the optimized SMV-zein formulation, by fourfold relative to SMV suspension. Formulation of caseinate-coated SMV-zein nanoparticles improves the pharmacokinetic profile and bioavailability of SMV. Accordingly, improved hypolipidemic activities for longer duration could be achieved. In addition, the reduced dosage rate of SMV-zein nanoparticles improves patient tolerability and compliance.

Mathematical modeling to predict residential solid waste generation.

PubMed

Benítez, Sara Ojeda; Lozano-Olvera, Gabriela; Morelos, Raúl Adalberto; Vega, Carolina Armijo de

2008-01-01

One of the challenges faced by waste management authorities is determining the amount of waste generated by households in order to establish waste management systems, as well as trying to charge rates compatible with the principle applied worldwide, and design a fair payment system for households according to the amount of residential solid waste (RSW) they generate. The goal of this research work was to establish mathematical models that correlate the generation of RSW per capita to the following variables: education, income per household, and number of residents. This work was based on data from a study on generation, quantification and composition of residential waste in a Mexican city in three stages. In order to define prediction models, five variables were identified and included in the model. For each waste sampling stage a different mathematical model was developed, in order to find the model that showed the best linear relation to predict residential solid waste generation. Later on, models to explore the combination of included variables and select those which showed a higher R(2) were established. The tests applied were normality, multicolinearity and heteroskedasticity. Another model, formulated with four variables, was generated and the Durban-Watson test was applied to it. Finally, a general mathematical model is proposed to predict residential waste generation, which accounts for 51% of the total.

Comparative physicochemical evaluation of a marketed herbomineral formulation: naga bhasma.

PubMed

Garg, M; Das, S; Singh, G

2012-11-01

In the practice of Ayurveda, where herbomineral formulations are said to be made biocompatible through specific processes like Shodhana and Marana, the western medical science on the contrary has raised the safety concerns of these formulations in the recent past. In the present study, comparative physico-chemical analysis of Naga bhasma, a herbo-mineral preparation having a reputation of miraculous drug commonly used to treat several health disorders, was carried out using five marketed formulations through analytical methods like differential scanning calorimetry, X-ray difraction, thermogravimetric analysis, Fourier Transform infrared spectroscopy and also subjected for particle size analysis and estimation of trace and heavy metals to access the safety of these formulation. The results revealed variable observations regarding particle size, metal form and content of lead. The presence of free lead in five different formulations indicated towards the possible risk of severe side effects to the consumer. Present findings certainly put doubt over the safety of this formulation but at the same time, variation in the results with all five formulations also indicated that these formulations were not prepared as per the mentioned Ayurvedic text. Hence, enforcement of strict regulatory guidelines is strongly warranted before launching into the market. Further, a series of biological studies need to be conducted before taking any final verdict on the safety of this formulation.

Efficacy and Safety of a Multistrain Probiotic Formulation Depends from Manufacturing.

PubMed

Trinchieri, Vito; Laghi, Luca; Vitali, Beatrice; Parolin, Carola; Giusti, Ilaria; Capobianco, Daniela; Mastromarino, Paola; De Simone, Claudio

2017-01-01

Variability in probiotics manufacturing may affect their properties, with potential implications for their efficacy and safety. This is of particular concern with probiotic products destined for use in patients with serious medical conditions, including human immunodeficiency virus (HIV) infection. The purpose of the study was to carry out a series of experiments comparing the properties of the US-made probiotic formulation originally commercialized under the brand name VSL#3 ® , with those of the Italian-made formulation now commercialized under the same name. The US-made formulation has previously shown beneficial effects at the intestinal and neurological levels in HIV-infected subjects as well as in patients with inflammatory bowel diseases and hepatic encephalopathy. Eleven subjects receiving combined antiretroviral therapy for HIV-1 were treated for 6 months with the US-made VSL#3 formulation. At baseline and 6 months, T-cells were analyzed for phenotype and activation markers, and fecal samples were analyzed for bifidobacteria, lactobacilli, and their metabolites. The fecal metabolome was assessed using 1 H-NMR spectroscopy. Production of metabolites of interest by bacteria obtained from sachets of the two formulations was compared in vitro and their effects on a rat intestinal epithelial cell line (IEC-6) were assessed. Particular attention was paid to the metabolite 1,3-dihydroxyacetone (DHA). At 6 months, fecal samples showed a significant increase in the specific bacterial genera contained in the probiotic supplement. Immune activation was reduced as shown by a significant reduction in the percentage of CD4 + CD38 + HLA-DR + T-cells at 6 months. Fecal concentrations of DHA decreased significantly. In vitro , significant differences in the production and metabolism of DHA were found between bacteria from the US-made and Italian-made formulations: the US-made formulation was able to metabolize DHA whereas the bacteria in the Italian-made formulation were producing DHA. DHA reduced the viability of Streptococcus thermophilus , reduced IEC-6 cell viability in a dose-dependent manner, and also led to a lower rate of repair to scratched IEC-6 cell monolayer. Our data, in conjunction with previously published findings, confirm that the new Italian-made formulation of VSL#3 ® is different from the previous US-made VSL#3 and therefore its efficacy and safety in HIV-infected subjects is still unproven.

Preparation and evaluation of a multimodal minoxidil microemulsion versus minoxidil alone in the treatment of androgenic alopecia of mixed etiology: a pilot study.

PubMed

Sakr, Farouk M; Gado, Ali Mi; Mohammed, Haseebur R; Adam, Abdel Nasser Ismail

2013-01-01

The variable success of topical minoxidil in the treatment of androgenic alopecia has led to the hypothesis that other pathways could mediate this form of hair loss, including infection and/or microinflammation of the hair follicles. In this study, we prepared a multimodal microemulsion comprising minoxidil (a dihydrotestosterone antagonist), diclofenac (a nonsteroidal anti-inflammatory agent), and tea tree oil (an anti-infective agent). We investigated the stability and physicochemical properties of this formulation, and its therapeutic efficacy compared with a formulation containing minoxidil alone in the treatment of androgenic alopecia. We developed a multimodal oil/water (o/w) microemulsion, a formulation containing minoxidil alone, and another containing vehicle. A three-phase diagram was constructed to obtain the optimal concentrations of the selected oil, surfactant, and cosurfactant. Thirty-two men aged 18-30 years were randomized to apply 1 mL of microemulsion containing the multimodal formulation (formulation A, n = 11), minoxidil alone (formulation B, n = 11) or placebo (formulation C, n = 10) twice daily to the affected area for 32 weeks. Efficacy was evaluated by mean hair count, thickness, and weight on the targeted area of the scalp. Global photographs were taken, changes in the area of scalp coverage were assessed by patients and external investigators, and the benefits and safety of the study medications were evaluated. The physical stability of formula A was examined after a shelf storage period of 24 months. Formulation A achieved a significantly superior response than formulations B and C in terms of mean hair count (P < 0.001), mean hair weight (P < 0.001), and mean hair thickness (P < 0.05). A patient self-assessment questionnaire demonstrated that the multimodal minoxidil formulation significantly (P < 0.001) slowed hair loss, increased hair growth, and improved appearance, and showed no appreciable side effects, such as itching and/or inflammation of the scalp compared with the minoxidil alone and placebo formulations. These improvements were in agreement with the photographic assessments made by the investigators. Formula A was shown to be an o/w formulation with consistent pH, viscosity, specific gravity, and homogeneity, and was physically stable after 24 months of normal storage. A multimodal microemulsion comprising minoxidil, diclofenac, and tea tree oil was significantly superior to minoxidil alone and placebo in terms of stability, safety, and efficacy, and achieved an earlier response in the treatment of androgenic alopecia compared with minoxidil alone in this 32-week pilot study.

Preparation and evaluation of a multimodal minoxidil microemulsion versus minoxidil alone in the treatment of androgenic alopecia of mixed etiology: a pilot study

PubMed Central

Sakr, Farouk M; Gado, Ali MI; Mohammed, Haseebur R; Adam, Abdel Nasser Ismail

2013-01-01

Background: The variable success of topical minoxidil in the treatment of androgenic alopecia has led to the hypothesis that other pathways could mediate this form of hair loss, including infection and/or microinflammation of the hair follicles. In this study, we prepared a multimodal microemulsion comprising minoxidil (a dihydrotestosterone antagonist), diclofenac (a nonsteroidal anti-inflammatory agent), and tea tree oil (an anti-infective agent). We investigated the stability and physicochemical properties of this formulation, and its therapeutic efficacy compared with a formulation containing minoxidil alone in the treatment of androgenic alopecia. Methods: We developed a multimodal oil/water (o/w) microemulsion, a formulation containing minoxidil alone, and another containing vehicle. A three-phase diagram was constructed to obtain the optimal concentrations of the selected oil, surfactant, and cosurfactant. Thirty-two men aged 18–30 years were randomized to apply 1 mL of microemulsion containing the multimodal formulation (formulation A, n = 11), minoxidil alone (formulation B, n = 11) or placebo (formulation C, n = 10) twice daily to the affected area for 32 weeks. Efficacy was evaluated by mean hair count, thickness, and weight on the targeted area of the scalp. Global photographs were taken, changes in the area of scalp coverage were assessed by patients and external investigators, and the benefits and safety of the study medications were evaluated. The physical stability of formula A was examined after a shelf storage period of 24 months. Results: Formulation A achieved a significantly superior response than formulations B and C in terms of mean hair count (P < 0.001), mean hair weight (P < 0.001), and mean hair thickness (P < 0.05). A patient self-assessment questionnaire demonstrated that the multimodal minoxidil formulation significantly (P < 0.001) slowed hair loss, increased hair growth, and improved appearance, and showed no appreciable side effects, such as itching and/or inflammation of the scalp compared with the minoxidil alone and placebo formulations. These improvements were in agreement with the photographic assessments made by the investigators. Formula A was shown to be an o/w formulation with consistent pH, viscosity, specific gravity, and homogeneity, and was physically stable after 24 months of normal storage. Conclusion: A multimodal microemulsion comprising minoxidil, diclofenac, and tea tree oil was significantly superior to minoxidil alone and placebo in terms of stability, safety, and efficacy, and achieved an earlier response in the treatment of androgenic alopecia compared with minoxidil alone in this 32-week pilot study. PMID:23807837

Thermoelastic Formulation of Stiffened, Unsymmetric Composite Panels for Finite Element Analysis of High Speed Aircraft

NASA Technical Reports Server (NTRS)

Collier, Craig S.

2004-01-01

An emerging technology need for capturing 3-D panel thermoelastic response with 2-D planar finite element models (FEMs) is aided with an equivalent plate stiffness and thermal coefficient formulation. The formulation is general and applies to all panel concepts. Included with the formulation is the ability to provide membrane-bending coupling of unsymmetric sections and calculation of all thermal expansion and bending responses from in-plane and through-the-thickness temperature gradients. Thermal residual strains for both the laminates and plies are included. The general formulation is defined and then applied to a hat-shaped, corrugated stiffened panel. Additional formulations are presented where required to include all of the hat's unique characteristics. Each formulation is validated independently with 3-D FEA.

Decision-Tree Formulation With Order-1 Lateral Execution

NASA Technical Reports Server (NTRS)

James, Mark

2007-01-01

A compact symbolic formulation enables mapping of an arbitrarily complex decision tree of a certain type into a highly computationally efficient multidimensional software object. The type of decision trees to which this formulation applies is that known in the art as the Boolean class of balanced decision trees. Parallel lateral slices of an object created by means of this formulation can be executed in constant time considerably less time than would otherwise be required. Decision trees of various forms are incorporated into almost all large software systems. A decision tree is a way of hierarchically solving a problem, proceeding through a set of true/false responses to a conclusion. By definition, a decision tree has a tree-like structure, wherein each internal node denotes a test on an attribute, each branch from an internal node represents an outcome of a test, and leaf nodes represent classes or class distributions that, in turn represent possible conclusions. The drawback of decision trees is that execution of them can be computationally expensive (and, hence, time-consuming) because each non-leaf node must be examined to determine whether to progress deeper into a tree structure or to examine an alternative. The present formulation was conceived as an efficient means of representing a decision tree and executing it in as little time as possible. The formulation involves the use of a set of symbolic algorithms to transform a decision tree into a multi-dimensional object, the rank of which equals the number of lateral non-leaf nodes. The tree can then be executed in constant time by means of an order-one table lookup. The sequence of operations performed by the algorithms is summarized as follows: 1. Determination of whether the tree under consideration can be encoded by means of this formulation. 2. Extraction of decision variables. 3. Symbolic optimization of the decision tree to minimize its form. 4. Expansion and transformation of all nested conjunctive-disjunctive paths to a flattened conjunctive form composed only of equality checks when possible. If each reduced conjunctive form contains only equality checks and all of these forms use the same variables, then the decision tree can be reduced to an order-one operation through a table lookup. The speedup to order one is accomplished by distributing each decision variable over a surface of a multidimensional object by mapping the equality constant to an index

Formulation and in vitro evaluation of xanthan gum-based bilayered mucoadhesive buccal patches of zolmitriptan.

PubMed

Shiledar, Rewathi R; Tagalpallewar, Amol A; Kokare, Chandrakant R

2014-01-30

A novel bilayered mucoadhesive buccal patch of zolmitriptan was prepared using xanthan gum (XG) as mucoadhesive polymer. Hydroxypropyl methylcellulose E-15 was used as film-former and polyvinyl alcohol (PVA) was incorporated, to increase the tensile strength of the patches. To study the effect of independent variables viz. concentrations of XG and PVA, on various dependent variables like in vitro drug release, ex vivo mucoadhesive strength and swelling index, 3(2) factorial design was employed. In vitro drug release studies of optimized formulation showed initially, rapid drug release; 43.15% within 15 min, followed by sustained release profile over 5h. Incorporation of 4% dimethyl sulfoxide enhanced drug permeability by 3.29 folds, transported 29.10% of drug after 5h and showed no buccal mucosal damage after histopathological studies. In conclusion, XG can be used as a potential drug release modifier and mucoadhesive polymer for successful formulation of zolmitriptan buccal patches. Copyright © 2013 Elsevier Ltd. All rights reserved.

How to formulate and solve "optimal stand density over time" problems for even-aged stands using dynamic programming.

Treesearch

Chung M. Chen; Dietmar W. Rose; Rolfe A. Leary

1980-01-01

Describes how dynamic programming can be used to solve optimal stand density problems when yields are given by prior simulation or by a new stand growth equation that is a function of the decision variable. Formulations of the latter type allow use of a calculus-based search procedure; they determine exact optimal residual density at each stage.

Performability modeling with continuous accomplishment sets

NASA Technical Reports Server (NTRS)

Meyer, J. F.

1979-01-01

A general modeling framework that permits the definition, formulation, and evaluation of performability is described. It is shown that performability relates directly to system effectiveness, and is a proper generalization of both performance and reliability. A hierarchical modeling scheme is used to formulate the capability function used to evaluate performability. The case in which performance variables take values in a continuous accomplishment set is treated explicitly.

Uncertain dynamical systems: A differential game approach

NASA Technical Reports Server (NTRS)

Gutman, S.

1976-01-01

A class of dynamical systems in a conflict situation is formulated and discussed, and the formulation is applied to the study of an important class of systems in the presence of uncertainty. The uncertainty is deterministic and the only assumption is that its value belongs to a known compact set. Asymptotic stability is fully discussed with application to variable structure and model reference control systems.

An ecological basis for managing giant sequoia ecosystems.

PubMed

Piirto, Douglas D; Rogers, Robert R

2002-07-01

A strategy for management of giant sequoia groves is formulated using a conceptual framework for ecosystem management recently developed by Region Five of the USDA Forest Service. The framework includes physical, biological, and social dimensions. Environmental indicators and reference variability for key ecosystem elements are discussed in this paper. The selected ecosystem elements include: 1) attitudes, beliefs, and values; 2) economics and subsistence; 3) stream channel morphology; 4) sediment; 5) water; 6) fire; 7) organic debris; and 8) vegetation mosaic. Recommendations are made for the attributes of environmental indicators that characterize these elements. These elements and associated indicators will define and control management activities for the protection, preservation, and restoration of national forest giant sequoia ecosystems.

Advance finite element modeling of rotor blade aeroelasticity

NASA Technical Reports Server (NTRS)

Straub, F. K.; Sangha, K. B.; Panda, B.

1994-01-01

An advanced beam finite element has been developed for modeling rotor blade dynamics and aeroelasticity. This element is part of the Element Library of the Second Generation Comprehensive Helicopter Analysis System (2GCHAS). The element allows modeling of arbitrary rotor systems, including bearingless rotors. It accounts for moderately large elastic deflections, anisotropic properties, large frame motion for maneuver simulation, and allows for variable order shape functions. The effects of gravity, mechanically applied and aerodynamic loads are included. All kinematic quantities required to compute airloads are provided. In this paper, the fundamental assumptions and derivation of the element matrices are presented. Numerical results are shown to verify the formulation and illustrate several features of the element.

Digital program for solving the linear stochastic optimal control and estimation problem

NASA Technical Reports Server (NTRS)

Geyser, L. C.; Lehtinen, B.

1975-01-01

A computer program is described which solves the linear stochastic optimal control and estimation (LSOCE) problem by using a time-domain formulation. The LSOCE problem is defined as that of designing controls for a linear time-invariant system which is disturbed by white noise in such a way as to minimize a performance index which is quadratic in state and control variables. The LSOCE problem and solution are outlined; brief descriptions are given of the solution algorithms, and complete descriptions of each subroutine, including usage information and digital listings, are provided. A test case is included, as well as information on the IBM 7090-7094 DCS time and storage requirements.

The Grassmannian origin of dual superconformal invariance

NASA Astrophysics Data System (ADS)

Arkani-Hamed, Nima; Cachazo, Freddy; Cheung, Clifford

2010-03-01

A dual formulation of the S Matrix for mathcal {N} = 4 SYM has recently been presented, where all leading singularities of n-particle N k-2MHV amplitudes are given as an integral over the Grassmannian G( k, n), with cyclic symmetry, parity and superconformal invariance manifest. In this short note we show that the dual superconformal invariance of this object is also manifest. The geometry naturally suggests a partial integration and simple change of variable to an integral over G( k - 2, n). This change of variable precisely corresponds to the mapping between usual momentum variables and the “momentum twistors” introduced by Hodges, and yields an elementary derivation of the momentumtwistor space formula very recently presented by Mason and Skinner, which is manifestly dual superconformal invariant. Thus the G( k, n) Grassmannian formulation allows a direct understanding of all the important symmetries of mathcal {N} = 4 SYM scattering amplitudes.

A multiscale model for reinforced concrete with macroscopic variation of reinforcement slip

NASA Astrophysics Data System (ADS)

Sciegaj, Adam; Larsson, Fredrik; Lundgren, Karin; Nilenius, Filip; Runesson, Kenneth

2018-06-01

A single-scale model for reinforced concrete, comprising the plain concrete continuum, reinforcement bars and the bond between them, is used as a basis for deriving a two-scale model. The large-scale problem, representing the "effective" reinforced concrete solid, is enriched by an effective reinforcement slip variable. The subscale problem on a Representative Volume Element (RVE) is defined by Dirichlet boundary conditions. The response of the RVEs of different sizes was investigated by means of pull-out tests. The resulting two-scale formulation was used in an FE^2 analysis of a deep beam. Load-deflection relations, crack widths, and strain fields were compared to those obtained from a single-scale analysis. Incorporating the independent macroscopic reinforcement slip variable resulted in a more pronounced localisation of the effective strain field. This produced a more accurate estimation of the crack widths than the two-scale formulation neglecting the effective reinforcement slip variable.

Sports Participation and Social Personality Variable of Students in Secondary Schools in Central Senatorial District of Cross River State, Nigeria

ERIC Educational Resources Information Center

Edim, M. E.; Odok, E. A.

2015-01-01

The main thrust of this study was to investigate sports participation and social personality variable of students in secondary schools in Central Senatorial District of Cross River State, Nigeria. To achieve the purpose of this study, one hypothesis was formulated to guide the study. Literature review was carried out according to the variable of…

New variables for classical and quantum gravity

NASA Technical Reports Server (NTRS)

Ashtekar, Abhay

1986-01-01

A Hamiltonian formulation of general relativity based on certain spinorial variables is introduced. These variables simplify the constraints of general relativity considerably and enable one to imbed the constraint surface in the phase space of Einstein's theory into that of Yang-Mills theory. The imbedding suggests new ways of attacking a number of problems in both classical and quantum gravity. Some illustrative applications are discussed.

Spinor matter fields in SL(2,C) gauge theories of gravity: Lagrangian and Hamiltonian approaches

NASA Astrophysics Data System (ADS)

Antonowicz, Marek; Szczyrba, Wiktor

1985-06-01

We consider the SL(2,C)-covariant Lagrangian formulation of gravitational theories with the presence of spinor matter fields. The invariance properties of such theories give rise to the conservation laws (the contracted Bianchi identities) having in the presence of matter fields a more complicated form than those known in the literature previously. A general SL(2,C) gauge theory of gravity is cast into an SL(2,C)-covariant Hamiltonian formulation. Breaking the SL(2,C) symmetry of the system to the SU(2) symmetry, by introducing a spacelike slicing of spacetime, we get an SU(2)-covariant Hamiltonian picture. The qualitative analysis of SL(2,C) gauge theories of gravity in the SU(2)-covariant formulation enables us to define the dynamical symplectic variables and the gauge variables of the theory under consideration as well as to divide the set of field equations into the dynamical equations and the constraints. In the SU(2)-covariant Hamiltonian formulation the primary constraints, which are generic for first-order matter Lagrangians (Dirac, Weyl, Fierz-Pauli), can be reduced. The effective matter symplectic variables are given by SU(2)-spinor-valued half-forms on three-dimensional slices of spacetime. The coupled Einstein-Cartan-Dirac (Weyl, Fierz-Pauli) system is analyzed from the (3+1) point of view. This analysis is complete; the field equations of the Einstein-Cartan-Dirac theory split into 18 gravitational dynamical equations, 8 dynamical Dirac equations, and 7 first-class constraints. The system has 4+8=12 independent degrees of freedom in the phase space.

Formulation, in vitro evaluation and study of variables on tri-layered gastro-retentive delivery system of diltiazem HCl.

PubMed

Raut Desai, Shilpa; Rohera, Bhagwan D

2014-03-01

Tri-layered floating tablets using only one grade of polyethylene oxide (PEO) would enable easy manufacturing, reproducibility and controlled release for highly soluble drugs. To evaluate the potential of PEO as a sole polymer for the controlled release and to study the effect of formulation variables on release and gastric retention of highly soluble Diltiazem hydrochloride (DTZ). Tablets were compressed with middle layer consisting of drug and polymer while outer layers consisted of polymer with sodium bicarbonate. Design of formulation to obtain 12 h, zero-order release and rapid floatation was done by varying the grades, quantity of PEO and sodium bicarbonate. Dissolution data were fitted in drug release models and swelling/erosion studies were undertaken to verify the drug release mechanism. Effect of formulation variables and tablet surface morphology using scanning electron microscopy were studied. The optimized formula passed the criteria of USP dissolution test I and exhibited floating lag-time of 3-4 min. Drug release was faster from low molecular weight (MW) PEO as compared to high MW. With an increase in the amount of sodium bicarbonate, faster buoyancy was achieved due to the increased CO2 gas formation. Drug release followed zero-order and gave a good fit to the Korsmeyer-Peppas model, which suggested that drug release was due to diffusion through polymer swelling. Zero-order, controlled release profile with the desired buoyancy can be achieved by using optimum formula quantities of sodium bicarbonate and polymer. The tri-layered system shows promising delivery of DTZ, and possibly other water-soluble drugs.

Formulation design for optimal high-shear wet granulation using on-line torque measurements.

PubMed

Cavinato, Mauro; Bresciani, Massimo; Machin, Marianna; Bellazzi, Guido; Canu, Paolo; Santomaso, Andrea C

2010-03-15

An alternative procedure for achieving formulation design in a high-shear wet granulation process has been developed. Particularly, a new formulation map has been proposed which describes the onset of a significant granule growth as a function of the formulation variables (diluent, dry and liquid binder). Granule growth has been monitored using on-line impeller torque and evaluated as changes in granule particle size distribution with respect to the dry formulation. It is shown how the onset of granule growth is denoted by an abrupt increase in the torque value requires the amount of binder liquid added to be greater than a certain threshold that is identified here as 'minimum liquid volume'. This minimum liquid volume is determined as a function of dry binder type, amount, hygroscopicity and particle size distribution of diluent. It is also demonstrated how this formulation map can be constructed from independent measurements of binder glass transition temperatures using a static humidity conditioning system. 2009 Elsevier B.V. All rights reserved.

Encapsulation Processing and Manufacturing Yield Analysis

NASA Technical Reports Server (NTRS)

Willis, P. B.

1984-01-01

The development of encapsulation processing and a manufacturing productivity analysis for photovoltaic cells are discussed. The goals were: (1) to understand the relationships between both formulation variables and process variables; (2) to define conditions required for optimum performance; (3) to predict manufacturing yield; and (4) to provide documentation to industry.

Encapsulation processing and manufacturing yield analysis

NASA Astrophysics Data System (ADS)

Willis, P. B.

1984-10-01

The development of encapsulation processing and a manufacturing productivity analysis for photovoltaic cells are discussed. The goals were: (1) to understand the relationships between both formulation variables and process variables; (2) to define conditions required for optimum performance; (3) to predict manufacturing yield; and (4) to provide documentation to industry.

Effects of the Approval Motive Upon Resistance to Temptation Under Contrasting Incentive Conditions.

ERIC Educational Resources Information Center

Nelsen, Edward A.; And Others

This paper describes a study which examined interactive relationships between a personality variable (need for approval) and a situational variable (incentive for achievement) as determinants of transgression in temptation situations. Hypotheses were formulated that need for approval would correlate differentially with transgression when…

Coupled variational formulations of linear elasticity and the DPG methodology

NASA Astrophysics Data System (ADS)

Fuentes, Federico; Keith, Brendan; Demkowicz, Leszek; Le Tallec, Patrick

2017-11-01

This article presents a general approach akin to domain-decomposition methods to solve a single linear PDE, but where each subdomain of a partitioned domain is associated to a distinct variational formulation coming from a mutually well-posed family of broken variational formulations of the original PDE. It can be exploited to solve challenging problems in a variety of physical scenarios where stability or a particular mode of convergence is desired in a part of the domain. The linear elasticity equations are solved in this work, but the approach can be applied to other equations as well. The broken variational formulations, which are essentially extensions of more standard formulations, are characterized by the presence of mesh-dependent broken test spaces and interface trial variables at the boundaries of the elements of the mesh. This allows necessary information to be naturally transmitted between adjacent subdomains, resulting in coupled variational formulations which are then proved to be globally well-posed. They are solved numerically using the DPG methodology, which is especially crafted to produce stable discretizations of broken formulations. Finally, expected convergence rates are verified in two different and illustrative examples.

Modeling of the Mode S tracking system in support of aircraft safety research

NASA Technical Reports Server (NTRS)

Sorensen, J. A.; Goka, T.

1982-01-01

This report collects, documents, and models data relating the expected accuracies of tracking variables to be obtained from the FAA's Mode S Secondary Surveillance Radar system. The data include measured range and azimuth to the tracked aircraft plus the encoded altitude transmitted via the Mode S data link. A brief summary is made of the Mode S system status and its potential applications for aircraft safety improvement including accident analysis. FAA flight test results are presented demonstrating Mode S range and azimuth accuracy and error characteristics and comparing Mode S to the current ATCRBS radar tracking system. Data are also presented that describe the expected accuracy and error characteristics of encoded altitude. These data are used to formulate mathematical error models of the Mode S variables and encoded altitude. A brief analytical assessment is made of the real-time tracking accuracy available from using Mode S and how it could be improved with down-linked velocity.

Flap-lag-torsional dynamic modelling of rotor blades in hover and in forward flight, including the effect of cubic nonlinearities

NASA Technical Reports Server (NTRS)

Crespodasilva, M. R. M.

1981-01-01

The differential equations of motion, and boundary conditions, describing the flap-lead/lag-torsional motion of a flexible rotor blade with a precone angle and a variable pitch angle, which incorporates a pretwist, are derived via Hamilton's principle. The meaning of inextensionality is discussed. The equations are reduced to a set of three integro partial differential equations by elimination of the extension variable. The generalized aerodynamic forces are modelled using Greenberg's extension of Theodorsen's strip theory. The equations of motion are systematically expanded into polynomial nonlinearities with the objective of retaining all terms up to third degree. The blade is modeled as a long, slender, of isotropic Hookean materials. Offsets from the blade's elastic axis through its shear center and the axes for the mass, area and aerodynamic centers, radial nonuniformaties of the blade's stiffnesses and cross section properties are considered and the effect of warp of the cross section is included in the formulation.

Optimal control in microgrid using multi-agent reinforcement learning.

PubMed

Li, Fu-Dong; Wu, Min; He, Yong; Chen, Xin

2012-11-01

This paper presents an improved reinforcement learning method to minimize electricity costs on the premise of satisfying the power balance and generation limit of units in a microgrid with grid-connected mode. Firstly, the microgrid control requirements are analyzed and the objective function of optimal control for microgrid is proposed. Then, a state variable "Average Electricity Price Trend" which is used to express the most possible transitions of the system is developed so as to reduce the complexity and randomicity of the microgrid, and a multi-agent architecture including agents, state variables, action variables and reward function is formulated. Furthermore, dynamic hierarchical reinforcement learning, based on change rate of key state variable, is established to carry out optimal policy exploration. The analysis shows that the proposed method is beneficial to handle the problem of "curse of dimensionality" and speed up learning in the unknown large-scale world. Finally, the simulation results under JADE (Java Agent Development Framework) demonstrate the validity of the presented method in optimal control for a microgrid with grid-connected mode. Copyright © 2012 ISA. Published by Elsevier Ltd. All rights reserved.

An interactive approach based on a discrete differential evolution algorithm for a class of integer bilevel programming problems

NASA Astrophysics Data System (ADS)

Li, Hong; Zhang, Li; Jiao, Yong-Chang

2016-07-01

This paper presents an interactive approach based on a discrete differential evolution algorithm to solve a class of integer bilevel programming problems, in which integer decision variables are controlled by an upper-level decision maker and real-value or continuous decision variables are controlled by a lower-level decision maker. Using the Karush--Kuhn-Tucker optimality conditions in the lower-level programming, the original discrete bilevel formulation can be converted into a discrete single-level nonlinear programming problem with the complementarity constraints, and then the smoothing technique is applied to deal with the complementarity constraints. Finally, a discrete single-level nonlinear programming problem is obtained, and solved by an interactive approach. In each iteration, for each given upper-level discrete variable, a system of nonlinear equations including the lower-level variables and Lagrange multipliers is solved first, and then a discrete nonlinear programming problem only with inequality constraints is handled by using a discrete differential evolution algorithm. Simulation results show the effectiveness of the proposed approach.

Optimization of edible coating formulations for improving postharvest quality and shelf life of pear fruit using response surface methodology.

PubMed

Nandane, A S; Dave, Rudri K; Rao, T V Ramana

2017-01-01

The effect of composite edible films containing soy protein isolate (SPI) in combination with additives like hydroxypropyl methylcellulose (HPMC) and olive oil on 'Babughosha' pear ( Pyrus communis L.) stored at ambient temperature (28 ± 5 °C and 60 ± 10% RH) was evaluated using Response surface methodology (RSM). A total of 30 edible coating formulations comprising of SPI (2-6%, w/v), olive oil (0.7-1.1%, v/v), HPMC (0.1-0.5%, w/v) and potassium sorbate (0-0.4% w/v) were evaluated for optimizing the most suitable combination. Quality parameters like weight loss%, TSS, pH and titrable acidity of the stored pears were selected as response variables for optimization. The optimization procedure was carried out using RSM. It was observed that the response variables were mainly effected by concentration of SPI and olive oil in the formulation. Edible coating comprising of SPI 5%, HPMC 0.40%, olive oil 1% and potassium sorbate 0.22% was found to be most suitable combination for pear fruit with predicted values of response variables indicated as weight loss% 3.50, pH 3.41, TSS 11.13 and TA% 0.513.

Development of an ANN optimized mucoadhesive buccal tablet containing flurbiprofen and lidocaine for dental pain.

PubMed

Hussain, Amjad; Syed, Muhammad Ali; Abbas, Nasir; Hanif, Sana; Arshad, Muhammad Sohail; Bukhari, Nadeem Irfan; Hussain, Khalid; Akhlaq, Muhammad; Ahmad, Zeeshan

2016-06-01

A novel mucoadhesive buccal tablet containing flurbiprofen (FLB) and lidocaine HCl (LID) was prepared to relieve dental pain. Tablet formulations (F1-F9) were prepared using variable quantities of mucoadhesive agents, hydroxypropyl methyl cellulose (HPMC) and sodium alginate (SA). The formulations were evaluated for their physicochemical properties, mucoadhesive strength and mucoadhesion time, swellability index and in vitro release of active agents. Release of both drugs depended on the relative ratio of HPMC:SA. However, mucoadhesive strength and mucoadhesion time were better in formulations, containing higher proportions of HPMC compared to SA. An artificial neural network (ANN) approach was applied to optimise formulations based on known effective parameters (i.e., mucoadhesive strength, mucoadhesion time and drug release), which proved valuable. This study indicates that an effective buccal tablet formulation of flurbiprofen and lidocaine can be prepared via an optimized ANN approach.

[New developments in extemporaneous formulations].

PubMed

Staubach, P; Melhorn, S; Hünerbein, A; Peveling-Oberhag, A

2016-10-01

Dermatology is in a state of flux, and systemic therapies have changed the prescription practice in the past few years. Nevertheless, topical therapy for dermatological illnesses is still the mainstay of dermatologists. Pharmaceutically manufactured drugs have a wide spectrum and allow for variability. Additionally, there are therapeutic niches that can be bridged by prescribing extemporaneous formulations. This is also true for the newly established basic therapies for many chronic dermatological illnesses which have become essential and are needed in large amounts. Unfortunately, neither during medical school, nor during residency training, not even the basic knowledge or the complexity of these extemporaneous formulations for topical therapy in dermatology is taught. This emphasizes why standardized, proven extemporaneous formulations are vital for physicians to achieve optimal and goal-oriented therapy for their patients. Sensible and effective prescriptions enhance the quality of formulations and the maintenance and well-being of our patients.

Cartan gravity, matter fields, and the gauge principle

DOE Office of Scientific and Technical Information (OSTI.GOV)

Westman, Hans F., E-mail: hwestman74@gmail.com; Zlosnik, Tom G., E-mail: t.zlosnik@imperial.ac.uk

Gravity is commonly thought of as one of the four force fields in nature. However, in standard formulations its mathematical structure is rather different from the Yang–Mills fields of particle physics that govern the electromagnetic, weak, and strong interactions. This paper explores this dissonance with particular focus on how gravity couples to matter from the perspective of the Cartan-geometric formulation of gravity. There the gravitational field is represented by a pair of variables: (1) a ‘contact vector’ V{sup A} which is geometrically visualized as the contact point between the spacetime manifold and a model spacetime being ‘rolled’ on top ofmore » it, and (2) a gauge connection A{sub μ}{sup AB}, here taken to be valued in the Lie algebra of SO(2,3) or SO(1,4), which mathematically determines how much the model spacetime is rotated when rolled. By insisting on two principles, the gauge principle and polynomial simplicity, we shall show how one can reformulate matter field actions in a way that is harmonious with Cartan’s geometric construction. This yields a formulation of all matter fields in terms of first order partial differential equations. We show in detail how the standard second order formulation can be recovered. In particular, the Hodge dual, which characterizes the structure of bosonic field equations, pops up automatically. Furthermore, the energy–momentum and spin-density three-forms are naturally combined into a single object here denoted the spin-energy–momentum three-form. Finally, we highlight a peculiarity in the mathematical structure of our first-order formulation of Yang–Mills fields. This suggests a way to unify a U(1) gauge field with gravity into a SO(1,5)-valued gauge field using a natural generalization of Cartan geometry in which the larger symmetry group is spontaneously broken down to SO(1,3)×U(1). The coupling of this unified theory to matter fields and possible extensions to non-Abelian gauge fields are left as open questions. -- Highlights: •Develops Cartan gravity to include matter fields. •Coupling to gravity is done using the standard gauge prescription. •Matter actions are manifestly polynomial in all field variables. •Standard equations recovered on-shell for scalar, spinor and Yang–Mills fields. •Unification of a U(1) field with gravity based on the orthogonal group SO(1,5)« less

The Madrid Affective Database for Spanish (MADS): Ratings of Dominance, Familiarity, Subjective Age of Acquisition and Sensory Experience

PubMed Central

Hinojosa, José A.; Rincón-Pérez, Irene; Romero-Ferreiro, Mª Verónica; Martínez-García, Natalia; Villalba-García, Cristina; Montoro, Pedro R.; Pozo, Miguel A.

2016-01-01

The current study presents ratings by 540 Spanish native speakers for dominance, familiarity, subjective age of acquisition (AoA), and sensory experience (SER) for the 875 Spanish words included in the Madrid Affective Database for Spanish (MADS). The norms can be downloaded as supplementary materials for this manuscript from https://figshare.com/s/8e7b445b729527262c88 These ratings may be of potential relevance to researches who are interested in characterizing the interplay between language and emotion. Additionally, with the aim of investigating how the affective features interact with the lexicosemantic properties of words, we performed correlational analyses between norms for familiarity, subjective AoA and SER, and scores for those affective variables which are currently included in the MADs. A distinct pattern of significant correlations with affective features was found for different lexicosemantic variables. These results show that familiarity, subjective AoA and SERs may have independent effects on the processing of emotional words. They also suggest that these psycholinguistic variables should be fully considered when formulating theoretical approaches to the processing of affective language. PMID:27227521

Conservative-variable average states for equilibrium gas multi-dimensional fluxes

NASA Technical Reports Server (NTRS)

Iannelli, G. S.

1992-01-01

Modern split component evaluations of the flux vector Jacobians are thoroughly analyzed for equilibrium-gas average-state determinations. It is shown that all such derivations satisfy a fundamental eigenvalue consistency theorem. A conservative-variable average state is then developed for arbitrary equilibrium-gas equations of state and curvilinear-coordinate fluxes. Original expressions for eigenvalues, sound speed, Mach number, and eigenvectors are then determined for a general average Jacobian, and it is shown that the average eigenvalues, Mach number, and eigenvectors may not coincide with their classical pointwise counterparts. A general equilibrium-gas equation of state is then discussed for conservative-variable computational fluid dynamics (CFD) Euler formulations. The associated derivations lead to unique compatibility relations that constrain the pressure Jacobian derivatives. Thereafter, alternative forms for the pressure variation and average sound speed are developed in terms of two average pressure Jacobian derivatives. Significantly, no additional degree of freedom exists in the determination of these two average partial derivatives of pressure. Therefore, they are simultaneously computed exactly without any auxiliary relation, hence without any geometric solution projection or arbitrary scale factors. Several alternative formulations are then compared and key differences highlighted with emphasis on the determination of the pressure variation and average sound speed. The relevant underlying assumptions are identified, including some subtle approximations that are inherently employed in published average-state procedures. Finally, a representative test case is discussed for which an intrinsically exact average state is determined. This exact state is then compared with the predictions of recent methods, and their inherent approximations are appropriately quantified.

Variable strategy model of the human operator

NASA Astrophysics Data System (ADS)

Phillips, John Michael

Human operators often employ discontinuous or "bang-bang" control strategies when performing large-amplitude acquisition tasks. The current study applies Variable Structure Control (VSC) techniques to model human operator behavior during acquisition tasks. The result is a coupled, multi-input model replicating the discontinuous control strategy. In the VSC formulation, a switching surface is the mathematical representation of the operator's control strategy. The performance of the Variable Strategy Model (VSM) is evaluated by considering several examples, including the longitudinal control of an aircraft during the visual landing task. The aircraft landing task becomes an acquisition maneuver whenever large initial offsets occur. Several different strategies are explored in the VSM formulation for the aircraft landing task. First, a switching surface is constructed from literal interpretations of pilot training literature. This approach yields a mathematical representation of how a pilot is trained to fly a generic aircraft. This switching surface is shown to bound the trajectory response of a group of pilots performing an offset landing task in an aircraft simulator study. Next, front-side and back-side landing strategies are compared. A back-side landing strategy is found to be capable of landing an aircraft flying on either the front side or back side of the power curve. However, the front-side landing strategy is found to be insufficient for landing an aircraft flying on the back side. Finally, a more refined landing strategy is developed that takes into the account the specific aircraft's dynamic characteristics. The refined strategy is translated back into terminology similar to the existing pilot training literature.

FRAMEWORK FOR ASSESSING RISKS OF ...

EPA Pesticide Factsheets

The Framework for Children's Health Risk Assessment report can serve as a resource on children's health risk assessment and it addresses the need to provide a comprehensive and consistent framework for considering children in risk assessments at EPA. This framework lays out the process, points to existing published sources for more detailed information on life stage-specific considerations, and includes web links to specific online publications and relevant Agency science policy papers, guidelines and guidance. The document emphasizes the need to take into account the potential exposures to environmental agents during preconception and all stages of development and focuses on the relevant adverse health outcomes that may occur as a result of such exposures. This framework is not an Agency guideline, but rather describes the overall structure and the components considered important for children's health risk assessment. The document describes an approach that includes problem formulation, analysis, and risk characterization, and also builds on Agency experience assessing risk to susceptible populations. The problem formulation step focuses on the life stage-specific nature of the analysis to include scoping and screening level questions for hazard characterization, dose response and exposure assessment. The risk characterization step recognizes the need to consider life stage-specific risks and explicitly describes the uncertainties and variability in the d

Multi-objective trajectory optimization for the space exploration vehicle

NASA Astrophysics Data System (ADS)

Qin, Xiaoli; Xiao, Zhen

2016-07-01

The research determines temperature-constrained optimal trajectory for the space exploration vehicle by developing an optimal control formulation and solving it using a variable order quadrature collocation method with a Non-linear Programming(NLP) solver. The vehicle is assumed to be the space reconnaissance aircraft that has specified takeoff/landing locations, specified no-fly zones, and specified targets for sensor data collections. A three degree of freedom aircraft model is adapted from previous work and includes flight dynamics, and thermal constraints.Vehicle control is accomplished by controlling angle of attack, roll angle, and propellant mass flow rate. This model is incorporated into an optimal control formulation that includes constraints on both the vehicle and mission parameters, such as avoidance of no-fly zones and exploration of space targets. In addition, the vehicle models include the environmental models(gravity and atmosphere). How these models are appropriately employed is key to gaining confidence in the results and conclusions of the research. Optimal trajectories are developed using several performance costs in the optimal control formation,minimum time,minimum time with control penalties,and maximum distance.The resulting analysis demonstrates that optimal trajectories that meet specified mission parameters and constraints can be quickly determined and used for large-scale space exloration.

Automatic design of basin-specific drought indexes for highly regulated water systems

NASA Astrophysics Data System (ADS)

Zaniolo, Marta; Giuliani, Matteo; Castelletti, Andrea Francesco; Pulido-Velazquez, Manuel

2018-04-01

Socio-economic costs of drought are progressively increasing worldwide due to undergoing alterations of hydro-meteorological regimes induced by climate change. Although drought management is largely studied in the literature, traditional drought indexes often fail at detecting critical events in highly regulated systems, where natural water availability is conditioned by the operation of water infrastructures such as dams, diversions, and pumping wells. Here, ad hoc index formulations are usually adopted based on empirical combinations of several, supposed-to-be significant, hydro-meteorological variables. These customized formulations, however, while effective in the design basin, can hardly be generalized and transferred to different contexts. In this study, we contribute FRIDA (FRamework for Index-based Drought Analysis), a novel framework for the automatic design of basin-customized drought indexes. In contrast to ad hoc empirical approaches, FRIDA is fully automated, generalizable, and portable across different basins. FRIDA builds an index representing a surrogate of the drought conditions of the basin, computed by combining all the relevant available information about the water circulating in the system identified by means of a feature extraction algorithm. We used the Wrapper for Quasi-Equally Informative Subset Selection (W-QEISS), which features a multi-objective evolutionary algorithm to find Pareto-efficient subsets of variables by maximizing the wrapper accuracy, minimizing the number of selected variables, and optimizing relevance and redundancy of the subset. The preferred variable subset is selected among the efficient solutions and used to formulate the final index according to alternative model structures. We apply FRIDA to the case study of the Jucar river basin (Spain), a drought-prone and highly regulated Mediterranean water resource system, where an advanced drought management plan relying on the formulation of an ad hoc state index is used for triggering drought management measures. The state index was constructed empirically with a trial-and-error process begun in the 1980s and finalized in 2007, guided by the experts from the Confederación Hidrográfica del Júcar (CHJ). Our results show that the automated variable selection outcomes align with CHJ's 25-year-long empirical refinement. In addition, the resultant FRIDA index outperforms the official State Index in terms of accuracy in reproducing the target variable and cardinality of the selected inputs set.

Performance of mixed formulations for the particle finite element method in soil mechanics problems

NASA Astrophysics Data System (ADS)

Monforte, Lluís; Carbonell, Josep Maria; Arroyo, Marcos; Gens, Antonio

2017-07-01

This paper presents a computational framework for the numerical analysis of fluid-saturated porous media at large strains. The proposal relies, on one hand, on the particle finite element method (PFEM), known for its capability to tackle large deformations and rapid changing boundaries, and, on the other hand, on constitutive descriptions well established in current geotechnical analyses (Darcy's law; Modified Cam Clay; Houlsby hyperelasticity). An important feature of this kind of problem is that incompressibility may arise either from undrained conditions or as a consequence of material behaviour; incompressibility may lead to volumetric locking of the low-order elements that are typically used in PFEM. In this work, two different three-field mixed formulations for the coupled hydromechanical problem are presented, in which either the effective pressure or the Jacobian are considered as nodal variables, in addition to the solid skeleton displacement and water pressure. Additionally, several mixed formulations are described for the simplified single-phase problem due to its formal similitude to the poromechanical case and its relevance in geotechnics, since it may approximate the saturated soil behaviour under undrained conditions. In order to use equal-order interpolants in displacements and scalar fields, stabilization techniques are used in the mass conservation equation of the biphasic medium and in the rest of scalar equations. Finally, all mixed formulations are assessed in some benchmark problems and their performances are compared. It is found that mixed formulations that have the Jacobian as a nodal variable perform better.

Terbinafine Hydrochloride Trans-ungual Delivery via Nanovesicular Systems: In Vitro Characterization and Ex Vivo Evaluation.

PubMed

Elsherif, Noha Ibrahim; Shamma, Rehab Nabil; Abdelbary, Ghada

2017-02-01

Treating a nail infection like onychomycosis is challenging as the human nail plate acts as a formidable barrier against all drug permeation. Available oral and topical treatments have several setbacks. Terbinafine hydrochloride (TBH), belonging to the allylamine class, is mainly used for treatment of onychomycosis. This study aims to formulate TBH in a nanobased spanlastic vesicular carrier that enables and enhances the drug delivery through the nail. The nanovesicles were formulated by ethanol injection method, using either Span® 60 or Span® 65, together with Tween 80 or sodium deoxycholate as an edge activator. A full factorial design was implemented to study the effect of different formulation and process variables on the prepared TBH-loaded spanlastic nanovesicles. TBH entrapment efficiency percentages, particle size diameter, percentage drug released after 2 h and 8 h were selected as dependent variables. Optimization was performed using Design-Expert® software to obtain an optimized formulation with high entrapment efficiency (62.35 ± 8.91%), average particle size of 438.45 ± 70.5 nm, and 29.57 ± 0.93 and 59.53 ± 1.73% TBH released after 2 and 8 h, respectively. The optimized formula was evaluated using differential scanning calorimetry and X-ray diffraction and was also morphologically examined using transmission electron microscopy. An ex vivo study was conducted to determine the permeation and retainment of the optimized formulation in a human cadaver nail plate, and confocal laser scanning microscope was used to show the extent of formulation permeation. In conclusion, the results confirmed that spanlastics exhibit promising results for the trans-ungual delivery of TBH.

The impact of new partial AUC parameters for evaluating the bioequivalence of prolonged-release formulations.

PubMed

Boily, Michaël; Dussault, Catherine; Massicotte, Julie; Guibord, Pascal; Lefebvre, Marc

2015-01-23

To demonstrate bioequivalence (BE) between two prolonged-release (PR) drug formulations, single dose studies under fasting and fed state as well as at least one steady-state study are currently required by the European Medicines Agency (EMA). Recently, however, there have been debates regarding the relevance of steady-state studies. New requirements in single-dose investigations have also been suggested by the EMA to address the absence of a parameter that can adequately assess the equivalence of the shape of the curves. In the draft guideline issued in 2013, new partial area under the curve (pAUC) pharmacokinetic (PK) parameters were introduced to that effect. In light of these potential changes, there is a need of supportive clinical evidence to evaluate the impact of pAUCs on the evaluation of BE between PR formulations. In this retrospective analysis, it was investigated whether the newly defined parameters were associated with an increase in discriminatory ability or a change in variability compared to the conventional PK parameters. Among the single dose studies that met the requirements already in place, 20% were found unable to meet the EMA's new requirements in regards to the pAUC PK parameters. When pairing fasting and fed studies for a same formulation, the failure rate increased to 40%. In some cases, due to the high variability of these parameters, an increase of the sample size would be required to prove BE. In other cases however, the pAUC parameters demonstrated a robust ability to detect differences between the shapes of the curves of PR formulations. The present analysis should help to better understand the impact of the upcoming changes in European regulations on PR formulations and in the design of future BE studies. Copyright © 2014 Elsevier B.V. All rights reserved.

Optimization of caseinate-coated simvastatin-zein nanoparticles: improved bioavailability and modified release characteristics

PubMed Central

Ahmed, Osama AA; Hosny, Khaled M; Al-Sawahli, Majid M; Fahmy, Usama A

2015-01-01

The current study focuses on utilization of the natural biocompatible polymer zein to formulate simvastatin (SMV) nanoparticles coated with caseinate, to improve solubility and hence bioavailability, and in addition, to modify SMV-release characteristics. This formulation can be utilized for oral or possible depot parenteral applications. Fifteen formulations were prepared by liquid–liquid phase separation method, according to the Box–Behnken design, to optimize formulation variables. Sodium caseinate was used as an electrosteric stabilizer. The factors studied were: percentage of SMV in the SMV-zein mixture (X1), ethanol concentration (X2), and caseinate concentration (X3). The selected dependent variables were mean particle size (Y1), SMV encapsulation efficiency (Y2), and cumulative percentage of drug permeated after 1 hour (Y3). The diffusion of SMV from the prepared nanoparticles specified by the design was carried out using an automated Franz diffusion cell apparatus. The optimized SMV-zein formula was investigated for in vivo pharmacokinetic parameters compared with an oral SMV suspension. The optimized nanosized SMV-zein formula showed a 131 nm mean particle size and 89% encapsulation efficiency. In vitro permeation studies displayed delayed permeation characteristics, with about 42% and 85% of SMV cumulative amount released after 12 and 48 hours, respectively. Bioavailability estimation in rats revealed an augmentation in SMV bioavailability from the optimized SMV-zein formulation, by fourfold relative to SMV suspension. Formulation of caseinate-coated SMV-zein nanoparticles improves the pharmacokinetic profile and bioavailability of SMV. Accordingly, improved hypolipidemic activities for longer duration could be achieved. In addition, the reduced dosage rate of SMV-zein nanoparticles improves patient tolerability and compliance. PMID:25670883

Evaluation of Volatile Species in Green Monopropellant Project

NASA Technical Reports Server (NTRS)

Greene, Benjamin

2015-01-01

NASA is interested in green monopropellants to replace hydrazine in reaction control systems (RCSs). Some current NASA programs require reduced vapor pressure and low toxicity monopropellant (green) and superior performance (specific impulse and density) formulations. Earlier vapor phase studies of a candidate green monopropellant at the NASA White Sands Test Facility (WSTF) showed the presence of a volatile species that warranted further investigation. The purpose of this study was to further characterize the volatile species and to evaluate it. The evaluation was with respect to whether the volatile species was an impurity or how it is formed, and to use that information to examine whether its presence as an impurity can be eliminated during formulation. The evaluation also considered whether formation of the volatile impurity could be prevented while not compromising the propellant. To reduce variables associated with evaluation of the propellant formulation as a whole, a precursor to one of the individual components in the propellant formulation was subjected to a NASA Standard 6001B Flammability, Off-gassing, and Compatibility Requirements and Test Procedures "Determination of Off-gassed Products (Test 7)". Testing took place in the NASA WSTF Molecular Desorption and Analysis Laboratory. One gram of the precursor was placed in a flask within a specimen container. After thermal conditioning for 72 +/- 1 h at 50 +/- 3 deg C (122 +/- 5 deg F), the atmosphere inside the specimen container was analyzed for off-gassed compounds by cryotrap gas chromatography-mass spectrometry (GC-MS) and fixed sample loop GC-flame ionization detection (GC-FID). The specimen container used was glass to minimize potential catalytic surfaces. The identification of compounds was difficult due to the complexity of the vapor phase concentrations and overlapping chromatographic peaks and mass spectra. However, eleven compounds were specifically identified and five compounds or classes of compounds were reported as unidentified. Quantitation of most of the compounds, including unidentified compounds, was as methane. Quantitating compounds or classes of compounds that were detected but for which specific calibration is not established as methane is in accordance with the Test 7 standard protocol. The thermal decomposition temperature of the precursor was significantly higher than the test temperature. Based on thermal decomposition temperature and on an examination of the structure and chemistry of the identified volatile species, the presence of the volatile species appears to be chemically reasonable with respect to the propellant formulation and is at this time attributed to impurities. Further examination of the overall propellant formulation process (including the individual components' synthesis processes) and process quality control (including purity of reagents and possible decomposition reactions) is indicated.

Collaborative Workshops for Assessment and Creation of Multi-Objective Decision Support for Multiple Sectors

NASA Astrophysics Data System (ADS)

Kasprzyk, J. R.; Smith, R.; Raseman, W. J.; DeRousseau, M. A.; Dilling, L.; Ozekin, K.; Summers, R. S.; Balaji, R.; Livneh, B.; Rosario-Ortiz, F.; Sprain, L.; Srubar, W. V., III

2017-12-01

This presentation will report on three projects that used interactive workshops with stakeholders to develop problem formulations for Multi-Objective Evolutionary Algorithm (MOEA)-based decision support in diverse fields - water resources planning, water quality engineering under climate extremes, and sustainable materials design. When combined with a simulation model of a system, MOEAs use intelligent search techniques to provide new plans or designs. This approach is gaining increasing prominence in design and planning for environmental sustainability. To use this technique, a problem formulation - objectives and constraints (quantitative measures of performance) and decision variables (actions that can be modified to improve the system) - must be identified. Although critically important for MOEA effectiveness, the problem formulations are not always developed with stakeholders' interests in mind. To ameliorate this issue, project workshops were organized to improve the tool's relevance as well as collaboratively build problem formulations that can be used in applications. There were interesting differences among the projects, which altered the findings of each workshop. Attendees ranged from a group of water managers on the Front Range of Colorado, to water utility representatives from across the country, to a set of designers, academics, and trade groups. The extent to which the workshop participants were already familiar with simulation tools contributed to their willingness to accept the solutions that were generated using the tool. Moreover, in some instances, brainstorming new objectives to include within the MOEA expanded the scope of the problem formulation, relative to the initial conception of the researchers. Through describing results across a diversity of projects, the goal of this presentation is to report on how our approach may inform future decision support collaboration with a variety of stakeholders and sectors.

Connecting Atlantic temperature variability and biological cycling in two earth system models

NASA Astrophysics Data System (ADS)

Gnanadesikan, Anand; Dunne, John P.; Msadek, Rym

2014-05-01

Connections between the interdecadal variability in North Atlantic temperatures and biological cycling have been widely hypothesized. However, it is unclear whether such connections are due to small changes in basin-averaged temperatures indicated by the Atlantic Multidecadal Oscillation (AMO) Index, or whether both biological cycling and the AMO index are causally linked to changes in the Atlantic Meridional Overturning Circulation (AMOC). We examine interdecadal variability in the annual and month-by-month diatom biomass in two Earth System Models with the same formulations of atmospheric, land, sea ice and ocean biogeochemical dynamics but different formulations of ocean physics and thus different AMOC structures and variability. In the isopycnal-layered ESM2G, strong interdecadal changes in surface salinity associated with changes in AMOC produce spatially heterogeneous variability in convection, nutrient supply and thus diatom biomass. These changes also produce changes in ice cover, shortwave absorption and temperature and hence the AMO Index. Off West Greenland, these changes are consistent with observed changes in fisheries and support climate as a causal driver. In the level-coordinate ESM2M, nutrient supply is much higher and interdecadal changes in diatom biomass are much smaller in amplitude and not strongly linked to the AMO index.

Application of the Galerkin/least-squares formulation to the analysis of hypersonic flows. II - Flow past a double ellipse

NASA Technical Reports Server (NTRS)

Chalot, F.; Hughes, T. J. R.; Johan, Z.; Shakib, F.

1991-01-01

A finite element method for the compressible Navier-Stokes equations is introduced. The discretization is based on entropy variables. The methodology is developed within the framework of a Galerkin/least-squares formulation to which a discontinuity-capturing operator is added. Results for four test cases selected among those of the Workshop on Hypersonic Flows for Reentry Problems are presented.

Application of the Galerkin/least-squares formulation to the analysis of hypersonic flows. I - Flow over a two-dimensional ramp

NASA Technical Reports Server (NTRS)

Chalot, F.; Hughes, T. J. R.; Johan, Z.; Shakib, F.

1991-01-01

An FEM for the compressible Navier-Stokes equations is introduced. The discretization is based on entropy variables. The methodology is developed within the framework of a Galerkin/least-squares formulation to which a discontinuity-capturing operator is added. Results for three test cases selected among those of the Workshop on Hypersonic Flows for Reentry Problems are presented.

Development of performance matrix for generic product equivalence of acyclovir topical creams.

PubMed

Krishnaiah, Yellela S R; Xu, Xiaoming; Rahman, Ziyaur; Yang, Yang; Katragadda, Usha; Lionberger, Robert; Peters, John R; Uhl, Kathleen; Khan, Mansoor A

2014-11-20

The effect of process variability on physicochemical characteristics and in vitro performance of qualitatively (Q1) and quantitatively (Q2) equivalent generic acyclovir topical dermatological creams was investigated to develop a matrix of standards for determining their in vitro bioequivalence with reference listed drug (RLD) product (Zovirax®). A fractional factorial design of experiment (DOE) with triplicate center point was used to create 11 acyclovir cream formulations with manufacturing variables such as pH of aqueous phase, emulsification time, homogenization speed, and emulsification temperature. Three more formulations (F-12-F-14) with drug particle size representing RLD were also prepared where the pH of the final product was adjusted. The formulations were subjected to physicochemical characterization (drug particle size, spreadability, viscosity, pH, and drug concentration in aqueous phase) and in vitro drug release studies against RLD. The results demonstrated that DOE formulations were structurally and functionally (e.g., drug release) similar (Q3) to RLD. Moreover, in vitro drug permeation studies showed that extent of drug bioavailability/retention in human epidermis from F-12-F-14 were similar to RLD, although differed in rate of permeation. The results suggested generic acyclovir creams can be manufactured to obtain identical performance as that of RLD with Q1/Q2/Q3. Published by Elsevier B.V.

Fuzzy multiobjective models for optimal operation of a hydropower system

NASA Astrophysics Data System (ADS)

Teegavarapu, Ramesh S. V.; Ferreira, André R.; Simonovic, Slobodan P.

2013-06-01

Optimal operation models for a hydropower system using new fuzzy multiobjective mathematical programming models are developed and evaluated in this study. The models use (i) mixed integer nonlinear programming (MINLP) with binary variables and (ii) integrate a new turbine unit commitment formulation along with water quality constraints used for evaluation of reservoir downstream impairment. Reardon method used in solution of genetic algorithm optimization problems forms the basis for development of a new fuzzy multiobjective hydropower system optimization model with creation of Reardon type fuzzy membership functions. The models are applied to a real-life hydropower reservoir system in Brazil. Genetic Algorithms (GAs) are used to (i) solve the optimization formulations to avoid computational intractability and combinatorial problems associated with binary variables in unit commitment, (ii) efficiently address Reardon method formulations, and (iii) deal with local optimal solutions obtained from the use of traditional gradient-based solvers. Decision maker's preferences are incorporated within fuzzy mathematical programming formulations to obtain compromise operating rules for a multiobjective reservoir operation problem dominated by conflicting goals of energy production, water quality and conservation releases. Results provide insight into compromise operation rules obtained using the new Reardon fuzzy multiobjective optimization framework and confirm its applicability to a variety of multiobjective water resources problems.

Liquid-Liquid Phase Separation in a Dual Variable Domain Immunoglobulin Protein Solution: Effect of Formulation Factors and Protein-Protein Interactions.

PubMed

Raut, Ashlesha S; Kalonia, Devendra S

2015-09-08

Dual variable domain immunoglobulin proteins (DVD-Ig proteins) are large molecules (MW ∼ 200 kDa) with increased asymmetry because of their extended Y-like shape, which results in increased formulation challenges. Liquid-liquid phase separation (LLPS) of protein solutions into protein-rich and protein-poor phases reduces solution stability at intermediate concentrations and lower temperatures, and is a serious concern in formulation development as therapeutic proteins are generally stored at refrigerated conditions. In the current work, LLPS was studied for a DVD-Ig protein molecule as a function of solution conditions by measuring solution opalescence. LLPS of the protein was confirmed by equilibrium studies and by visually observing under microscope. The protein does not undergo any structural change after phase separation. Protein-protein interactions were measured by light scattering (kD) and Tcloud (temperature that marks the onset of phase separation). There is a good agreement between kD measured in dilute solution with Tcloud measured in the critical concentration range. Results indicate that the increased complexity of the molecule (with respect to size, shape, and charge distribution on the molecule) increases contribution of specific and nonspecific interactions in solution, which are affected by formulation factors, resulting in LLPS for DVD-Ig protein.

Application of Box-Behnken design for preparation of levofloxacin-loaded stearic acid solid lipid nanoparticles for ocular delivery: Optimization, in vitro release, ocular tolerance, and antibacterial activity.

PubMed

Baig, Mirza Salman; Ahad, Abdul; Aslam, Mohammed; Imam, Syed Sarim; Aqil, Mohd; Ali, Asgar

2016-04-01

The aim of the present study was to develop and optimize levofloxacin loaded solid lipid nanoparticles for the treatment of conjunctivitis. Box-Behnken experimental design was applied for optimization of solid lipid nanoparticles. The independent variables were stearic acid as lipid (X1), Tween 80 as surfactant (X2) and sodium deoxycholate as co-surfactant (X3) while particle size (Y1) and entrapment efficiency (Y2) were the dependent variables. Further in vitro release and antibacterial activity in vitro were also performed. The optimized formulation of levofloxacin provides particle size of 237.82 nm and showed 78.71% entrapment efficiency and achieved flux 0.2,493 μg/cm(2)/h across excised goat cornea. In vitro release study showed prolonged drug release from the optimized formulation following Korsmeyer-Peppas model. Antimicrobial study revealed that the developed formulation possesses antibacterial activity against Staphylococcus aureus, and Escherichia coli equivalent to marketed eye drops. HET-CAM test demonstrated that optimized formulation was found to be non-irritant and safe for topical ophthalmic use. Our results concluded that solid lipid nanoparticles are an efficient carrier for ocular delivery of levofloxacin and other drugs. Copyright © 2015 Elsevier B.V. All rights reserved.

Development of in vitro-in vivo correlation for extended-release niacin after administration of hypromellose-based matrix formulations to healthy volunteers.

PubMed

Kesisoglou, Filippos; Rossenu, Stefaan; Farrell, Colm; Van Den Heuvel, Michiel; Prohn, Marita; Fitzpatrick, Shaun; De Kam, Pieter-Jan; Vargo, Ryan

2014-11-01

Development of in vitro-in vivo correlations (IVIVCs) for extended-release (ER) products is commonly pursued during pharmaceutical development to increase product understanding, set release specifications, and support biowaivers. This manuscript details the development of Level C and Level A IVIVCs for ER formulations of niacin, a highly variable and extensively metabolized compound. Three ER formulations were screened in a cross-over study against immediate-release niacin. A Multiple Level C IVIVC was established for both niacin and its primary metabolite nicotinuric acid (NUA) as well as total niacin metabolites urinary excretion. For NUA, but not for niacin, Level A IVIVC models with acceptable prediction errors were achievable via a modified IVIVC rather than a traditional deconvolution/convolution approach. Hence, this is in contradiction with current regulatory guidelines that suggest that when a Multiple Level C IVIVC is established, Level A models should also be readily achievable. We demonstrate that for a highly variable, highly metabolized compound such as niacin, development of a Level A IVIVC model fully validated according to agency guidelines may be challenging. However, Multiple Level C models are achievable and could be used to guide release specifications and formulation/manufacturing changes. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Development of Probabilistic Rigid Pavement Design Methodologies for Military Airfields.

DTIC Science & Technology

1983-12-01

4A161102AT22, Task AO, Work Unit 009, "Methodology for Considering Material Variability in Pavement Design." OCE Project Monitor was Mr. S. S. Gillespie. The...PREFACE. .. ............................. VOLUME 1: STATE OF THE ART VARIABILITY OF AIRFIELD PAVEMENT MATERIALS VOLUME 11: MATHEMATICAL FORMULATION OF...VOLUME IV: PROBABILISTIC ANALYSIS OF RIGID AIRFIELD DESIGN BY ELASTIC LAYERED THEORY VOLUME I STATE OF THE ART VARIABILITY OF AIRFIELD PAVEMENT MATERIALS

Development of transethosomes formulation for dermal fisetin delivery: Box-Behnken design, optimization, in vitro skin penetration, vesicles-skin interaction and dermatokinetic studies.

PubMed

Moolakkadath, Thasleem; Aqil, Mohd; Ahad, Abdul; Imam, Syed Sarim; Iqbal, Babar; Sultana, Yasmin; Mujeeb, Mohd; Iqbal, Zeenat

2018-05-07

The present study was conducted for the optimization of transethosomes formulation for dermal fisetin delivery. The optimization of the formulation was carried out using "Box-Behnken design". The independent variables were Lipoid S 100, ethanol and sodium cholate. The prepared formulations were characterized for vesicle size, entrapment efficiency and in vitro skin penetration study. The vesicles-skin interaction, confocal laser scanning microscopy and dermatokinetic studies were performed with optimized formulation. Results of the present study demonstrated that the optimized formulation presented vesicle size of 74.21 ± 2.65 nm, zeta potential of -11.0 mV, entrapment efficiency of 68.31 ± 1.48% and flux of 4.13 ± 0.17 µg/cm 2 /h. The TEM image of optimized formulation exhibited sealed and spherical shape vesicles. Results of thermoanalytical techniques demonstrated that the prepared transethosomes vesicles formulation had fluidized the rigid membrane of rat's skin for smoother penetration of fisetin transethosomes. The confocal study results presented well distribution and penetration of Rhodamine B loaded transethosomes vesicles formulation up to deeper layers of the rat's skin as compared to the Rhodamine B-hydro alcoholic solution. Present study data revealed that the developed transethosomes vesicles formulation was found to be a potentially useful drug carrier for fisetin dermal delivery.

Exploratory Long-Range Models to Estimate Summer Climate Variability over Southern Africa.

NASA Astrophysics Data System (ADS)

Jury, Mark R.; Mulenga, Henry M.; Mason, Simon J.

1999-07-01

Teleconnection predictors are explored using multivariate regression models in an effort to estimate southern African summer rainfall and climate impacts one season in advance. The preliminary statistical formulations include many variables influenced by the El Niño-Southern Oscillation (ENSO) such as tropical sea surface temperatures (SST) in the Indian and Atlantic Oceans. Atmospheric circulation responses to ENSO include the alternation of tropical zonal winds over Africa and changes in convective activity within oceanic monsoon troughs. Numerous hemispheric-scale datasets are employed to extract predictors and include global indexes (Southern Oscillation index and quasi-biennial oscillation), SST principal component scores for the global oceans, indexes of tropical convection (outgoing longwave radiation), air pressure, and surface and upper winds over the Indian and Atlantic Oceans. Climatic targets include subseasonal, area-averaged rainfall over South Africa and the Zambezi river basin, and South Africa's annual maize yield. Predictors and targets overlap in the years 1971-93, the defined training period. Each target time series is fitted by an optimum group of predictors from the preceding spring, in a linear multivariate formulation. To limit artificial skill, predictors are restricted to three, providing 17 degrees of freedom. Models with colinear predictors are screened out, and persistence of the target time series is considered. The late summer rainfall models achieve a mean r2 fit of 72%, contributed largely through ENSO modulation. Early summer rainfall cross validation correlations are lower (61%). A conceptual understanding of the climate dynamics and ocean-atmosphere coupling processes inherent in the exploratory models is outlined.Seasonal outlooks based on the exploratory models could help mitigate the impacts of southern Africa's fluctuating climate. It is believed that an advance warning of drought risk and seasonal rainfall prospects will improve the economic growth potential of southern Africa and provide additional security for food and water supplies.

Students’ Mathematical Literacy in Solving PISA Problems Based on Keirsey Personality Theory

NASA Astrophysics Data System (ADS)

Masriyah; Firmansyah, M. H.

2018-01-01

This research is descriptive-qualitative research. The purpose is to describe students’ mathematical literacy in solving PISA on space and shape content based on Keirsey personality theory. The subjects are four junior high school students grade eight with guardian, artisan, rational or idealist personality. Data collecting methods used test and interview. Data of Keirsey Personality test, PISA test, and interview were analysed. Profile of mathematical literacy of each subject are described as follows. In formulating, guardian subject identified mathematical aspects are formula of rectangle area and sides length; significant variables are terms/conditions in problem and formula of ever encountered question; translated into mathematical language those are measurement and arithmetic operations. In employing, he devised and implemented strategies using ease of calculation on area-subtraction principle; declared truth of result but the reason was less correct; didn’t use and switch between different representations. In interpreting, he declared result as area of house floor; declared reasonableness according measurement estimation. In formulating, artisan subject identified mathematical aspects are plane and sides length; significant variables are solution procedure on both of daily problem and ever encountered question; translated into mathematical language those are measurement, variables, and arithmetic operations as well as symbol representation. In employing, he devised and implemented strategies using two design comparison; declared truth of result without reason; used symbol representation only. In interpreting, he expressed result as floor area of house; declared reasonableness according measurement estimation. In formulating, rational subject identified mathematical aspects are scale and sides length; significant variables are solution strategy on ever encountered question; translated into mathematical language those are measurement, variable, arithmetic operation as well as symbol and graphic representation. In employing, he devised and implemented strategies using additional plane forming on area-subtraction principle; declared truth of result according calculation process; used and switched between symbol and graphic representation. In interpreting, he declared result as house area within terrace and wall; declared reasonableness according measurement estimation. In formulating, idealist subject identified mathematical aspects are sides length; significant variables are terms/condition in problem; translated into mathematical language those are measurement, variables, arithmetic operations as well as symbol and graphic representation. In employing, he devised and implemented strategies using trial and error and two design in process of finding solutions; declared truth of result according the use of two design of solution; used and switched between symbol and graphic representation. In interpreting, he declared result as floor area of house; declared reasonableness according measurement estimation.

Protein labeling reactions in electrochemical microchannel flow: Numerical simulation and uncertainty propagation

NASA Astrophysics Data System (ADS)

Debusschere, Bert J.; Najm, Habib N.; Matta, Alain; Knio, Omar M.; Ghanem, Roger G.; Le Maître, Olivier P.

2003-08-01

This paper presents a model for two-dimensional electrochemical microchannel flow including the propagation of uncertainty from model parameters to the simulation results. For a detailed representation of electroosmotic and pressure-driven microchannel flow, the model considers the coupled momentum, species transport, and electrostatic field equations, including variable zeta potential. The chemistry model accounts for pH-dependent protein labeling reactions as well as detailed buffer electrochemistry in a mixed finite-rate/equilibrium formulation. Uncertainty from the model parameters and boundary conditions is propagated to the model predictions using a pseudo-spectral stochastic formulation with polynomial chaos (PC) representations for parameters and field quantities. Using a Galerkin approach, the governing equations are reformulated into equations for the coefficients in the PC expansion. The implementation of the physical model with the stochastic uncertainty propagation is applied to protein-labeling in a homogeneous buffer, as well as in two-dimensional electrochemical microchannel flow. The results for the two-dimensional channel show strong distortion of sample profiles due to ion movement and consequent buffer disturbances. The uncertainty in these results is dominated by the uncertainty in the applied voltage across the channel.

PKPD model of interleukin-21 effects on thermoregulation in monkeys--application and evaluation of stochastic differential equations.

PubMed

Overgaard, Rune Viig; Holford, Nick; Rytved, Klaus A; Madsen, Henrik

2007-02-01

To describe the pharmacodynamic effects of recombinant human interleukin-21 (IL-21) on core body temperature in cynomolgus monkeys using basic mechanisms of heat regulation. A major effort was devoted to compare the use of ordinary differential equations (ODEs) with stochastic differential equations (SDEs) in pharmacokinetic pharmacodynamic (PKPD) modelling. A temperature model was formulated including circadian rhythm, metabolism, heat loss, and a thermoregulatory set-point. This model was formulated as a mixed-effects model based on SDEs using NONMEM. The effects of IL-21 were on the set-point and the circadian rhythm of metabolism. The model was able to describe a complex set of IL-21 induced phenomena, including 1) disappearance of the circadian rhythm, 2) no effect after first dose, and 3) high variability after second dose. SDEs provided a more realistic description with improved simulation properties, and further changed the model into one that could not be falsified by the autocorrelation function. The IL-21 induced effects on thermoregulation in cynomolgus monkeys are explained by a biologically plausible model. The quality of the model was improved by the use of SDEs.

Microencapsulation of superoxide dismutase into poly(epsilon-caprolactone) microparticles by reverse micelle solvent evaporation.

PubMed

Youan, Bi-Botti Célestin

2003-01-01

The aim of this work was to encapsulate superoxide dismutase (SOD) in poly(epsilon-caprolactone) (PCL) microparticles by reverse micelle solvent evaporation. The concentration of PCL, the hydrophile-lipophile balance (HLB), and concentration of the sucrose ester used as surfactant in the organic phase were investigated as formulation variables. Relatively higher encapsulation efficiency (approximately 48%) and retained enzymatic activity (>90%) were obtained with microparticle formulation made from the 20% (w/v) PCL and 0.05% (w/v) sucrose ester of HLB = 6. This formulation allowed the in vitro release of SOD for at least 72 hr. These results showed that reverse micelle solvent evaporation can be used to efficiently encapsulate SOD in PCL microparticles. Such formulations may improve the bioavailability of SOD.

A computational analysis of lower bounds for the economic lot sizing problem in remanufacturing with separate setups

NASA Astrophysics Data System (ADS)

Aishah Syed Ali, Sharifah

2017-09-01

This paper considers economic lot sizing problem in remanufacturing with separate setup (ELSRs), where remanufactured and new products are produced on dedicated production lines. Since this problem is NP-hard in general, which leads to computationally inefficient and low-quality of solutions, we present (a) a multicommodity formulation and (b) a strengthened formulation based on a priori addition of valid inequalities in the space of original variables, which are then compared with the Wagner-Whitin based formulation available in the literature. Computational experiments on a large number of test data sets are performed to evaluate the different approaches. The numerical results show that our strengthened formulation outperforms all the other tested approaches in terms of linear relaxation bounds. Finally, we conclude with future research directions.

A programing system for research and applications in structural optimization

NASA Technical Reports Server (NTRS)

Sobieszczanski-Sobieski, J.; Rogers, J. L., Jr.

1981-01-01

The paper describes a computer programming system designed to be used for methodology research as well as applications in structural optimization. The flexibility necessary for such diverse utilizations is achieved by combining, in a modular manner, a state-of-the-art optimization program, a production level structural analysis program, and user supplied and problem dependent interface programs. Standard utility capabilities existing in modern computer operating systems are used to integrate these programs. This approach results in flexibility of the optimization procedure organization and versatility in the formulation of contraints and design variables. Features shown in numerical examples include: (1) variability of structural layout and overall shape geometry, (2) static strength and stiffness constraints, (3) local buckling failure, and (4) vibration constraints. The paper concludes with a review of the further development trends of this programing system.

Bayesian Analysis of Structural Equation Models with Nonlinear Covariates and Latent Variables

ERIC Educational Resources Information Center

Song, Xin-Yuan; Lee, Sik-Yum

2006-01-01

In this article, we formulate a nonlinear structural equation model (SEM) that can accommodate covariates in the measurement equation and nonlinear terms of covariates and exogenous latent variables in the structural equation. The covariates can come from continuous or discrete distributions. A Bayesian approach is developed to analyze the…

Robustness-Based Design Optimization Under Data Uncertainty

NASA Technical Reports Server (NTRS)

Zaman, Kais; McDonald, Mark; Mahadevan, Sankaran; Green, Lawrence

2010-01-01

This paper proposes formulations and algorithms for design optimization under both aleatory (i.e., natural or physical variability) and epistemic uncertainty (i.e., imprecise probabilistic information), from the perspective of system robustness. The proposed formulations deal with epistemic uncertainty arising from both sparse and interval data without any assumption about the probability distributions of the random variables. A decoupled approach is proposed in this paper to un-nest the robustness-based design from the analysis of non-design epistemic variables to achieve computational efficiency. The proposed methods are illustrated for the upper stage design problem of a two-stage-to-orbit (TSTO) vehicle, where the information on the random design inputs are only available as sparse point and/or interval data. As collecting more data reduces uncertainty but increases cost, the effect of sample size on the optimality and robustness of the solution is also studied. A method is developed to determine the optimal sample size for sparse point data that leads to the solutions of the design problem that are least sensitive to variations in the input random variables.

Linear and nonlinear dynamic analysis by boundary element method. Ph.D. Thesis, 1986 Final Report

NASA Technical Reports Server (NTRS)

Ahmad, Shahid

1991-01-01

An advanced implementation of the direct boundary element method (BEM) applicable to free-vibration, periodic (steady-state) vibration and linear and nonlinear transient dynamic problems involving two and three-dimensional isotropic solids of arbitrary shape is presented. Interior, exterior, and half-space problems can all be solved by the present formulation. For the free-vibration analysis, a new real variable BEM formulation is presented which solves the free-vibration problem in the form of algebraic equations (formed from the static kernels) and needs only surface discretization. In the area of time-domain transient analysis, the BEM is well suited because it gives an implicit formulation. Although the integral formulations are elegant, because of the complexity of the formulation it has never been implemented in exact form. In the present work, linear and nonlinear time domain transient analysis for three-dimensional solids has been implemented in a general and complete manner. The formulation and implementation of the nonlinear, transient, dynamic analysis presented here is the first ever in the field of boundary element analysis. Almost all the existing formulation of BEM in dynamics use the constant variation of the variables in space and time which is very unrealistic for engineering problems and, in some cases, it leads to unacceptably inaccurate results. In the present work, linear and quadratic isoparametric boundary elements are used for discretization of geometry and functional variations in space. In addition, higher order variations in time are used. These methods of analysis are applicable to piecewise-homogeneous materials, such that not only problems of the layered media and the soil-structure interaction can be analyzed but also a large problem can be solved by the usual sub-structuring technique. The analyses have been incorporated in a versatile, general-purpose computer program. Some numerical problems are solved and, through comparisons with available analytical and numerical results, the stability and high accuracy of these dynamic analysis techniques are established.

Physical and Chemical Microstructural Damage in Pressed CL-20 explosives

NASA Astrophysics Data System (ADS)

Demol, Gauthier; Sandusky, Harold W.

1999-06-01

Based upon its molecular composition, its structure, and its heat of formation, it was expected that CL-20 (hexanitrohexaazaisowurtzitane) would be more energetic and more sensitive than RDX and HMX. Reports of batch-to-batch variations in the sensitivity of neat CL-20 have led to its sensitivity being ranked in the range between the sensitivity of RDX and that of PETN. The ultimate utility of CL-20 as an ingredient in explosive and propellant formulations will depend upon the ability to understand the factors that are responsible for this batch-to-batch variability, and to control the sensitivity in formulations within acceptable limits. This work is a characterization of CL-20 at various stages in its life cycle. The evolution of damage from the initial neat crystals of CL-20 to the ready-to-use pressed pellets will be described. This characterization includes physical documentation using light microscopy and Scanning Electron Microscopy. Spatially resolved chemical analysis is also performed using Fourier-Transform Infrared Spectroscopy.

Space-time variation of respiratory cancers in South Carolina: a flexible multivariate mixture modeling approach to risk estimation.

PubMed

Carroll, Rachel; Lawson, Andrew B; Kirby, Russell S; Faes, Christel; Aregay, Mehreteab; Watjou, Kevin

2017-01-01

Many types of cancer have an underlying spatiotemporal distribution. Spatiotemporal mixture modeling can offer a flexible approach to risk estimation via the inclusion of latent variables. In this article, we examine the application and benefits of using four different spatiotemporal mixture modeling methods in the modeling of cancer of the lung and bronchus as well as "other" respiratory cancer incidences in the state of South Carolina. Of the methods tested, no single method outperforms the other methods; which method is best depends on the cancer under consideration. The lung and bronchus cancer incidence outcome is best described by the univariate modeling formulation, whereas the "other" respiratory cancer incidence outcome is best described by the multivariate modeling formulation. Spatiotemporal multivariate mixture methods can aid in the modeling of cancers with small and sparse incidences when including information from a related, more common type of cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

[Pharmacology of the antifungals used in the treatment of aspergillosis].

PubMed

Azanza, José Ramón; Sádaba, Belén; Gómez-Guíu, Almudena

2014-01-01

The treatment of invasive aspergillosis requires the use of drugs that characteristically have complex pharmacokinetic properties, the knowledge of which is essential to achieve maximum efficacy with minimal risk to the patient. The lipid-based amphotericin B formulations vary significantly in their pharmacokinetic behaviour, with very high plasma concentrations of the liposomal form, probably related to the presence of cholesterol in their structure. Azoles have a variable absorption profile, particularly in the case of itraconazole and posaconazole, with the latter very dependent on multiple factors. This may also lead to variations in voriconazole, which requires considering the possibility of monitoring plasma concentrations. The aim of this article is to review some of the most relevant aspects of the pharmacology of the antifungals used in the prophylaxis and treatment of the Aspergillus infection. For this reason, it includes the most relevant features of some of the azoles normally prescribed in this infection (itraconazole, posaconazole and voriconazole) and the amphotericin B formulations. Copyright © 2014. Published by Elsevier Espana.

Docetaxel-loaded thermosensitive liquid suppository: optimization of rheological properties.

PubMed

Yeo, Woo Hyun; Ramasamy, Thiruganesh; Kim, Dong-Wuk; Cho, Hyuk Jun; Kim, Yong-Il; Cho, Kwan Hyung; Yong, Chul Soon; Kim, Jong Oh; Choi, Han-Gon

2013-12-01

The main purpose of this work was to optimize the rheological properties of docetaxel (DCT)-loaded thermosensitive liquid suppositories for rectal administration. DCT-loaded liquid suppositories were prepared by a cold method and characterized in terms of physicochemical and viscoelastic properties. Major formulation parameters including poloxamer (P407) and Tween 80 were optimized to adjust the thermogelling and mucoadhesive properties for rectal administration. Notably, the gel strength and mucoadhesive force significantly increased with the increase in these variables. Furthermore, DCT incorporation did not alter the viscoelastic behavior, and the mean particle size of nanomicelles in it was approximately 16 nm with a distinct spherical shape. The formulation existed as liquid at room temperature and transformed into gel at physiological temperature through the reverse gelation phenomenon. Thus, DCT-loaded thermosensitive liquid suppositories [DCT/P407/P188/Tween 80 (0.25/11/15/10 %)] with optimal gel properties were easy to prepare and administer rectally, and might enable the gel to stay in the rectum without getting out from rectum.

A new axi-symmetric element for thin walled structures

NASA Astrophysics Data System (ADS)

Cardoso, Rui P. R.; Yoon, Jeong Whan; Dick, Robert E.

2010-03-01

A new axi-symmetric finite element for thin walled structures is presented in this work. It uses the solid-shell element’s concept with only a single element and multiple integration points along the thickness direction. The cross-section of the element is composed of four nodes with two degrees of freedom each. The proposed formulation overcomes many locking pathologies including transverse shear locking, Poisson’s locking and volumetric locking. For transverse shear locking, the formulation uses the selective reduced integration technique, for Poisson’s locking it uses the enhanced assumed strain (EAS) method with only one enhancing variable. The B-bar approach is used to eliminate the isochoric deformations in the hourglass field while the EAS method is used to alleviate the volumetric locking in the constant part of the deformation tensor. Several examples are shown to demonstrate the performance and accuracy of the proposed element with special focus on the numerical simulations for the beverage can industry.

The influence of polymeric excipients on the process of pharmaceutical availability of therapeutic agents from a model drug form. Part I. In formulations with controlled disintegration and release time.

PubMed

Nachajski, Michal Jakub; Zgoda, Marian Mikołaj

2010-01-01

Pre-formulation research was conducted on the application of Ex. Echinaceae aq. siccum in the production of a quickly disintegrating suspension tablet, a lozenge with kariostatic sugar alcohols (mannitol, sorbitol), and, above all, a solid drug form with controlled release of therapeutic agents included in the extract. Morphological parameters of tablets obtained in the course of experiment were estimated and the profiles of the release (diffusion) ofhydrophilic therapeutic agents into model receptor fluids with varying values of osmolarity (0.1 mol HCl approximately 200 mOsm/l, hypotonic hydrating fluid approximately 143 mOsm/l, and compensatory paediatric fluid approximately 272 mOsm/l) were examined. The study focused on the technological problem of determining the effect of hydrogel Carbopol structure on the ordering of diffusion ofhydrophilic therapeutic agents from a model drug form (a tablet) into model fluids with variable osmolarity.

An Optimization-Based Approach to Determine Requirements and Aircraft Design under Multi-domain Uncertainties

NASA Astrophysics Data System (ADS)

Govindaraju, Parithi

Determining the optimal requirements for and design variable values of new systems, which operate along with existing systems to provide a set of overarching capabilities, as a single task is challenging due to the highly interconnected effects that setting requirements on a new system's design can have on how an operator uses this newly designed system. This task of determining the requirements and the design variable values becomes even more difficult because of the presence of uncertainties in the new system design and in the operational environment. This research proposed and investigated aspects of a framework that generates optimum design requirements of new, yet-to-be-designed systems that, when operating alongside other systems, will optimize fleet-level objectives while considering the effects of various uncertainties. Specifically, this research effort addresses the issues of uncertainty in the design of the new system through reliability-based design optimization methods, and uncertainty in the operations of the fleet through descriptive sampling methods and robust optimization formulations. In this context, fleet-level performance metrics result from using the new system alongside other systems to accomplish an overarching objective or mission. This approach treats the design requirements of a new system as decision variables in an optimization problem formulation that a user in the position of making an acquisition decision could solve. This solution would indicate the best new system requirements-and an associated description of the best possible design variable variables for that new system-to optimize the fleet level performance metric(s). Using a problem motivated by recorded operations of the United States Air Force Air Mobility Command for illustration, the approach is demonstrated first for a simplified problem that only considers demand uncertainties in the service network and the proposed methodology is used to identify the optimal design requirements and optimal aircraft sizing variables of new, yet-to-be-introduced aircraft. With this new aircraft serving alongside other existing aircraft, the fleet of aircraft satisfy the desired demand for cargo transportation, while maximizing fleet productivity and minimizing fuel consumption via a multi-objective problem formulation. The approach is then extended to handle uncertainties in both the design of the new system and in the operations of the fleet. The propagation of uncertainties associated with the conceptual design of the new aircraft to the uncertainties associated with the subsequent operations of the new and existing aircraft in the fleet presents some unique challenges. A computationally tractable hybrid robust counterpart formulation efficiently handles the confluence of the two types of domain-specific uncertainties. This hybrid formulation is tested on a larger route network problem to demonstrate the scalability of the approach. Following the presentation of the results obtained, a summary discussion indicates how decision-makers might use these results to set requirements for new aircraft that meet operational needs while balancing the environmental impact of the fleet with fleet-level performance. Comparing the solutions from the uncertainty-based and deterministic formulations via a posteriori analysis demonstrates the efficacy of the robust and reliability-based optimization formulations in addressing the different domain-specific uncertainties. Results suggest that the aircraft design requirements and design description determined through the hybrid robust counterpart formulation approach differ from solutions obtained from the simplistic deterministic approach, and leads to greater fleet-level fuel savings, when subjected to real-world uncertain scenarios (more robust to uncertainty). The research, though applied to a specific air cargo application, is technically agnostic in nature and can be applied to other facets of policy and acquisition management, to explore capability trade spaces for different vehicle systems, mitigate risks, define policy and potentially generate better returns on investment. Other domains relevant to policy and acquisition decisions could utilize the problem formulation and solution approach proposed in this dissertation provided that the problem can be split into a non-linear programming problem to describe the new system sizing and the fleet operations problem can be posed as a linear/integer programming problem.

In vitro/in vivo characterization of nanoemulsion formulation of metronidazole with improved skin targeting and anti-rosacea properties.

PubMed

Yu, Meng; Ma, Huixian; Lei, Mingzhu; Li, Nan; Tan, Fengping

2014-09-01

Topical skin treatment was limited due to the lack of suitable delivery system with significant cutaneous localization and systemic safety. The aim of this study was to develop and optimize a nanoemulsion (NE) to enhance targeting localization of metronidazole (MTZ) in skin layers. In vitro studies were used to optimize NE formulations, and a series of experiments were carried in vitro and in vivo to validate the therapeutic efficacy of MTZ-loaded optimal NE. NE type selection and D-optimal design study were applied to optimize NE formulation with maximum skin retention and minimum skin penetration. Three formulation variables: Oil X1 (Labrafil), Smix X2 (a mixture of Cremophor EL/Tetraethylene glycol, 2:1 w/w) and water X3 were included in D-design. The system was assessed for skin retention Y1, cumulative MTZ amount after 24 h Y2 and droplet size Y3. Following optimization, the values of formulation components (X1, X2 and X3) were 4.13%, 16.42% and 79.45%, respectively. The optimized NE was assessed for viscosity, droplet size, morphological study and in vitro permeation in pig skin. Distributions of MTZ were validated by confocal laser scanning microscopy (CLSM). Active agent of NE transferred into deeper skin and localized in epidermal/dermal layers after 24 h, which showed significant advantages of the optimal NE over Gel. The skin targeting localization and minimal systemic escape of optimal NE was further proved by in vivo study on rat skin. Current in vitro-in vivo correlation (IVIVC) enabled the prediction of pharmacokinetic profile of MTZ from in vitro permeation results. Further, the in vivo anti-rosacea efficacy of optimal formulation was investigated by pharmacodynamics study on mice ear. Copyright © 2014 Elsevier B.V. All rights reserved.

A New and General Formulation of the Parametric HFGMC Micromechanical Method for Three-Dimensional Multi-Phase Composites

NASA Technical Reports Server (NTRS)

Haj-Ali, Rami; Aboudi, Jacob

2012-01-01

The recent two-dimensional (2-D) parametric formulation of the high fidelity generalized method of cells (HFGMC) reported by the authors is generalized for the micromechanical analysis of three-dimensional (3-D) multiphase composites with periodic microstructure. Arbitrary hexahedral subcell geometry is developed to discretize a triply periodic repeating unit-cell (RUC). Linear parametric-geometric mapping is employed to transform the arbitrary hexahedral subcell shapes from the physical space to an auxiliary orthogonal shape, where a complete quadratic displacement expansion is performed. Previously in the 2-D case, additional three equations are needed in the form of average moments of equilibrium as a result of the inclusion of the bilinear terms. However, the present 3-D parametric HFGMC formulation eliminates the need for such additional equations. This is achieved by expressing the coefficients of the full quadratic polynomial expansion of the subcell in terms of the side or face average-displacement vectors. The 2-D parametric and orthogonal HFGMC are special cases of the present 3-D formulation. The continuity of displacements and tractions, as well as the equilibrium equations, are imposed in the average (integral) sense as in the original HFGMC formulation. Each of the six sides (faces) of a subcell has an independent average displacement micro-variable vector which forms an energy-conjugate pair with the transformed average-traction vector. This allows generating symmetric stiffness matrices along with internal resisting vectors for the subcells which enhances the computational efficiency. The established new parametric 3-D HFGMC equations are formulated and solution implementations are addressed. Several applications for triply periodic 3-D composites are presented to demonstrate the general capability and varsity of the present parametric HFGMC method for refined micromechanical analysis by generating the spatial distributions of local stress fields. These applications include triply periodic composites with inclusions in the form of a cavity, spherical inclusion, ellipsoidal inclusion, discontinuous aligned short fiber. A 3-D repeating unit-cell for foam material composite is simulated.

Pharmacokinetic and pharmacodynamic comparison of hydrofluoroalkane and chlorofluorocarbon formulations of budesonide

PubMed Central

Clearie, Karine L; Williamson, Peter A; Meldrum, Karen; Gillen, Michael; Carlsson, Lars-Goran; Carlholm, Marie; Ekelund, Jan; Lipworth, Brian J

2011-01-01

AIMS A hydrofluoroalkane formulation of budesonide pressurized metered-dose inhaler has been developed to replace the existing chlorofluorocarbon one. The aim of this study was to evaluate the pharmacokinetic and pharmacodynamic characteristics of both formulations. METHODS Systemic bioavailability and bioactivity of both hydrofluoroalkane and chlorofluorocarbon pressurized metered-dose inhaler formulations at 800 µg twice daily was determined during a randomized crossover systemic pharmacokinetic/pharmacodynamic study at steady state in healthy volunteers. Measurements included the following: plasma cortisol AUC24h[area under the concentration-time curve (0–24 h)], budesonide AUC0–12h and Cmax. Clinical efficacy was determined during a randomized crossover pharmacodynamic study in asthmatic patients receiving 200 µg followed by 800 µg budesonide via chlorofluorocarbon or hydrofluoroalkane pressurized metered-dose inhaler each for 4 weeks. Methacholine PC20 (primary outcome), exhaled nitric oxide, spirometry, peak expiratory flow and symptoms were evaluated. RESULTS In the pharmacokinetic study, there were no differences in cortisol, AUC0–12h[area under the concentration-time curve (0–12 h)], Tmax (time to maximum concentration) or Cmax (peak serum concentration) between the hydrofluoroalkane and chlorofluorocarbon pressurized metered-dose inhaler. The ratio of budesonide hydrofluoroalkane vs. chlorofluorocarbon pressurized metered-dose inhaler for cortisol AUC24h was 1.02 (95% confidence interval 0.93–1.11) and budesonide AUC0–12h was 1.03 (90% confidence interval 0.9–1.18). In the asthma pharmacodynamic study, there was a significant dose response (P < 0.0001) for methacholine PC20 (provocative concentration of methacholine needed to produce a 20% fall in FEV1) with a relative potency ratio of 1.10 (95% confidence interval 0.49–2.66), and no difference at either dose. No significant differences between formulations were seen with the secondary outcome variables. CONCLUSIONS Hydrofluoroalkane and chlorofluorocarbon formulations of budesonide were therapeutically equivalent in terms of relative lung bioavailability, airway efficacy and systemic effects. PMID:21395643

Nanomedicines for HIV therapy.

PubMed

Siccardi, Marco; Martin, Philip; McDonald, Tom O; Liptrott, Neill J; Giardiello, Marco; Rannard, Steve; Owen, Andrew

2013-02-01

Heterogeneity in response to HIV treatments has been attributed to several causes including variability in pharmacokinetic exposure. Nanomedicine applications have a variety of advantages compared with traditional formulations, such as the potential to increase bioavailability and specifically target the site of action. Our group is focusing on the development of nanoformulations using a closed-loop design process in which nanoparticle optimization (disposition, activity and safety) is a continuous process based on experimental pharmacological data from in vitro and in vivo models. Solid drug nanoparticles, polymer-based drug-delivery carriers as well as nanoemulsions are nanomedicine options with potential application to improve antiretroviral deployment.

The Seasat surface truth experiments

NASA Technical Reports Server (NTRS)

Shemdin, O. H.

1976-01-01

A surface truth program for Seasat A is formulated in two phases: pre- and post-launch. The pre-launch phase (which includes the Marineland experiments, the JONSWAP-75 experiment, the West Coast experiment, and the altimeter experiment) is designed to provide data from aircraft over instrumented ocean sites during desirable geophysical events. The objective is to gather sufficient data for the development of algorithms which transfer space data into geophysical variables useful for applications. In the post-launch phase, the surface truth program is designed to verify and improve the algorithms developed in the pre-launch phase and also to evaluate the performance of spaceborne sensors.

Design fabrication and test of graphite/polyimide composite joints and attachments for advanced aerospace vehicles

NASA Technical Reports Server (NTRS)

1979-01-01

Graphite/polyimide (Gr/PI) bolted and bonded joints were investigated. Possible failure modes and the design loads for the four generic joint types are discussed. Preliminary sizing of a type 1 joint, bonded and bolted configuration is described, including assumptions regarding material properties and sizing methodology. A general purpose finite element computer code is described that was formulated to analyze single and double lap joints, with and without tapered adherends, and with user-controlled variable element size arrangements. An initial order of Celion 6000/PMR-15 prepreg was received and characterized.

Vortex conception of rotor and mutual effect of screw/propellers

NASA Technical Reports Server (NTRS)

Lepilkin, A. M.

1986-01-01

A vortex theory of screw/propellers with variable circulation according to the blade and its azimuth is proposed, the problem is formulated and circulation is expanded in a Fourier series. Equations are given for inductive velocities in space for crews, including those with an infinitely large number of blades and expansion of the inductive velocity by blade azimuth of a second screw. Multiparameter improper integrals are given as a combination of elliptical integrals and elementary functions, and it is shown how to reduce elliptical integrals of the third kind with a complex parameter to integrals with a real parameter.

Electro-impulse de-icing electrodynamic solution by discrete elements

NASA Technical Reports Server (NTRS)

Bernhart, W. D.; Schrag, R. L.

1988-01-01

This paper describes a technique for analyzing the electrodynamic phenomena associated with electro-impulse deicing. The analysis is done in the time domain and utilizes a discrete element formulation concept expressed in state variable form. Calculated results include coil current, eddy currents in the target (aircraft leading edge skin), pressure distribution on the target, and total force and impulse on the target. Typical results are presented and described. Some comparisons are made between calculated and experimental results, and also between calculated values from other theoretical approaches. Application to the problem of a nonrigid target is treated briefly.

Computing Linear Mathematical Models Of Aircraft

NASA Technical Reports Server (NTRS)

Duke, Eugene L.; Antoniewicz, Robert F.; Krambeer, Keith D.

1991-01-01

Derivation and Definition of Linear Aircraft Model (LINEAR) computer program provides user with powerful, and flexible, standard, documented, and verified software tool for linearization of mathematical models of aerodynamics of aircraft. Intended for use in software tool to drive linear analysis of stability and design of control laws for aircraft. Capable of both extracting such linearized engine effects as net thrust, torque, and gyroscopic effects, and including these effects in linear model of system. Designed to provide easy selection of state, control, and observation variables used in particular model. Also provides flexibility of allowing alternate formulations of both state and observation equations. Written in FORTRAN.

Pharmaceutical quality of "party pills" raises additional safety concerns in the use of illicit recreational drugs.

PubMed

Young, Simon A; Thrimawithana, Thilini R; Antia, Ushtana; Fredatovich, John D; Na, Yonky; Neale, Peter T; Roberts, Amy F; Zhou, Huanyi; Russell, Bruce

2013-06-14

To determine the content and release kinetics of 1-benzylpiperazine (BZP) and 1-(3-trifluoromethyl-phenyl)piperazine (TFMPP) from "party pill" formulations. From these data, the possible impact of pharmaceutical quality upon the safety of such illicit formulations may be inferred. The amount of BZP and TFMPP in party pill formulations was determined using a validated HPLC method. The in-vitro release kinetics of selected party pill brands were determined using a USP dissolution apparatus (75 rpm, 37.5 degrees Celsius). The release data were then fitted to a first order release model using PLOT software and the time taken to achieve 90% release reported. Many of the tested party pill brands contained amounts of BZP and TFMPP that varied considerably from that stated on the packaging; including considerable TFMPP content in some brands not labelled to contain this drug. Dissolution studies revealed that there was considerable variability in the release kinetics between brands; in one case 90% release required >30 minutes. Lack of quality control in party pill manufacture may have led to the toxic effects reported by users unaware of the true content and release of drug from pills. More stringent regulation in the manufacture and quality control of "new generation party pills" is essential to the harm reduction campaign.

Noncontact Infrared-Mediated Heat Transfer During Continuous Freeze-Drying of Unit Doses.

PubMed

Van Bockstal, Pieter-Jan; De Meyer, Laurens; Corver, Jos; Vervaet, Chris; De Beer, Thomas

2017-01-01

Recently, an innovative continuous freeze-drying concept for unit doses was proposed, based on spinning the vials during freezing. An efficient heat transfer during drying is essential to continuously process these spin frozen vials. Therefore, the applicability of noncontact infrared (IR) radiation was examined. The impact of several process and formulation variables on the mass of sublimed ice after 15 min of primary drying (i.e., sublimation rate) and the total drying time was examined. Two experimental designs were performed in which electrical power to the IR heaters, distance between the IR heaters and the spin frozen vial, chamber pressure, product layer thickness, and 5 model formulations were included as factors. A near-infrared spectroscopy method was developed to determine the end point of primary and secondary drying. The sublimation rate was mainly influenced by the electrical power to the IR heaters and the distance between the IR heaters and the vial. The layer thickness had the largest effect on total drying time. The chamber pressure and the 5 model formulations had no significant impact on sublimation rate and total drying time, respectively. This study shows that IR radiation is suitable to provide the energy during the continuous processing of spin frozen vials. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

A Diffuse Interface Model with Immiscibility Preservation

PubMed Central

Tiwari, Arpit; Freund, Jonathan B.; Pantano, Carlos

2013-01-01

A new, simple, and computationally efficient interface capturing scheme based on a diffuse interface approach is presented for simulation of compressible multiphase flows. Multi-fluid interfaces are represented using field variables (interface functions) with associated transport equations that are augmented, with respect to an established formulation, to enforce a selected interface thickness. The resulting interface region can be set just thick enough to be resolved by the underlying mesh and numerical method, yet thin enough to provide an efficient model for dynamics of well-resolved scales. A key advance in the present method is that the interface regularization is asymptotically compatible with the thermodynamic mixture laws of the mixture model upon which it is constructed. It incorporates first-order pressure and velocity non-equilibrium effects while preserving interface conditions for equilibrium flows, even within the thin diffused mixture region. We first quantify the improved convergence of this formulation in some widely used one-dimensional configurations, then show that it enables fundamentally better simulations of bubble dynamics. Demonstrations include both a spherical bubble collapse, which is shown to maintain excellent symmetry despite the Cartesian mesh, and a jetting bubble collapse adjacent a wall. Comparisons show that without the new formulation the jet is suppressed by numerical diffusion leading to qualitatively incorrect results. PMID:24058207

The osmotic virial formulation of the free energy of polymer mixing.

PubMed

Bosse, August W; Douglas, Jack F

2015-09-14

We derive an alternative formulation of the free energy of polymer mixing in terms of an osmotic virial expansion. Starting from a generalized free energy of mixing, and the assumption that the internal energy of mixing is analytic in the polymer composition variable, we demonstrate that the free energy of mixing can be represented as an infinite series in the osmotic virial coefficients. This osmotic virial formulation is consistent with, but more general than, a relationship derived for polymer blends with structured monomers by Dudowicz, Freed, and Douglas [J. Chem. Phys. 116, 9983 (2002)] and Douglas, Dudowicz, and Freed [J. Chem. Phys. 127, 224901 (2007)].

Flexible continuous manufacturing platforms for solid dispersion formulations

NASA Astrophysics Data System (ADS)

Karry-Rivera, Krizia Marie

In 2013 16,000 people died in the US due to overdose from prescription drugs and synthetic narcotics. As of that same year, 90% of new molecular entities in the pharmaceutical drug pipeline are classified as poor water-soluble. The work in this dissertation aims to design, develop and validate platforms that solubilize weak acids and can potentially deter drug abuse. These platforms are based on processing solid dispersions via solvent-casting and hot-melt extrusion methods to produce oral transmucosal films and melt tablets. To develop these platforms, nanocrystalline suspensions and glassy solutions were solvent-casted in the form of films after physicochemical characterizations of drug-excipient interactions and design of experiment approaches. A second order model was fitted to the emulsion diffusion process to predict average nanoparticle size and for process optimization. To further validate the manufacturing flexibility of the formulations, glassy solutions were also extruded and molded into tablets. This process included a systematic quality-by-design (QbD) approach that served to identify the factors affecting the critical quality attributes (CQAs) of the melt tablets. These products, due to their novelty, lack discriminatory performance tests that serve as predictors to their compliance and stability. Consequently, Process Analytical Technology (PAT) tools were integrated into the continuous manufacturing platform for films. Near-infrared (NIR) spectroscopy, including chemical imaging, combined with deconvolution algorithms were utilized for a holistic assessment of the effect of formulation and process variables on the product's CQAs. Biorelevant dissolution protocols were then established to improve the in-vivo in-vitro correlation of the oral transmucosal films. In conclusion, the work in this dissertation supports the delivery of poor-water soluble drugs in products that may deter abuse. Drug nanocrystals ensured high bioavailability, while glassy solutions enabled drug solubilization in polymer matrices. PAT tools helped in characterizing the micro and macro structure of the product while also used as a control strategy for manufacturing. The systematic QbD assessment enabled identification of the variables that significantly affected melt tablet performance and their potential as an abuse deterrent product. Being that these glassy products are novel systems, biorelevant protocols for testing dissolution performance of films were also developed.

A novel in situ hydrophobic ion paring (HIP) formulation strategy for clinical product selection of a nanoparticle drug delivery system.

PubMed

Song, Young Ho; Shin, Eyoung; Wang, Hong; Nolan, Jim; Low, Susan; Parsons, Donald; Zale, Stephen; Ashton, Susan; Ashford, Marianne; Ali, Mir; Thrasher, Daniel; Boylan, Nicholas; Troiano, Greg

2016-05-10

The present studies were aimed at formulating AZD2811-loaded polylactic acid-polyethylene glycol (PLA-PEG) nanoparticles with adjustable release rates without altering the chemical structures of the polymer or active pharmaceutical ingredient (API). This was accomplished through the use of a hydrophobic ion pairing approach. A series of AZD2811-containing nanoparticles with a variety of hydrophobic counterions including oleic acid, 1-hydroxy-2-naphthoic acid, cholic acid, deoxycholic acid, dioctylsulfosuccinic acid, and pamoic acid is described. The hydrophobicity of AZD2811 was increased through formation of ion pairs with these hydrophobic counterions, producing nanoparticles with exceptionally high drug loading-up to five fold higher encapsulation efficiency and drug loading compared to nanoparticles made without hydrophobic ion pairs. Furthermore, the rate at which the drug was released from the nanoparticles could be controlled by employing counterions with various hydrophobicities and structures, resulting in release half-lives ranging from about 2 to 120h using the same polymer, nanoparticle size, and nanoemulsion process. Process recipe variables affecting drug load and release rate were identified, including pH and molarity of quench buffer. Ion pair formation between AZD2811 and pamoic acid as a model counterion was investigated using solubility enhancement as well as nuclear magnetic resonance spectroscopy to demonstrate solution-state interactions. Further evidence for an ion pairing mechanism of controlled release was provided through the measurement of API and counterion release profiles using high-performance liquid chromatography, which had stoichiometric relationships. Finally, Raman spectra of an AZD2811-pamoate salt compared well with those of the formulated nanoparticles, while single components (AZD2811, pamoic acid) alone did not. A library of AZD2811 batches was created for analytical and preclinical characterization. Dramatically improved preclinical efficacy and tolerability data were generated for the pamoic acid lead formulation, which has been selected for evaluation in a Phase 1 clinical trial (ClinicalTrials.gov Identifier NCT 02579226). This work clearly demonstrates the importance of assessing a wide range of drug release rates during formulation screening as a critical step for new drug product development, and how utilizing hydrophobic ion pairing enabled this promising nanoparticle formulation to proceed into clinical development. Copyright © 2016 Elsevier B.V. All rights reserved.

Optimization of methazolamide-loaded solid lipid nanoparticles for ophthalmic delivery using Box-Behnken design.

PubMed

Wang, Fengzhen; Chen, Li; Jiang, Sunmin; He, Jun; Zhang, Xiumei; Peng, Jin; Xu, Qunwei; Li, Rui

2014-09-01

The purpose of the present study was to optimize methazolamide (MTZ)-loaded solid lipid nanoparticles (SLNs) which were used as topical eye drops by evaluating the relationship between design factors and experimental data. A three factor, three-level Box-Behnken design (BBD) was used for the optimization procedure, choosing the amount of GMS, the amount of phospholipid, the concentration of surfactant as the independent variables. The chosen dependent variables were entrapment efficiency, dosage loading, and particle size. The generated polynomial equations and response surface plots were used to relate the dependent and independent variables. The optimal nanoparticles were formulated with 100 mg GMS, 150 mg phospholipid, and 1% Tween80 and PEG 400 (1:1, w/v). A new formulation was prepared according to these levels. The observed responses were close to the predicted values of the optimized formulation. The particle size was 197.8 ± 4.9 nm. The polydispersity index of particle size was 0.239 ± 0.01 and the zeta potential was 32.7 ± 2.6 mV. The entrapment efficiency and dosage loading were about 68.39% and 2.49%, respectively. Fourier transform infrared spectroscopy (FT-IR) study indicated that the drug was entrapped in nanoparticles. The optimized formulation showed a sustained release followed the Peppas model. MTZ-SLNs showed significant prolonged decreasing intraocular pressure effect comparing with MTZ solution in vivo pharmacodynamics studies. The results of acute eye irritation study indicated that MTZ-SLNs and AZOPT both had no eye irritation. Furthermore, the MTZ-SLNs were suitable to be stored at low temperature (4 °C).

Contemporary formulation and distribution practices for cold-filled acid products: Australian industry survey and modeling of published pathogen inactivation data.

PubMed

Chapman, B; Scurrah, K J; Ross, T

2010-05-01

A survey of 12 Australian manufacturers indicated that mild-tasting acids and preservatives are used to partially replace acetic acid in cold-filled acid dressings and sauces. In contrast to traditional ambient temperature distribution practices, some manufacturers indicated that they supply the food service sector with cold-filled acid products prechilled for incorporation into ready-to-eat foods. The Comité des Industries des Mayonnaises et Sauces Condimentaires de la Communauté Economique Européenne (CIMSCEE) Code, a formulation guideline used by the industry to predict the safety of cold-filled acid formulations with respect to Salmonella enterica and Escherichia coli, does not extend to the use of acids and preservatives other than acetic acid nor does it consider the effects of chill distribution. We found insufficient data in the published literature to comprehensively model the response of S. enterica and E. coli to all of the predictor variables (i.e., pH, acetic acid, NaCl, sugars, other acids, preservatives, and storage temperature) of relevance for contemporary cold-filled acid products in Australia. In particular, we noted a lack of inactivation data for S. enterica at aqueous-phase NaCl concentrations of >3% (wt/wt). However, our simple models clearly identified pH and 1/absolute temperature of storage as the most important variables generally determining inactivation. To develop robust models to predict the effect of contemporary formulation and storage variables on product safety, additional empirical data are required. Until such models are available, our results support challenge testing of cold-filled acid products to ascertain their safety, as suggested by the CIMSCEE, but suggest consideration of challenging with both E. coli and S. enterica at incubation temperatures relevant to intended product distribution temperatures.

Optimization and characterization of spray-dried IgG formulations: a design of experiment approach.

PubMed

Faghihi, Homa; Najafabadi, Abdolhosein Rouholamini; Vatanara, Alireza

2017-10-24

The purpose of the present study is to optimize a spray-dried formulation as a model antibody regarding stability and aerodynamic property for further aerosol therapy of this group of macromolecules. A three-factor, three-level, Box-Behnken design was employed milligrams of Cysteine (X 1 ), Trehalose (X 2 ), and Tween 20 (X 3 ) as independent variables. The dependent variables were quantified and the optimized formulation was prepared accordingly. SEC-HPLC and FTIR-spectroscopy were conducted to evaluate the molecular and structural status of spray-dried preparations. Particle characterization of optimized sample was performed with the aid of DSC, SEM, and TSI examinations. Experimental responses of a total of 17 formulations resulted in yield values, (Y 1 ), ranging from 21.1 ± 0.2 to 40.2 ± 0.1 (%); beta-sheet content, (Y 2 ), from 66.22 ± 0.19 to 73.78 ± 0.26 (%); amount of aggregation following process, (Y 3 ), ranging from 0.11 ± 0.03 to 0.95 ± 0.03 (%); and amount of aggregation upon storage, (Y 4 ), from 0.81 ± 0.01 to 3.13 ± 0.64 (%) as dependent variables. Results-except for those of the beta sheet content-were fitted to quadratic models describing the inherent relationship between main factors. Co-application of Cysteine and Tween 20 preserved antibody molecules from molecular degradation and improved immediate and accelerated stability of spry-dried antibodies. Validation of the optimization study indicated high degree of prognostic ability of response surface methodology in preparation of stable spray-dried IgG. Graphical abstract Spray drying of IgG in the presence of Trehalose, Cysteine and Tween 20.

Brain-targeted intranasal zaleplon solid dispersion in hydrophilic carrier system; 23 full-factorial design and in vivo determination of GABA neurotransmitter.

PubMed

Abd-Elrasheed, Eman; Nageeb El-Helaly, Sara; El-Ashmoony, Manal M; Salah, Salwa

2018-05-01

Intranasal zaleplon solid dispersion was formulated to enhance the solubility, bioavailability and deliver an effective therapy. Zaleplon belongs to Class II drugs, and undergoes extensive first-pass metabolism after oral absorption exhibiting 30% bioavailability. A 2 3 full-factorial design was chosen for the investigation of solid dispersion formulations. The effects of different variables include drug to carrier ratio (1:1 and 1:2), carrier type (polyethylene glycol 4000 and poloxamer 407), and preparation method (solvent evaporation and freeze drying) on different dissolution parameters were studied. The dependent variables determined from the in vitro characterization and their constraints were set as follows: minimum mean dissolution time, maximum dissolution efficiency and maximum percentage release. Numerical optimization was performed according to the constraints set based on the utilization of desirability functions. Differential scanning calorimetry, infrared spectroscopy, X-ray diffraction and scanning electron microscopy were performed. Ex vivo estimation of nasal cytotoxicity and assessment of the γ-aminobutyric acid level in plasma and brain 1 h after nasal SD administration in rabbits compared to the oral market product were conducted. The selected ZP-SD, with a desirability 0.9, composed of poloxamer 407 at drug to carrier ratio 1:2 successfully enhanced the bioavailability showing 44% increase in GABA concentration than the marketed tablets.

Pharmacokinetics of a once-daily extended-release formulation of pramipexole in healthy male volunteers: three studies.

PubMed

Jenner, Peter; Könen-Bergmann, Michael; Schepers, Cornelia; Haertter, Sebastian

2009-11-01

Pramipexole is a dopamine agonist used in the treatment of Parkinson's disease. The currently available immediate-release (IR) formulation is taken orally 3 times daily. These studies were conducted to evaluate the pharmacokinetic properties of a variety of prototypes for a once-daily extended-release (ER) formulation of pramipexole and to further characterize the prototype whose pharmacokinetics best matched those of the IR formulation. Three Phase I studies were conducted, all in healthy adult men aged

Formulation of topical bioadhesive gel of aceclofenac using 3-level factorial design.

PubMed

Singh, Sanjay; Parhi, Rabinarayan; Garg, Anuj

2011-01-01

The objective of this work was to develop bioadhesive topical gel of Aceclofenac with the help of response-surface approach. Experiments were performed according to a 3-level factorial design to evaluate the effects of two independent variables [amount of Poloxamer 407 (PL-407 = X1) and hydroxypropylmethyl cellulose K100 M (HPMC = X2)] on the bioadhesive character of gel, rheological property of gel (consistency index), and in-vitro drug release. The best model was selected to fit the data. Mathematical equation was generated by Design Expert® software for the model which assists in determining the effect of independent variables. Response surface plots were also generated by the software for analyzing effect of the independent variables on the response. Quadratic model was found to be the best for all the responses. Both independent variable (X1 and X2) were found to have synergistic effect on bioadhesion (Y1) but the effect of HPMC was more pronounced than PL-407. Consistency index was enhanced by increasing the level of both independent variables. An antagonistic effect of both independent variables was found on cumulative percentage release of drug in 2 (Y3) and 8 h (Y4). Both independent variables approximately equally contributed the antagonistic effect on Y3 whereas antagonistic effect of HPMC was more pronounced than PL-407. The effect of formulation variables on the product characteristics can be easily predicted and precisely interpreted by using a 3-level factorial experimental design and generated quadratic mathematical equations.

Load estimator (LOADEST): a FORTRAN program for estimating constituent loads in streams and rivers

USGS Publications Warehouse

Runkel, Robert L.; Crawford, Charles G.; Cohn, Timothy A.

2004-01-01

LOAD ESTimator (LOADEST) is a FORTRAN program for estimating constituent loads in streams and rivers. Given a time series of streamflow, additional data variables, and constituent concentration, LOADEST assists the user in developing a regression model for the estimation of constituent load (calibration). Explanatory variables within the regression model include various functions of streamflow, decimal time, and additional user-specified data variables. The formulated regression model then is used to estimate loads over a user-specified time interval (estimation). Mean load estimates, standard errors, and 95 percent confidence intervals are developed on a monthly and(or) seasonal basis. The calibration and estimation procedures within LOADEST are based on three statistical estimation methods. The first two methods, Adjusted Maximum Likelihood Estimation (AMLE) and Maximum Likelihood Estimation (MLE), are appropriate when the calibration model errors (residuals) are normally distributed. Of the two, AMLE is the method of choice when the calibration data set (time series of streamflow, additional data variables, and concentration) contains censored data. The third method, Least Absolute Deviation (LAD), is an alternative to maximum likelihood estimation when the residuals are not normally distributed. LOADEST output includes diagnostic tests and warnings to assist the user in determining the appropriate estimation method and in interpreting the estimated loads. This report describes the development and application of LOADEST. Sections of the report describe estimation theory, input/output specifications, sample applications, and installation instructions.

Imported infections: What information should be collected by surveillance systems to inform public health policy?

PubMed

Neave, Penny E; Heywood, Anita E; Gibney, Katherine B; Leder, Karin

2016-01-01

International travel carries the risk of imported diseases, which are an increasingly significant public health problem. There is little guidance about which variables should be collected by surveillance systems for strategy-based surveillance. Surveillance forms for dengue, malaria, hepatitis A, typhoid and measles were collected from Australia and New Zealand and information on these compared with national surveillance forms from the UK and Canada by travel health experts. Variables were categorised by information relating to recent travel, demographics and disease severity. Travel-related information most commonly requested included country of travel, vaccination status and travel dates. In Australia, ethnicity information requested related to indigenous status, whilst in New Zealand it could be linked to census categories. Severity of disease information most frequently collected were hospitalisation and death. Reviewing the usefulness of variables collected resulted in the recommendation that those included should be: overseas travel, reason for travel, entry and departure dates during the incubation period, vaccination details, traveller's and/or parents' country of birth, country of usual residence, time resident in current country, postcode, hospitalisation and death details. There was no agreement about whether ethnicity details should be collected. The inclusion of these variables on surveillance forms could enable imported infection-related policy to be formulated nationally and internationally. Copyright © 2016 Elsevier Ltd. All rights reserved.

A new fractional operator of variable order: Application in the description of anomalous diffusion

NASA Astrophysics Data System (ADS)

Yang, Xiao-Jun; Machado, J. A. Tenreiro

2017-09-01

In this paper, a new fractional operator of variable order with the use of the monotonic increasing function is proposed in sense of Caputo type. The properties in term of the Laplace and Fourier transforms are analyzed and the results for the anomalous diffusion equations of variable order are discussed. The new formulation is efficient in modeling a class of concentrations in the complex transport process.

Qualitative and Quantitative Assessment of Four Marketed Formulations of Brahmi

PubMed Central

Saini, Neeti; Mathur, Rajani; Agrawal, S. S.

2012-01-01

This study was conducted with the aim to compare two batches each of four popular commercial formulations of Bacopa monnieri (Brahmi), and report, if any, inter-batch variations. The formulations were procured from local market and analyzed for label specifications, uniformity of weight of capsule, identity, purity and strength parameters (total ash content test, acid insoluble ash content, water soluble extractive, alcohol soluble extractive, loss on drying). Bacoside A, one of the pharmacologically active saponin present in B. monnieri, was quantified in all the formulations using UV-spectrophotometer. In addition each formulation was assessed and compared for variation in biological activity using in vitro test for hemolytic activity using human erythrocytes. The results of the study show that there is a wide variation in the quality and content of herbal drugs marketed by different manufacturers. More importantly this study demonstrates that there exists a bigger challenge of batch-to-batch variation in the quality and content of herbal formulations of the same manufacturer. This challenge of providing standardized formulations is being faced by not any one manufacturing house but by all, and may be attributed firstly to, lack of stringent regulations and secondly to high variability in raw material quality. PMID:23204618

Qualitative and quantitative assessment of four marketed formulations of brahmi.

PubMed

Saini, Neeti; Mathur, Rajani; Agrawal, S S

2012-01-01

This study was conducted with the aim to compare two batches each of four popular commercial formulations of Bacopa monnieri (Brahmi), and report, if any, inter-batch variations. The formulations were procured from local market and analyzed for label specifications, uniformity of weight of capsule, identity, purity and strength parameters (total ash content test, acid insoluble ash content, water soluble extractive, alcohol soluble extractive, loss on drying). Bacoside A, one of the pharmacologically active saponin present in B. monnieri, was quantified in all the formulations using UV-spectrophotometer. In addition each formulation was assessed and compared for variation in biological activity using in vitro test for hemolytic activity using human erythrocytes. The results of the study show that there is a wide variation in the quality and content of herbal drugs marketed by different manufacturers. More importantly this study demonstrates that there exists a bigger challenge of batch-to-batch variation in the quality and content of herbal formulations of the same manufacturer. This challenge of providing standardized formulations is being faced by not any one manufacturing house but by all, and may be attributed firstly to, lack of stringent regulations and secondly to high variability in raw material quality.

Formulation of multiparticulate systems as lyophilised orally disintegrating tablets.

PubMed

Alhusban, Farhan; Perrie, Yvonne; Mohammed, Afzal R

2011-11-01

The current study aimed to exploit the electrostatic associative interaction between carrageenan and gelatin to optimise a formulation of lyophilised orally disintegrating tablets (ODTs) suitable for multiparticulate delivery. A central composite face centred (CCF) design was applied to study the influence of formulation variables (gelatin, carrageenan and alanine concentrations) on the crucial responses of the formulation (disintegration time, hardness, viscosity and pH). The disintegration time and viscosity were controlled by the associative interaction between gelatin and carrageenan upon hydration which forms a strong complex that increases the viscosity of the stock solution and forms tablet with higher resistant to disintegration in aqueous medium. Therefore, the levels of carrageenan, gelatin and their interaction in the formulation were the significant factors. In terms of hardness, increasing gelatin and alanine concentration was the most effective way to improve tablet hardness. Accordingly, optimum concentrations of these excipients were needed to find the best balance that fulfilled all formulation requirements. The revised model showed high degree of predictability and optimisation reliability and therefore was successful in developing an ODT formulation with optimised properties that were able deliver enteric coated multiparticulates of omeprazole without compromising their functionality. Copyright © 2011 Elsevier B.V. All rights reserved.

Linear programming: an alternative approach for developing formulations for emergency food products.

PubMed

Sheibani, Ershad; Dabbagh Moghaddam, Arasb; Sharifan, Anousheh; Afshari, Zahra

2018-03-01

To minimize the mortality rates of individuals affected by disasters, providing high-quality food relief during the initial stages of an emergency is crucial. The goal of this study was to develop a formulation for a high-energy, nutrient-dense prototype using linear programming (LP) model as a novel method for developing formulations for food products. The model consisted of the objective function and the decision variables, which were the formulation costs and weights of the selected commodities, respectively. The LP constraints were the Institute of Medicine and the World Health Organization specifications of the content of nutrients in the product. Other constraints related to the product's sensory properties were also introduced to the model. Nonlinear constraints for energy ratios of nutrients were linearized to allow their use in the LP. Three focus group studies were conducted to evaluate the palatability and other aspects of the optimized formulation. New constraints were introduced to the LP model based on the focus group evaluations to improve the formulation. LP is an appropriate tool for designing formulations of food products to meet a set of nutritional requirements. This method is an excellent alternative to the traditional 'trial and error' method in designing formulations. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Utilization of a modified special-cubic design and an electronic tongue for bitterness masking formulation optimization.

PubMed

Li, Lianli; Naini, Venkatesh; Ahmed, Salah U

2007-10-01

A unique modification of simplex design was applied to an electronic tongue (E-Tongue) analysis in bitterness masking formulation optimization. Three formulation variables were evaluated in the simplex design, i.e. concentrations of two taste masking polymers, Amberlite and Carbopol, and pH of the granulating fluid. Response of the design was a bitterness distance measured using an E-Tongue by applying a principle component analysis, which represents taste masking efficiency of the formulation. The smaller the distance, the better the bitterness masking effect. Contour plots and polynomial equations of the bitterness distance response were generated as a function of formulation composition and pH. It was found that interactions between polymer and pH reduced the bitterness of the formulation, attributed to pH-dependent ionization and complexation properties of the ionic polymers, thus keeping the drug out of solution and unavailable to bitterness perception. At pH 4.9 and an Amberlite/Carbopol ratio of 1.4:1 (w/w), the optimal taste masking formulation was achieved and in agreement with human gustatory sensation study results. Therefore, adopting a modified simplex experimental design on response measured using an E-Tongue provided an efficient approach to taste masking formulation optimization using ionic binding polymers. (c) 2007 Wiley-Liss, Inc.

Application of non-attenuating frequency radars for prediction of rain attenuation and space diversity performance

NASA Technical Reports Server (NTRS)

Goldhirsh, J.

1979-01-01

In order to establish transmitter power and receiver sensitivity levels at frequencies above 10 GHz, the designers of earth-satellite telecommunication systems are interested in cumulative rain fade statistics at variable path orientations, elevation angles, climatological regions, and frequencies. They are also interested in establishing optimum space diversity performance parameters. In this work are examined the many elements involved in the employment of single non-attenuating frequency radars for arriving at the desired information. The elements examined include radar techniques and requirements, phenomenological assumptions, path attenation formulations and procedures, as well as error budgeting and calibration analysis. Included are the pertinent results of previous investigators who have used radar for rain attenuation modeling. Suggestions are made for improving present methods.

Structure-Property Relationships of Architectural Coatings by Neutron Methods

NASA Astrophysics Data System (ADS)

Nakatani, Alan

2015-03-01

Architectural coatings formulations are multi-component mixtures containing latex polymer binder, pigment, rheology modifiers, surfactants, and colorants. In order to achieve the desired flow properties for these formulations, measures of the underlying structure of the components as a function of shear rate and the impact of formulation variables on the structure is necessary. We have conducted detailed measurements to understand the evolution under shear of local microstructure and larger scale mesostructure in model architectural coatings formulations by small angle neutron scattering (SANS) and ultra small angle neutron scattering (USANS), respectively. The SANS results show an adsorbed layer of rheology modifier molecules exist on the surface of the latex particles. However, the additional hydrodynamic volume occupied by the adsorbed surface layer is insufficient to account for the observed viscosity by standard hard sphere suspension models (Krieger-Dougherty). The USANS results show the presence of latex aggregates, which are fractal in nature. These fractal aggregates are the primary structures responsible for coatings formulation viscosity. Based on these results, a new model for the viscosity of coatings formulations has been developed, which is capable of reproducing the observed viscosity behavior.

Single-dose oral pharmacokinetics of three formulations of thalidomide in healthy male volunteers.

PubMed

Teo, S K; Colburn, W A; Thomas, S D

1999-11-01

Thalidomide was recently approved in the United States for the treatment of erythema nodosum leprosum, a complication of leprosy. The present study determined the bioequivalence and pharmacokinetics of Celgene's commercial and clinical trial thalidomide formulations and the Brazilian Tortuga formulation in an open-label, single-dose, three-way crossover design. Seventeen healthy subjects were given 200 mg of thalidomide on three occasions, and blood samples were collected over 48 hours. Pharmacokinetic parameters were determined using compartmental methods for the two Celgene formulations and using noncompartmental methods for all three formulations. All subjects reported adverse events, none of which was serious or unexpected. Celgene formulations were bioequivalent when comparing Cmax, tmax, and AUC. There was significant variability in plasma levels from the Tortuga formulation, giving a mean profile that was distinctly different from the two Celgene formulations with a lower Cmax value and a longer terminal phase. The lower Cmax was probably due to slower absorption. The terminal rate constant for the Tortuga formulation was significantly less, giving rise to a terminal half-life of 15 hours compared to about 5 to 6 hours for the Celgene formulations. Confidence intervals for Cmax between the Tortuga and the Celgene formulations were outside the 80% to 125% range, indicating a lack of bioequivalence. Extent of absorption, as measured by AUC0-infinity, was approximately equal for all three formulations. Terminal half-life for Tortuga was two to three times longer compared to the Celgene formulations and is clear evidence for absorption rate limitations. The two Celgene formulations showed similar pharmacokinetic parameters with profiles that were best described by a one-compartment model with first-order absorption and elimination. The authors conclude that Celgene's clinical trial and commercial thalidomide formulations are similar to each other and distinctly different from the Tortuga formulation and that all three formulations exhibited absorption rate-limited elimination.

Audible acoustics in high-shear wet granulation: application of frequency filtering.

PubMed

Hansuld, Erin M; Briens, Lauren; McCann, Joe A B; Sayani, Amyn

2009-08-13

Previous work has shown analysis of audible acoustic emissions from high-shear wet granulation has potential as a technique for end-point detection. In this research, audible acoustic emissions (AEs) from three different formulations were studied to further develop this technique as a process analytical technology. Condenser microphones were attached to three different locations on a PMA-10 high-shear granulator (air exhaust, bowl and motor) to target different sound sources. Size, flowability and tablet break load data was collected to support formulator end-point ranges and interpretation of AE analysis. Each formulation had a unique total power spectral density (PSD) profile that was sensitive to granule formation and end-point. Analyzing total PSD in 10 Hz segments identified profiles with reduced run variability and distinct maxima and minima suitable for routine granulation monitoring and end-point control. A partial least squares discriminant analysis method was developed to automate selection of key 10 Hz frequency groups using variable importance to projection. The results support use of frequency refinement as a way forward in the development of acoustic emission analysis for granulation monitoring and end-point control.

Explicit finite-volume time-marching calculations of total temperature distributions in turbulent flow

NASA Technical Reports Server (NTRS)

Nicholson, Stephen; Moore, Joan G.; Moore, John

1987-01-01

A method was developed which calculates two-dimensional, transonic, viscous flow in ducts. The finite volume, time-marching formulation is used to obtain steady flow solutions of the Reynolds-averaged form of the Navier-Stokes equations. The entire calculation is performed in the physical domain. This paper investigates the introduction of a new formulation of the energy equation which gives improved transient behavior as the calculation converges. The effect of variable Prandtl number on the temperature distribution through the boundary layer is also investigated. A turbulent boundary layer in an adverse pressure gradient (M = 0.55) is used to demonstrate the improved transient temperature distribution obtained when the new formulation of the energy equation is used. A flat plate turbulent boundary layer with a supersonic free-stream Mach number of 2.8 is used to investigate the effect of Prandtl number on the distribution of properties through the boundary layer. The computed total temperature distribution and recovery factor agree well with the measurements when a variable Prandtl number is used through the boundary layer.

Explicit finite-volume time-marching calculations of total temperature distributions in turbulent flow

NASA Technical Reports Server (NTRS)

Nicholson, Stephen; Moore, Joan G.; Moore, John

1986-01-01

A method was developed which calculates two-dimensional, transonic, viscous flow in ducts. The finite volume, time-marching formulation is used to obtain steady flow solutions of the Reynolds-averaged form of the Navier-Stokes equations. The entire calculation is performed in the physical domain. This paper investigates the introduction of a new formulation of the energy equation which gives improved transient behavior as the calculation converges. The effect of variable Prandtl number on the temperature distribution through the boundary layer is also investigated. A turbulent boundary layer in an adverse pressure gradient (M = 0.55) is used to demonstrate the improved transient temperature distribution obtained when the new formulation of the energy equation is used. A flat plate turbulent boundary layer with a supersonic free-stream Mach number of 2.8 is used to investigate the effect of Prandtl number on the distribution of properties through the boundary layer. The computed total temperature distribution and recovery factor agree well with the measurements when a variable Prandtl number is used through the boundary layer.

Description and validation of the Simple, Efficient, Dynamic, Global, Ecological Simulator (SEDGES v.1.0)

NASA Astrophysics Data System (ADS)

Paiewonsky, Pablo; Elison Timm, Oliver

2018-03-01

In this paper, we present a simple dynamic global vegetation model whose primary intended use is auxiliary to the land-atmosphere coupling scheme of a climate model, particularly one of intermediate complexity. The model simulates and provides important ecological-only variables but also some hydrological and surface energy variables that are typically either simulated by land surface schemes or else used as boundary data input for these schemes. The model formulations and their derivations are presented here, in detail. The model includes some realistic and useful features for its level of complexity, including a photosynthetic dependency on light, full coupling of photosynthesis and transpiration through an interactive canopy resistance, and a soil organic carbon dependence for bare-soil albedo. We evaluate the model's performance by running it as part of a simple land surface scheme that is driven by reanalysis data. The evaluation against observational data includes net primary productivity, leaf area index, surface albedo, and diagnosed variables relevant for the closure of the hydrological cycle. In this setup, we find that the model gives an adequate to good simulation of basic large-scale ecological and hydrological variables. Of the variables analyzed in this paper, gross primary productivity is particularly well simulated. The results also reveal the current limitations of the model. The most significant deficiency is the excessive simulation of evapotranspiration in mid- to high northern latitudes during their winter to spring transition. The model has a relative advantage in situations that require some combination of computational efficiency, model transparency and tractability, and the simulation of the large-scale vegetation and land surface characteristics under non-present-day conditions.

The impact of manufacturing variables on in vitro release of clobetasol 17-propionate from pilot scale cream formulations.

PubMed

Fauzee, Ayeshah Fateemah Beebee; Khamanga, Sandile Maswazi; Walker, Roderick Bryan

2014-12-01

The purpose of the study was to evaluate the effect of different homogenization speeds and times, anchor speeds and cooling times on the viscosity and cumulative % clobetasol 17-propionate released per unit area at 72 h from pilot scale cream formulations. A 2(4) full factorial central composite design for four independent variables were investigated. Thirty pilot scale batches of cream formulations were manufactured using a Wintech® cream/ointment plant. The viscosity and in vitro release of CP were monitored and compared to an innovator product that is commercially available on the South African market, namely, Dermovate® cream. Contour and three-dimensional response surface plots were produced and the viscosity and cumulative % CP released per unit area at 72 h were found to be primarily dependent on the homogenization and anchor speeds. An increase in the homogenization and anchor speeds appeared to exhibit a synergistic effect on the resultant viscosity of the cream whereas an antagonistic effect was observed for the in vitro release of CP from the experimental cream formulations. The in vitro release profiles were best fitted to a Higuchi model and diffusion proved to be the dominant mechanism of drug release that was confirmed by use of the Korsmeyer-Peppas model. The research was further validated and confirmed by the high prognostic ability of response surface methodology (RSM) with a resultant mean percentage error of (±SD) 0.17 ± 0.093 suggesting that RSM may be an efficient tool for the development and optimization of topical formulations.

A pocket of variability in Pinus rigida

Treesearch

F. Thomas Ledig; John H. Fryer

1971-01-01

Steady state gene frequencies around a pocket of differential fitness have been formulated by Hanson (1966) in a generalization of the work of Haldane (1948). A pocket of differential fitness would result in a pocket-of-variability, assuming that the radius of the area of contrasting fitness was large in relation to the vagility of the organism. Conversely, the absence...

Formulation and In-vitro Characterization of Sustained Release Matrix Type Ocular Timolol Maleate Mini-Tablet

PubMed Central

Mortazavi, Seyed Alireza; Jafariazar, Zahra; Ghadjahani, Yasaman; Mahmoodi, Hoda; Mehtarpour, Farzaneh

2014-01-01

The purpose of this study was preparation and evaluation of sustained release matrix type ocular mini-tablets of timolol maleate, as a potential formulation for the treatment of glaucoma. Following the initial studies on timolol maleate powder, it was formulated into ocular mini-tablets. The polymers investigated in this study included cellulose derivatives (HEC, CMC, EC) and Carbopol 971P. Mannitol was used as the solubilizing agent and magnesium stearate as the lubricant. Mini-tablets were prepared by through mixing of the ingredients, followed by direct compression. All the prepared formulations were evaluated in terms of physicochemical tests, including uniformity of weight, thickness, crushing strength, friability and in-vitro drug release. Four groups of formulations were prepared. The presence of different amounts of cellulose derivatives or Carbopol 971P, alone, was studied in group A formulations. In group B formulations, the effect of adding Carbopol 971P alongside different cellulose derivatives was investigated. Group C formulations were made by including mannitol as the solubilizing agent, alongside Carbopol 971P and a cellulose derivative. In group D formulations, mini-tablets were made using Carbopol 971P, alongside two different cellulose derivative. The selected formulation (C1) contained ethyl cellulose, Carbopol 971P, mannitol and magnesium stearate, which showed almost 100% drug release over 5 h. Based on kinetic studies, this formulation was found to best fit the zero-order model of drug release. However, the Higuchi and Hixson -Crowell models also showed a good fit. Hence, overall, formulation C1 was chosen as the best formulation. PMID:24734053

Development of a vaginal delivery film containing EFdA, a novel anti-HIV nucleoside reverse transcriptase inhibitor

PubMed Central

Zhang, Wei; Parniak, Michael A.; Sarafianos, Stefan G.; Cost, Marilyn R.; Rohan, Lisa C.

2014-01-01

The aim of this work was to develop a fast-dissolving film formulation containing EFdA for potential use as a topical vaginal microbicide for prevention of HIV sexual transmission. Solid state compatibility approaches were used to screen commonly used polymers for formulation development. Factorial design and desirability function were used to investigate the effect of two variables, the ratio of the polymers and the concentration of selected plasticizer on four mechanical responses including tensile strength, elongation at break, toughness and elastic modulus for optimization of the film formulation. Assessments of EFdA-loaded films included physicochemical characteristics, in vitro cytotoxicity, epithelia integrity, ex vivo permeability and bioactivity test. The optimal placebo film was composed of PVA, HPMC E5 and propylene glycol (7:3:3, w/w), and its mechanical characteristics were comparable to those of VCF® film (a commercial vaginal film product). Permeability studies using human ectocervical explants showed that there was no significant difference in cumulative permeated amount of EFdA between EFdA film and free EFdA. The results of in vitro cytotoxicity and bioactivity testing showed that 50% cytotoxic concentration (CC50) was several orders of magnitude higher than 50% effective concentration (EC50) of EFdA. Furthermore, epithelial integrity study showed that EFdA-loaded film had a much lower toxicity to HEC-1A cell monolayers as compared to VCF®. Therefore, EFdA-loaded vaginal film may be considered as a promising vaginal microbicide for HIV prevention. PMID:24333452

An entropy-variables-based formulation of residual distribution schemes for non-equilibrium flows

NASA Astrophysics Data System (ADS)

Garicano-Mena, Jesús; Lani, Andrea; Degrez, Gérard

2018-06-01

In this paper we present an extension of Residual Distribution techniques for the simulation of compressible flows in non-equilibrium conditions. The latter are modeled by means of a state-of-the-art multi-species and two-temperature model. An entropy-based variable transformation that symmetrizes the projected advective Jacobian for such a thermophysical model is introduced. Moreover, the transformed advection Jacobian matrix presents a block diagonal structure, with mass-species and electronic-vibrational energy being completely decoupled from the momentum and total energy sub-system. The advantageous structure of the transformed advective Jacobian can be exploited by contour-integration-based Residual Distribution techniques: established schemes that operate on dense matrices can be substituted by the same scheme operating on the momentum-energy subsystem matrix and repeated application of scalar scheme to the mass-species and electronic-vibrational energy terms. Finally, the performance gain of the symmetrizing-variables formulation is quantified on a selection of representative testcases, ranging from subsonic to hypersonic, in inviscid or viscous conditions.

Time-variant Lagrangian transport formulation reduces aggregation bias of water and solute mean travel time in heterogeneous catchments

NASA Astrophysics Data System (ADS)

Danesh-Yazdi, Mohammad; Botter, Gianluca; Foufoula-Georgiou, Efi

2017-05-01

Lack of hydro-bio-chemical data at subcatchment scales necessitates adopting an aggregated system approach for estimating water and solute transport properties, such as residence and travel time distributions, at the catchment scale. In this work, we show that within-catchment spatial heterogeneity, as expressed in spatially variable discharge-storage relationships, can be appropriately encapsulated within a lumped time-varying stochastic Lagrangian formulation of transport. This time (variability) for space (heterogeneity) substitution yields mean travel times (MTTs) that are not significantly biased to the aggregation of spatial heterogeneity. Despite the significant variability of MTT at small spatial scales, there exists a characteristic scale above which the MTT is not impacted by the aggregation of spatial heterogeneity. Extensive simulations of randomly generated river networks reveal that the ratio between the characteristic scale and the mean incremental area is on average independent of river network topology and the spatial arrangement of incremental areas.

A four-lens based plenoptic camera for depth measurements

NASA Astrophysics Data System (ADS)

Riou, Cécile; Deng, Zhiyuan; Colicchio, Bruno; Lauffenburger, Jean-Philippe; Kohler, Sophie; Haeberlé, Olivier; Cudel, Christophe

2015-04-01

In previous works, we have extended the principles of "variable homography", defined by Zhang and Greenspan, for measuring height of emergent fibers on glass and non-woven fabrics. This method has been defined for working with fabric samples progressing on a conveyor belt. Triggered acquisition of two successive images was needed to perform the 3D measurement. In this work, we have retained advantages of homography variable for measurements along Z axis, but we have reduced acquisitions number to a single one, by developing an acquisition device characterized by 4 lenses placed in front of a single image sensor. The idea is then to obtain four projected sub-images on a single CCD sensor. The device becomes a plenoptic or light field camera, capturing multiple views on the same image sensor. We have adapted the variable homography formulation for this device and we propose a new formulation to calculate a depth with plenoptic cameras. With these results, we have transformed our plenoptic camera in a depth camera and first results given are very promising.

A mass-conserving mixed Fourier-Galerkin B-Spline-collocation method for Direct Numerical Simulation of the variable-density Navier-Stokes equations

NASA Astrophysics Data System (ADS)

Reuter, Bryan; Oliver, Todd; Lee, M. K.; Moser, Robert

2017-11-01

We present an algorithm for a Direct Numerical Simulation of the variable-density Navier-Stokes equations based on the velocity-vorticity approach introduced by Kim, Moin, and Moser (1987). In the current work, a Helmholtz decomposition of the momentum is performed. Evolution equations for the curl and the Laplacian of the divergence-free portion are formulated by manipulation of the momentum equations and the curl-free portion is reconstructed by enforcing continuity. The solution is expanded in Fourier bases in the homogeneous directions and B-Spline bases in the inhomogeneous directions. Discrete equations are obtained through a mixed Fourier-Galerkin and collocation weighted residual method. The scheme is designed such that the numerical solution conserves mass locally and globally by ensuring the discrete divergence projection is exact through the use of higher order splines in the inhomogeneous directions. The formulation is tested on multiple variable-density flow problems.

Fat substitutes in processing of sausages using piramutaba waste.

PubMed

de Fátima Henriques Lourenço, Lúcia; Dos Santos Galvão, Giane Célia; da Conceição Amaral Ribeiro, Suezilde; de Fátima Amaral Ribeiro, Carmelita; Park, Kil Jin

2014-07-01

The aim of this study was to evaluate fat substitute in processing of sausages prepared with surimi of waste from piramutaba filleting. The formulation ingredients were mixed with the fat substitutes added according to a fractional planning 2(4-1), where the independent variables, manioc starch (Ms), hydrogenated soy fat (F), texturized soybean protein (Tsp) and carrageenan (Cg) were evaluated on the responses of pH, texture (Tx), raw batter stability (RBS) and water holding capacity (WHC) of the sausage. Fat substitutes were evaluated in 11 formulations and the results showed that the greatest effects on the responses were found to Ms, F and Cg, being eliminated from the formulation Tsp. To find the best formulation for processing piramutaba sausage was made a complete factorial planning of 2(3) to evaluate the concentrations of fat substitutes in an enlarged range. The optimum condition found for fat substitutes in the sausages formulation were carrageenan (0.51%), manioc starch (1.45%) and fat (1.2%).

Development and application of a validated HPLC method for the analysis of dissolution samples of levothyroxine sodium drug products.

PubMed

Collier, J W; Shah, R B; Bryant, A R; Habib, M J; Khan, M A; Faustino, P J

2011-02-20

A rapid, selective, and sensitive gradient HPLC method was developed for the analysis of dissolution samples of levothyroxine sodium tablets. Current USP methodology for levothyroxine (L-T(4)) was not adequate to resolve co-elutants from a variety of levothyroxine drug product formulations. The USP method for analyzing dissolution samples of the drug product has shown significant intra- and inter-day variability. The sources of method variability include chromatographic interferences introduced by the dissolution media and the formulation excipients. In the present work, chromatographic separation of levothyroxine was achieved on an Agilent 1100 Series HPLC with a Waters Nova-pak column (250 mm × 3.9 mm) using a 0.01 M phosphate buffer (pH 3.0)-methanol (55:45, v/v) in a gradient elution mobile phase at a flow rate of 1.0 mL/min and detection UV wavelength of 225 nm. The injection volume was 800 μL and the column temperature was maintained at 28°C. The method was validated according to USP Category I requirements. The validation characteristics included accuracy, precision, specificity, linearity, and analytical range. The standard curve was found to have a linear relationship (r(2)>0.99) over the analytical range of 0.08-0.8 μg/mL. Accuracy ranged from 90 to 110% for low quality control (QC) standards and 95 to 105% for medium and high QC standards. Precision was <2% at all QC levels. The method was found to be accurate, precise, selective, and linear for L-T(4) over the analytical range. The HPLC method was successfully applied to the analysis of dissolution samples of marketed levothyroxine sodium tablets. Published by Elsevier B.V.

Development and application of a validated HPLC method for the analysis of dissolution samples of levothyroxine sodium drug products

PubMed Central

Collier, J.W.; Shah, R.B.; Bryant, A.R.; Habib, M.J.; Khan, M.A.; Faustino, P.J.

2011-01-01

A rapid, selective, and sensitive gradient HPLC method was developed for the analysis of dissolution samples of levothyroxine sodium tablets. Current USP methodology for levothyroxine (l-T4) was not adequate to resolve co-elutants from a variety of levothyroxine drug product formulations. The USP method for analyzing dissolution samples of the drug product has shown significant intra- and inter-day variability. The sources of method variability include chromatographic interferences introduced by the dissolution media and the formulation excipients. In the present work, chromatographic separation of levothyroxine was achieved on an Agilent 1100 Series HPLC with a Waters Nova-pak column (250mm × 3.9mm) using a 0.01 M phosphate buffer (pH 3.0)–methanol (55:45, v/v) in a gradient elution mobile phase at a flow rate of 1.0 mL/min and detection UV wavelength of 225 nm. The injection volume was 800 µL and the column temperature was maintained at 28 °C. The method was validated according to USP Category I requirements. The validation characteristics included accuracy, precision, specificity, linearity, and analytical range. The standard curve was found to have a linear relationship (r2 > 0.99) over the analytical range of 0.08–0.8 µg/mL. Accuracy ranged from 90 to 110% for low quality control (QC) standards and 95 to 105% for medium and high QC standards. Precision was <2% at all QC levels. The method was found to be accurate, precise, selective, and linear for l-T4 over the analytical range. The HPLC method was successfully applied to the analysis of dissolution samples of marketed levothyroxine sodium tablets. PMID:20947276

Methodological requirements for valid tissue-based biomarker studies that can be used in clinical practice.

PubMed

True, Lawrence D

2014-03-01

Paralleling the growth of ever more cost efficient methods to sequence the whole genome in minute fragments of tissue has been the identification of increasingly numerous molecular abnormalities in cancers--mutations, amplifications, insertions and deletions of genes, and patterns of differential gene expression, i.e., overexpression of growth factors and underexpression of tumor suppressor genes. These abnormalities can be translated into assays to be used in clinical decision making. In general terms, the result of such an assay is subject to a large number of variables regarding the characteristics of the available sample, particularities of the used assay, and the interpretation of the results. This review discusses the effects of these variables on assays of tissue-based biomarkers, classified by macromolecule--DNA, RNA (including micro RNA, messenger RNA, long noncoding RNA, protein, and phosphoprotein). Since the majority of clinically applicable biomarkers are immunohistochemically detectable proteins this review focuses on protein biomarkers. However, the principles outlined are mostly applicable to any other analyte. A variety of preanalytical variables impacts on the results obtained, including analyte stability (which is different for different analytes, i.e., DNA, RNA, or protein), period of warm and of cold ischemia, fixation time, tissue processing, sample storage time, and storage conditions. In addition, assay variables play an important role, including reagent specificity (notably but not uniquely an issue concerning antibodies used in immunohistochemistry), technical components of the assay, quantitation, and assay interpretation. Finally, appropriateness of an assay for clinical application is an important issue. Reference is made to publicly available guidelines to improve on biomarker development in general and requirements for clinical use in particular. Strategic goals are formulated in order to improve on the quality of biomarker reporting, including issues of analyte quality, experimental detail, assay efficiency and precision, and assay appropriateness.

A joint econometric analysis of seat belt use and crash-related injury severity.

PubMed

Eluru, Naveen; Bhat, Chandra R

2007-09-01

This paper formulates a comprehensive econometric structure that recognizes two important issues in crash-related injury severity analysis. First, the impact of a factor on injury severity may be moderated by various observed and unobserved variables specific to an individual or to a crash. Second, seat belt use is likely to be endogenous to injury severity. That is, it is possible that intrinsically unsafe drivers do not wear seat belts and are the ones likely to be involved in high injury severity crashes because of their unsafe driving habits. The preceding issues are considered in the current research effort through the development of a comprehensive model of seat belt use and injury severity that takes the form of a joint correlated random coefficients binary-ordered response system. To our knowledge, this is the first instance of such a model formulation and application not only in the safety analysis literature, but in the econometrics literature in general. The empirical analysis is based on the 2003 General Estimates System (GES) data base. Several types of variables are considered to explain seat belt use and injury severity levels, including driver characteristics, vehicle characteristics, roadway design attributes, environmental factors, and crash characteristics. The results, in addition to confirming the effects of various explanatory variables, also highlight the importance of (a) considering the moderating effects of unobserved individual/crash-related factors on the determinants of injury severity and (b) seat belt use endogeneity. From a policy standpoint, the results suggest that seat belt non-users, when apprehended in the act, should perhaps be subjected to both a fine (to increase the chances that they wear seat belts) as well as mandatory enrollment in a defensive driving course (to attempt to change their aggressive driving behaviors).

GFDL's ESM2 global coupled climate-carbon Earth System Models. Part I: physical formulation and baseline simulation characteristics

USGS Publications Warehouse

Dunne, John P.; John, Jasmin G.; Adcroft, Alistair J.; Griffies, Stephen M.; Hallberg, Robert W.; Shevalikova, Elena; Stouffer, Ronald J.; Cooke, William; Dunne, Krista A.; Harrison, Matthew J.; Krasting, John P.; Malyshev, Sergey L.; Milly, P.C.D.; Phillipps, Peter J.; Sentman, Lori A.; Samuels, Bonita L.; Spelman, Michael J.; Winton, Michael; Wittenberg, Andrew T.; Zadeh, Niki

2012-01-01

We describe the physical climate formulation and simulation characteristics of two new global coupled carbon-climate Earth System Models, ESM2M and ESM2G. These models demonstrate similar climate fidelity as the Geophysical Fluid Dynamics Laboratory's previous CM2.1 climate model while incorporating explicit and consistent carbon dynamics. The two models differ exclusively in the physical ocean component; ESM2M uses Modular Ocean Model version 4.1 with vertical pressure layers while ESM2G uses Generalized Ocean Layer Dynamics with a bulk mixed layer and interior isopycnal layers. Differences in the ocean mean state include the thermocline depth being relatively deep in ESM2M and relatively shallow in ESM2G compared to observations. The crucial role of ocean dynamics on climate variability is highlighted in the El Niño-Southern Oscillation being overly strong in ESM2M and overly weak ESM2G relative to observations. Thus, while ESM2G might better represent climate changes relating to: total heat content variability given its lack of long term drift, gyre circulation and ventilation in the North Pacific, tropical Atlantic and Indian Oceans, and depth structure in the overturning and abyssal flows, ESM2M might better represent climate changes relating to: surface circulation given its superior surface temperature, salinity and height patterns, tropical Pacific circulation and variability, and Southern Ocean dynamics. Our overall assessment is that neither model is fundamentally superior to the other, and that both models achieve sufficient fidelity to allow meaningful climate and earth system modeling applications. This affords us the ability to assess the role of ocean configuration on earth system interactions in the context of two state-of-the-art coupled carbon-climate models.

Unified Static and Dynamic Recrystallization Model for the Minerals of Earth's Mantle Using Internal State Variable Model

NASA Astrophysics Data System (ADS)

Cho, H. E.; Horstemeyer, M. F.; Baumgardner, J. R.

2017-12-01

In this study, we present an internal state variable (ISV) constitutive model developed to model static and dynamic recrystallization and grain size progression in a unified manner. This method accurately captures temperature, pressure and strain rate effect on the recrystallization and grain size. Because this ISV approach treats dislocation density, volume fraction of recrystallization and grain size as internal variables, this model can simultaneously track their history during the deformation with unprecedented realism. Based on this deformation history, this method can capture realistic mechanical properties such as stress-strain behavior in the relationship of microstructure-mechanical property. Also, both the transient grain size during the deformation and the steady-state grain size of dynamic recrystallization can be predicted from the history variable of recrystallization volume fraction. Furthermore, because this model has a capability to simultaneously handle plasticity and creep behaviors (unified creep-plasticity), the mechanisms (static recovery (or diffusion creep), dynamic recovery (or dislocation creep) and hardening) related to dislocation dynamics can also be captured. To model these comprehensive mechanical behaviors, the mathematical formulation of this model includes elasticity to evaluate yield stress, work hardening in treating plasticity, creep, as well as the unified recrystallization and grain size progression. Because pressure sensitivity is especially important for the mantle minerals, we developed a yield function combining Drucker-Prager shear failure and von Mises yield surfaces to model the pressure dependent yield stress, while using pressure dependent work hardening and creep terms. Using these formulations, we calibrated against experimental data of the minerals acquired from the literature. Additionally, we also calibrated experimental data for metals to show the general applicability of our model. Understanding of realistic mantle dynamics can only be acquired once the various deformation regimes and mechanisms are comprehensively modeled. The results of this study demonstrate that this ISV model is a good modeling candidate to help reveal the realistic dynamics of the Earth's mantle.

Shared written case formulations and weight change in outpatient therapy for anorexia nervosa: a naturalistic single case series.

PubMed

Gladwin, Alice M; Evangeli, Michael

2013-01-01

The therapeutic effects of written shared case formulations are underexplored and have not been examined in anorexia nervosa. This study explored the relationship between (a) the delivery (b) the quality of a shared written case formulation and weight in outpatient psychological therapy for anorexia nervosa. A naturalistic single case series approach was used to examine the case notes of women who had attended a specialist eating disorders service over a 2-year period. The case notes of 15 adult women who had undergone outpatient psychological therapy for anorexia nervosa with a shared written case formulation component were reviewed. The impact of the quality of the case formulation on weekly weight was examined for 14 of the clients where the case formulation was available. The nature of the relationship between the delivery of the written shared case formulation and weight was examined for all 15 clients. There was some evidence to support an association between delivery of the shared written case formulation and weight changes (both weight gain [five out of 15 clients] and weight loss [three out of 15 clients]) in individual cases. Higher case formulation quality was related to cases where weight change did not occur. The delivery of case formulations can be associated with important therapeutic change (both beneficial and potentially harmful) in anorexia nervosa. Future research into the causal mechanisms associated with sharing formulations will face the challenge of adopting strategies that allow for an in-depth exploration of complex therapy variables whilst overcoming methodological challenges. Copyright © 2012 John Wiley & Sons, Ltd.

An evolving effective stress approach to anisotropic distortional hardening

DOE PAGES

Lester, B. T.; Scherzinger, W. M.

2018-03-11

A new yield surface with an evolving effective stress definition is proposed for consistently and efficiently describing anisotropic distortional hardening. Specifically, a new internal state variable is introduced to capture the thermodynamic evolution between different effective stress definitions. The corresponding yield surface and evolution equations of the internal variables are derived from thermodynamic considerations enabling satisfaction of the second law. A closest point projection return mapping algorithm for the proposed model is formulated and implemented for use in finite element analyses. Finally, select constitutive and larger scale boundary value problems are solved to explore the capabilities of the model andmore » examine the impact of distortional hardening on constitutive and structural responses. Importantly, these simulations demonstrate the tractability of the proposed formulation in investigating large-scale problems of interest.« less

An evolving effective stress approach to anisotropic distortional hardening

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lester, B. T.; Scherzinger, W. M.

A new yield surface with an evolving effective stress definition is proposed for consistently and efficiently describing anisotropic distortional hardening. Specifically, a new internal state variable is introduced to capture the thermodynamic evolution between different effective stress definitions. The corresponding yield surface and evolution equations of the internal variables are derived from thermodynamic considerations enabling satisfaction of the second law. A closest point projection return mapping algorithm for the proposed model is formulated and implemented for use in finite element analyses. Finally, select constitutive and larger scale boundary value problems are solved to explore the capabilities of the model andmore » examine the impact of distortional hardening on constitutive and structural responses. Importantly, these simulations demonstrate the tractability of the proposed formulation in investigating large-scale problems of interest.« less

Three-variable solution in the (2+1)-dimensional null-surface formulation

NASA Astrophysics Data System (ADS)

Harriott, Tina A.; Williams, J. G.

2018-04-01

The null-surface formulation of general relativity (NSF) describes gravity by using families of null surfaces instead of a spacetime metric. Despite the fact that the NSF is (to within a conformal factor) equivalent to general relativity, the equations of the NSF are exceptionally difficult to solve, even in 2+1 dimensions. The present paper gives the first exact (2+1)-dimensional solution that depends nontrivially upon all three of the NSF's intrinsic spacetime variables. The metric derived from this solution is shown to represent a spacetime whose source is a massless scalar field that satisfies the general relativistic wave equation and the Einstein equations with minimal coupling. The spacetime is identified as one of a family of (2+1)-dimensional general relativistic spacetimes discovered by Cavaglià.

Risk based approach for design and optimization of stomach specific delivery of rifampicin.

PubMed

Vora, Chintan; Patadia, Riddhish; Mittal, Karan; Mashru, Rajashree

2013-10-15

The research envisaged focuses on risk management approach for better recognizing the risks, ways to mitigate them and propose a control strategy for the development of rifampicin gastroretentive tablets. Risk assessment using failure mode and effects analysis (FMEA) was done to depict the effects of specific failure modes related to respective formulation/process variable. A Box-Behnken design was used to investigate the effect of amount of sodium bicarbonate (X1), pore former HPMC (X2) and glyceryl behenate (X3) on percent drug release at 1st hour (Q1), 4th hour (Q4), 8th hour (Q8) and floating lag time (min). Main effects and interaction plots were generated to study effects of variables. Selection of the optimized formulation was done using desirability function and overlay contour plots. The optimized formulation exhibited Q1 of 20.9%, Q4 of 59.1%, Q8 of 94.8% and floating lag time of 4.0 min. Akaike information criteria and Model selection criteria revealed that the model was best described by Korsmeyer-Peppas power law. The residual plots demonstrated no existence of non-normality, skewness or outliers. The composite desirability for optimized formulation computed using equations and software were 0.84 and 0.86 respectively. FTIR, DSC and PXRD studies ruled out drug polymer interaction due to thermal treatment. Copyright © 2013 Elsevier B.V. All rights reserved.

Bioavailability enhancement of baclofen by gastroretentive floating formulation: statistical optimization, in vitro and in vivo pharmacokinetic studies.

PubMed

Thakar, Krishna; Joshi, Garima; Sawant, Krutika K

2013-06-01

The study was aimed to improve bioavailability of baclofen by developing gastroretentive floating drug delivery system (GFDDS). Preliminary optimization was done to select various release retardants to obtain minimum floating lag time, maximum floating duration and sustained release. Optimization by 3(2) factorial design was done using Polyox WSR 303 (X1) and HPMC K4M (X2) as independent variables and cumulative percentage drug released at 6 h (Q6h) as dependent variable. Optimized formulation showed floating lag time of 4-5 s, floated for more than 12 h and released the drug in sustained manner. In vitro release followed zero ordered kinetics and when fitted to Korsemeyer Peppas model, indicated drug release by combination of diffusion as well as chain relaxation. In vivo floatability study confirmed floatation for more than 6 h. In vivo pharmacokinetic studies in rabbits showed Cmax of 189.96 ± 13.04 ng/mL and Tmax of 4 ± 0.35 h for GFDDS. The difference for AUC(0-T) and AUC(0-∞) between the test and reference formulation was statistically significant (p > 0.05). AUC(0-T) and AUC(0-∞) for GFDDS was 2.34 and 2.43 times greater than the marketed formulation respectively. GFDDS provided prolonged gastric residence and showed significant increase in bioavailability of baclofen.

EPR and Bell's theorem: A critical review

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stapp, H.P.

1991-01-01

The argument of Einstein, Podolsky, and Rosen is reviewed with attention to logical structure and character of assumptions. Bohr's reply is discussed. Bell's contribution is formulated without use of hidden variables, and efforts to equate hidden variables to realism are critically examined. An alternative derivation of nonlocality that makes no use of hidden variables, microrealism, counterfactual definiteness, or any other assumption alien to orthodox quantum thinking is described in detail, with particular attention to the quartet or broken-square question.

Pectin-based oral drug delivery to the colon.

PubMed

Sande, Sverre Arne

2005-05-01

This review presents an overview of studies concerning oral formulations intended for site-specific drug delivery to the colon with pectin as the main excipient. The biological aspects covered include gastrointestinal transit and the enzymatic degradation of pectin. Scintigraphic methods demonstrating the functionality of pectin formulations are discussed. The main focus is on the various formulations reported, including matrix tablets, multiparticulate formulations as pellets and hydrogel beads, and pectin-based coatings. Also included is an evaluation of common excipients employed to improve colon specificity by crosslinking or increasing the hydrophobicity. Finally, properties of the pectin molecules that are important for successful formulations are examined. The conclusion is that the studies found in the literature provide an excellent platform for the development of pectin-based colon delivery systems.

A Priori Subgrid Analysis of Temporal Mixing Layers with Evaporating Droplets

NASA Technical Reports Server (NTRS)

Okongo, Nora; Bellan, Josette

1999-01-01

Subgrid analysis of a transitional temporal mixing layer with evaporating droplets has been performed using three sets of results from a Direct Numerical Simulation (DNS) database, with Reynolds numbers (based on initial vorticity thickness) as large as 600 and with droplet mass loadings as large as 0.5. In the DNS, the gas phase is computed using a Eulerian formulation, with Lagrangian droplet tracking. The Large Eddy Simulation (LES) equations corresponding to the DNS are first derived, and key assumptions in deriving them are first confirmed by computing the terms using the DNS database. Since LES of this flow requires the computation of unfiltered gas-phase variables at droplet locations from filtered gas-phase variables at the grid points, it is proposed to model these by assuming the gas-phase variables to be the sum of the filtered variables and a correction based on the filtered standard deviation; this correction is then computed from the Subgrid Scale (SGS) standard deviation. This model predicts the unfiltered variables at droplet locations considerably better than simply interpolating the filtered variables. Three methods are investigated for modeling the SGS standard deviation: the Smagorinsky approach, the Gradient model and the Scale-Similarity formulation. When the proportionality constant inherent in the SGS models is properly calculated, the Gradient and Scale-Similarity methods give results in excellent agreement with the DNS.

Design, Characterization, and Optimization of Controlled Drug Delivery System Containing Antibiotic Drug/s

PubMed Central

Shelate, Pragna; Dave, Divyang

2016-01-01

The objective of this work was design, characterization, and optimization of controlled drug delivery system containing antibiotic drug/s. Osmotic drug delivery system was chosen as controlled drug delivery system. The porous osmotic pump tablets were designed using Plackett-Burman and Box-Behnken factorial design to find out the best formulation. For screening of three categories of polymers, six independent variables were chosen for Plackett-Burman design. Osmotic agent sodium chloride and microcrystalline cellulose, pore forming agent sodium lauryl sulphate and sucrose, and coating agent ethyl cellulose and cellulose acetate were chosen as independent variables. Optimization of osmotic tablets was done by Box-Behnken design by selecting three independent variables. Osmotic agent sodium chloride, pore forming agent sodium lauryl sulphate, and coating agent cellulose acetate were chosen as independent variables. The result of Plackett-Burman and Box-Behnken design and ANOVA studies revealed that osmotic agent and pore former had significant effect on the drug release up to 12 hr. The observed independent variables were found to be very close to predicted values of most satisfactory formulation which demonstrates the feasibility of the optimization procedure in successful development of porous osmotic pump tablets containing antibiotic drug/s by using sodium chloride, sodium lauryl sulphate, and cellulose acetate as key excipients. PMID:27610247

Application of Box-Behnken design to prepare gentamicin-loaded calcium carbonate nanoparticles.

PubMed

Maleki Dizaj, Solmaz; Lotfipour, Farzaneh; Barzegar-Jalali, Mohammad; Zarrintan, Mohammad-Hossein; Adibkia, Khosro

2016-09-01

The aim of this research was to prepare and optimize calcium carbonate (CaCO3) nanoparticles as carriers for gentamicin sulfate. A chemical precipitation method was used to prepare the gentamicin sulfate-loaded CaCO3 nanoparticles. A 3-factor, 3-level Box-Behnken design was used for the optimization procedure, with the molar ratio of CaCl2: Na2CO3 (X1), the concentration of drug (X2), and the speed of homogenization (X3) as the independent variables. The particle size and entrapment efficiency were considered as response variables. Mathematical equations and response surface plots were used, along with the counter plots, to relate the dependent and independent variables. The results indicated that the speed of homogenization was the main variable contributing to particle size and entrapment efficiency. The combined effect of all three independent variables was also evaluated. Using the response optimization design, the optimized Xl-X3 levels were predicted. An optimized formulation was then prepared according to these levels, resulting in a particle size of 80.23 nm and an entrapment efficiency of 30.80%. It was concluded that the chemical precipitation technique, together with the Box-Behnken experimental design methodology, could be successfully used to optimize the formulation of drug-incorporated calcium carbonate nanoparticles.

Tulane/Xavier Vaccine Peptide Program

DTIC Science & Technology

2013-07-01

include a dry powder formulation, microemulsions , nonspherical liposomes, ceramic shell vesicles, and nanometer-sized silk particles. Nasal...pulmonary delivery: dry powder formulation, microemulsions , nonspherical liposomes, ceramic shell vesicles, and nanometer-sized silk particles. (3) Confirm...include a dry powder formulation, microemulsions , nonspherical liposomes, ceramic shell vesicles, and nanometer-sized silk particles. Nasal

Analysis of continuous-time switching networks

NASA Astrophysics Data System (ADS)

Edwards, R.

2000-11-01

Models of a number of biological systems, including gene regulation and neural networks, can be formulated as switching networks, in which the interactions between the variables depend strongly on thresholds. An idealized class of such networks in which the switching takes the form of Heaviside step functions but variables still change continuously in time has been proposed as a useful simplification to gain analytic insight. These networks, called here Glass networks after their originator, are simple enough mathematically to allow significant analysis without restricting the range of dynamics found in analogous smooth systems. A number of results have been obtained before, particularly regarding existence and stability of periodic orbits in such networks, but important cases were not considered. Here we present a coherent method of analysis that summarizes previous work and fills in some of the gaps as well as including some new results. Furthermore, we apply this analysis to a number of examples, including surprising long and complex limit cycles involving sequences of hundreds of threshold transitions. Finally, we show how the above methods can be extended to investigate aperiodic behaviour in specific networks, though a complete analysis will have to await new results in matrix theory and symbolic dynamics.

Variational formulation of hybrid problems for fully 3-D transonic flow with shocks in rotor

NASA Technical Reports Server (NTRS)

Liu, Gao-Lian

1991-01-01

Based on previous research, the unified variable domain variational theory of hybrid problems for rotor flow is extended to fully 3-D transonic rotor flow with shocks, unifying and generalizing the direct and inverse problems. Three variational principles (VP) families were established. All unknown boundaries and flow discontinuities (such as shocks, free trailing vortex sheets) are successfully handled via functional variations with variable domain, converting almost all boundary and interface conditions, including the Rankine Hugoniot shock relations, into natural ones. This theory provides a series of novel ways for blade design or modification and a rigorous theoretical basis for finite element applications and also constitutes an important part of the optimal design theory of rotor bladings. Numerical solutions to subsonic flow by finite elements with self-adapting nodes given in Refs., show good agreement with experimental results.

Design Methods and Optimization for Morphing Aircraft

NASA Technical Reports Server (NTRS)

Crossley, William A.

2005-01-01

This report provides a summary of accomplishments made during this research effort. The major accomplishments are in three areas. The first is the use of a multiobjective optimization strategy to help identify potential morphing features that uses an existing aircraft sizing code to predict the weight, size and performance of several fixed-geometry aircraft that are Pareto-optimal based upon on two competing aircraft performance objectives. The second area has been titled morphing as an independent variable and formulates the sizing of a morphing aircraft as an optimization problem in which the amount of geometric morphing for various aircraft parameters are included as design variables. This second effort consumed most of the overall effort on the project. The third area involved a more detailed sizing study of a commercial transport aircraft that would incorporate a morphing wing to possibly enable transatlantic point-to-point passenger service.

Notes on a Continuous-Variable Quantum Key Distribution Scheme

NASA Astrophysics Data System (ADS)

Ichikawa, Tsubasa; Hirano, Takuya; Matsubara, Takuto; Ono, Motoharu; Namiki, Ryo

2017-09-01

We develop a physical model to describe the signal transmission for a continuous-variable quantum key distribution scheme and investigate its security against a couple of eavesdropping attacks assuming that the eavesdropper's power is partly restricted owing to today's technological limitations. We consider an eavesdropper performing quantum optical homodyne measurement on the signal obtained by a type of beamsplitting attack. We also consider the case in which the eavesdropper Eve is unable to access a quantum memory and she performs heterodyne measurement on her signal without performing a delayed measurement. Our formulation includes a model in which the receiver's loss and noise are unaccessible by the eavesdropper. This setup enables us to investigate the condition that Eve uses a practical fiber differently from the usual beamsplitting attack where she can deploy a lossless transmission channel. The secret key rates are calculated in both the direct and reverse reconciliation scenarios.

Fem Formulation for Heat and Mass Transfer in Porous Medium

NASA Astrophysics Data System (ADS)

Azeem; Soudagar, Manzoor Elahi M.; Salman Ahmed, N. J.; Anjum Badruddin, Irfan

2017-08-01

Heat and mass transfer in porous medium can be modelled using three partial differential equations namely, momentum equation, energy equation and mass diffusion. These three equations are coupled to each other by some common terms that turn the whole phenomenon into a complex problem with inter-dependable variables. The current article describes the finite element formulation of heat and mass transfer in porous medium with respect to Cartesian coordinates. The problem under study is formulated into algebraic form of equations by using Galerkin's method with the help of two-node linear triangular element having three nodes. The domain is meshed with smaller sized elements near the wall region and bigger size away from walls.

Impact of formulation and process variables on solid-state stability of theophylline in controlled release formulations.

PubMed

Korang-Yeboah, Maxwell; Rahman, Ziyaur; Shah, Dhaval; Mohammad, Adil; Wu, Suyang; Siddiqui, Akhtar; Khan, Mansoor A

2016-02-29

Understanding the impact of pharmaceutical processing, formulation excipients and their interactions on the solid-state transitions of pharmaceutical solids during use and in storage is critical in ensuring consistent product performance. This study reports the effect of polymer viscosity, diluent type, granulation and granulating fluid (water and isopropanol) on the pseudopolymorphic transition of theophylline anhydrous (THA) in controlled release formulations as well as the implications of this transition on critical quality attributes of the tablets. Accordingly, 12 formulations were prepared using a full factorial screening design and monitored over a 3 month period at 40 °C and 75%. Physicochemical characterization revealed a drastic drop in tablet hardness accompanied by a very significant increase in moisture content and swelling of all formulations. Spectroscopic analysis (ssNMR, Raman, NIR and PXRD) indicated conversion of THA to theophylline monohydrate (TMO) in all formulations prepared by aqueous wet granulation in as early as two weeks. Although all freshly prepared formulations contained THA, the hydration-dehydration process induced during aqueous wet granulation hastened the pseudopolymorphic conversion of theophylline during storage through a cascade of events. On the other hand, no solid state transformation was observed in directly compressed formulations and formulations in which isopropanol was employed as a granulating fluid even after the twelve weeks study period. The transition of THA to TMO resulted in a decrease in dissolution while an increase in dissolution was observed in directly compressed and IPA granulated formulation. Consequently, the impact of pseudopolymorphic transition of theophylline on dissolution in controlled release formulations may be the net result of two opposing factors: swelling and softening of the tablets which tend to favor an increase in drug dissolution and hydration of theophylline which decreases the drug dissolution. Published by Elsevier B.V.

Forms of null Lagrangians in field theories of continuum mechanics

NASA Astrophysics Data System (ADS)

Kovalev, V. A.; Radaev, Yu. N.

2012-02-01

The divergence representation of a null Lagrangian that is regular in a star-shaped domain is used to obtain its general expression containing field gradients of order ≤ 1 in the case of spacetime of arbitrary dimension. It is shown that for a static three-component field in the three-dimensional space, a null Lagrangian can contain up to 15 independent elements in total. The general form of a null Lagrangian in the four-dimensional Minkowski spacetime is obtained (the number of physical field variables is assumed arbitrary). A complete theory of the null Lagrangian for the n-dimensional spacetime manifold (including the four-dimensional Minkowski spacetime as a special case) is given. Null Lagrangians are then used as a basis for solving an important variational problem of an integrating factor. This problem involves searching for factors that depend on the spacetime variables, field variables, and their gradients and, for a given system of partial differential equations, ensure the equality between the scalar product of a vector multiplier by the system vector and some divergence expression for arbitrary field variables and, hence, allow one to formulate a divergence conservation law on solutions to the system.

A respiratory alert model for the Shenandoah Valley, Virginia, USA

NASA Astrophysics Data System (ADS)

Hondula, David M.; Davis, Robert E.; Knight, David B.; Sitka, Luke J.; Enfield, Kyle; Gawtry, Stephen B.; Stenger, Phillip J.; Deaton, Michael L.; Normile, Caroline P.; Lee, Temple R.

2013-01-01

Respiratory morbidity (particularly COPD and asthma) can be influenced by short-term weather fluctuations that affect air quality and lung function. We developed a model to evaluate meteorological conditions associated with respiratory hospital admissions in the Shenandoah Valley of Virginia, USA. We generated ensembles of classification trees based on six years of respiratory-related hospital admissions (64,620 cases) and a suite of 83 potential environmental predictor variables. As our goal was to identify short-term weather linkages to high admission periods, the dependent variable was formulated as a binary classification of five-day moving average respiratory admission departures from the seasonal mean value. Accounting for seasonality removed the long-term apparent inverse relationship between temperature and admissions. We generated eight total models specific to the northern and southern portions of the valley for each season. All eight models demonstrate predictive skill (mean odds ratio = 3.635) when evaluated using a randomization procedure. The predictor variables selected by the ensembling algorithm vary across models, and both meteorological and air quality variables are included. In general, the models indicate complex linkages between respiratory health and environmental conditions that may be difficult to identify using more traditional approaches.

Abiotic Factors Affecting Benthic Invertebrate Biomass and Community Structure in a Fourth-Order Rocky Mountain Watershed

NASA Astrophysics Data System (ADS)

Chanat, J. G.; Clements, W. H.; MacDonald, L. H.

2005-05-01

The potential ecological impact of excess streambed sediment resulting from forest management activities is a persistent concern for land managers. This study examined the relationship between streambed sediment, along with other site- and reach-scale abiotic factors, and benthic macroinvertebrate community structure in a 272 km2 basin in the Colorado Front Range. Physical habitat parameters and invertebrates were sampled in late summer at 68 sites located in sixteen stream reaches. Invertebrate data were used to formulate twenty indices of community structure. Multiple regression identified site-level substrate particle size as the most important predictor of six indices, including total density (R2 = 0.22), biomass (R2 = 0.17), and taxa richness (R2 = 0.32). All of the remaining fourteen indices were most strongly predicted by reach-level variables, including discharge (percent shredders, R2 = 0.24; Plecoptera density, R2 = 0.29), and elevation (percent collector-filterers, R2 = 0.28; Trichoptera density, R2 = 0.37). Although the sites represented a wide range of substrate composition and embeddedness, no physical variable associated with fine sediment appeared as a strong predictor of any of the twenty indices. Thus, sediment is not among the most important factors associated with site-to-site variability of benthic community structure in this relatively pristine watershed.

Determining the Ocean's Role on the Variable Gravity Field and Earth Rotation

NASA Technical Reports Server (NTRS)

Ponte, Rui M.

2000-01-01

Our three year investigation, carried out over the period 18-19 Nov 2000, focused on the study of the variability in ocean angular momentum and mass signals and their relation to the Earth's variable rotation and gravity field. This final report includes a summary description of our work and a list of related publications and presentations. One thrust of the investigation was to determine and interpret the changes in the ocean mass field, as they impact on the variable gravity field and Earth rotation. In this regard, the seasonal cycle in local vertically-integrated ocean mass was analyzed using two ocean models of different complexity: (1) the simple constant-density, coarse resolution model of Ponte; and (2) the fully stratified, eddy-resolving model of Semtner and Chervin. The dynamics and thermodynamics of the seasonal variability in ocean mass were examined in detail, as well as the methodologies to calculate those changes under different model formulations. Another thrust of the investigation was to examine signals in ocean angular momentum (OAM) in relation to Earth rotation changes. A number of efforts were undertaken in this regard. Sensitivity of the oceanic excitation to different assumptions about how the ocean is forced and how it dissipates its energy was explored.

Freeze-drying of tert-butyl alcohol/water cosolvent systems: effects of formulation and process variables on residual solvents.

PubMed

Wittaya-Areekul, S; Nail, S L

1998-04-01

The objective of this study was to identify significant formulation and processing variables affecting levels of tert-butyl alcohol (TBA) and isopropyl alcohol (IPA) in freeze-dried solids prepared from TBA/water cosolvent systems. The variables examined were the physical state of the solute (crystalline vs amorphous), initial TBA concentration, freezing rate, cake thickness, and the temperature and duration of secondary drying. Sucrose and glycine were used as models for noncrystallizing and crystallizing solutes, respectively. The TBA concentration above which eutectic crystallization takes place was determined by differential scanning calorimetry. Model formulations were subjected to extremes of freezing rate by either dipping in liquid nitrogen or by slowly freezing on the shelf of a freeze-dryer. Dynamics of solvent loss during secondary drying was determined by withdrawing samples as a function of time at different shelf temperatures using a thief system. On the basis of these studies, the most important determinant of residual TBA level is the physical state of the solute. Freeze-dried glycine contained very low levels of residual TBA (0.01-0.03%) regardless of freezing rate or initial TBA concentration. For freeze-dried sucrose, residual TBA levels were approximately 2 orders of magnitude higher and were significantly affected by initial TBA concentration and freezing rate. For the sucrose/TBA/water system, relatively low residual TBA levels were obtained when the initial TBA level was above the threshold concentration for eutectic crystallization of TBA, whereas samples freeze-dried from solutions containing TBA concentrations below this threshold contained significantly higher levels of TBA. Residual IPA levels increased continuously with initial concentration of TBA in the sucrose/TBA/water system. Formulations of sucrose/TBA/water which were frozen rapidly contained residual TBA levels which were approximately twice those measured in the same formulation after slow freezing and drying under the same conditions. For the sucrose/TBA/water system, the temperature and time of secondary drying had only minimal influence on residual TBA in the freeze-dried solid. At low initial TBA concentrations (2%), residual TBA increases with increased cake thickness, perhaps because of the influence of depth of fill on effective freezing rate.

Decontamination formulations for disinfection and sterilization

DOEpatents

Tucker, Mark D.; Engler, Daniel E.

2007-09-18

Aqueous decontamination formulations that neutralize biological pathogens for disinfection and sterilization applications. Examples of suitable applications include disinfection of food processing equipment, disinfection of areas containing livestock, mold remediation, sterilization of medical instruments and direct disinfection of food surfaces, such as beef carcasses. The formulations include at least one reactive compound, bleaching activator, inorganic base, and water. The formulations can be packaged as a two-part kit system, and can have a pH value in the range of 7-8.

An Analysis on the Unemployment Rate in the Philippines: A Time Series Data Approach

NASA Astrophysics Data System (ADS)

Urrutia, J. D.; Tampis, R. L.; E Atienza, JB

2017-03-01

This study aims to formulate a mathematical model for forecasting and estimating unemployment rate in the Philippines. Also, factors which can predict the unemployment is to be determined among the considered variables namely Labor Force Rate, Population, Inflation Rate, Gross Domestic Product, and Gross National Income. Granger-causal relationship and integration among the dependent and independent variables are also examined using Pairwise Granger-causality test and Johansen Cointegration Test. The data used were acquired from the Philippine Statistics Authority, National Statistics Office, and Bangko Sentral ng Pilipinas. Following the Box-Jenkins method, the formulated model for forecasting the unemployment rate is SARIMA (6, 1, 5) × (0, 1, 1)4 with a coefficient of determination of 0.79. The actual values are 99 percent identical to the predicted values obtained through the model, and are 72 percent closely relative to the forecasted ones. According to the results of the regression analysis, Labor Force Rate and Population are the significant factors of unemployment rate. Among the independent variables, Population, GDP, and GNI showed to have a granger-causal relationship with unemployment. It is also found that there are at least four cointegrating relations between the dependent and independent variables.

JPL Innovation Foundry

NASA Technical Reports Server (NTRS)

Sherwood, Brent; McCleese, Daniel J.

2012-01-01

NASA supports the community of mission principal investigators by helping them ideate, mature, and propose concepts for new missions. As NASA's Federally Funded Research and Development Center (FFRDC), JPL is a primary resource for providing this service. The environmental context for the formulation lifecycle evolves continuously. Contemporary trends include: more competitors; more-complex mission ideas; scarcer formulation resources; and higher standards for technical evaluation. Derived requirements for formulation support include: stable, clear, reliable methods tailored for each stage of the formulation lifecycle; on-demand access to standout technical and programmatic subject-matter experts; optimized, outfitted facilities; smart access to learning embodied in a vast oeuvre of prior formulation work; hands-on method coaching. JPL has retooled its provision of integrated formulation lifecycle support to PIs, teams, and program offices in response to this need. This mission formulation enterprise is the JPL Innovation Foundry.

Statistical optimization of tretinoin-loaded penetration-enhancer vesicles (PEV) for topical delivery.

PubMed

Bavarsad, Neda; Akhgari, Abbas; Seifmanesh, Somayeh; Salimi, Anayatollah; Rezaie, Annahita

2016-02-29

The aim of this study was to develop and optimize deformable liposome for topical delivery of tretinoin. Liposomal formulations were designed based on the full factorial design and prepared by fusion method. The influence of different ratio of soy phosphatidylcholine and transcutol (independent variables) on incorporation efficiency and drug release in 15 min and 24 h (responses) from liposomal formulations was evaluated. Liposomes were characterized for their vesicle size and Differential Scanning Calorimetry (DSC) was used to investigate changes in their thermal behavior. The penetration and retention of drug was determined using mouse skin. Also skin histology study was performed. Particle size of all formulations was smaller than 20 nm. Incorporation efficiency of liposomes was 79-93 %. Formulation F7 (25:5) showed maximum drug release. Optimum formulations were selected based on the contour plots resulted by statistical equations of drug release in 15 min and 24 h. Solubility properties of transcutol led to higher skin penetration for optimum formulations compared to tretinoin cream. There was no significant difference between the amount of drug retained in the skin by applying optimum formulations and cream. Histopatological investigation suggested optimum formulations could decrease the adverse effect of tretinoin in liposome compared to conventional cream. According to the results of the study, it is concluded that deformable liposome containing transcutol may be successfully used for dermal delivery of tretinoin.

Effect of formulation variables on the physical properties and stability of Dead Sea mud masks.

PubMed

Shahin, Sawsan; Hamed, Saja; Alkhatib, Hatim S

2015-01-01

The physical stability of Dead Sea mud mask formulations under different conditions and their rheological properties were evaluated as a function of the type and level of thickeners, level of the humectant, incorporation of ethanol, and mode of mud treatment. Formulations were evaluated in terms of visual appearance, pH, moisture content, spreadability, extrudability, separation, rate of drying at 32 degrees C, and rheological properties. Prepared mud formulations and over-the-shelf products showed viscoplastic shear thinning behavior; satisfactory rheological behavior was observed with formulations containing a total concentration of thickeners less than 10% (w/w). Casson and Herschel-Bulkley models were found the most suitable to describe the rheological data of the prepared formulations. Thickener incorporation decreased phase separation and improved formulation stability. Bentonite incorporation in the mud prevented color changes during stability studies while glycerin improved spreadability. Addition of 5% (w/w) ethanol improved mud extrudability, slightly increased percent separation, accelerated drying at 32 degrees C, and decreased viscosity and yield stress values. Different mud treatment techniques did not cause a clear behavioral change in the final mud preparation. B10G and K5B5G were labeled as "best formulas" based on having satisfactory physical and aesthetic criteria investigated in this study, while other formulations failed in one or more of the tests we have performed.

Low within- and between-day variability in exposure to new insulin glargine 300 U/ml.

PubMed

Becker, R H A; Nowotny, I; Teichert, L; Bergmann, K; Kapitza, C

2015-03-01

To characterize the variability in exposure and metabolic effect of insulin glargine 300 U/ml (Gla-300) at steady state in people with type 1 diabetes (T1DM). A total of 50 participants with T1DM underwent two 24-h euglycaemic clamps in steady-state conditions after six once-daily administrations of 0.4 U/kg Gla-300 in a double-blind, randomized, two-treatment, two-period, crossover clamp study. Participants were randomized to receive Gla-300 as a standard cartridge formulation in the first treatment period, and as a formulation with enhanced stability through polysorbate-20 addition in the second treatment period, or vice versa. This design allowed the assessment of bioequivalence between formulations and, subsequently, within- and between-day variability. The cumulative exposure and effect of Gla-300 developed linearly over 24 h, and were evenly distributed across 6- and 12-h intervals. Diurnal fluctuation in exposure (within-day variability) was low; the peak-to-trough ratio of insulin concentration profiles was <2, and both the swing and peak-to-trough fluctuation were <1. Day-to-day reproducibility of exposure was high: the between-day within-subject coefficients of variation for total systemic exposure (area under the serum insulin glargine concentration time curve from time 0 to 24 h after dosing) and maximum insulin concentration were 17.4% [95% confidence interval (CI) 15-21] and 33.4% (95% CI 28-41), respectively. Reproducibility of the metabolic effect was lower than that of exposure. Gla-300 provides predictable, evenly distributed 24-h coverage as a result of low fluctuation and high reproducibility in insulin exposure, and appears suitable for effective basal insulin use. © 2014 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Effects of Formulation Variables on the Particle Size and Drug Encapsulation of Imatinib-Loaded Solid Lipid Nanoparticles.

PubMed

Gupta, Biki; Poudel, Bijay Kumar; Pathak, Shiva; Tak, Jin Wook; Lee, Hee Hyun; Jeong, Jee-Heon; Choi, Han-Gon; Yong, Chul Soon; Kim, Jong Oh

2016-06-01

Imatinib (IMT), an anticancer agent, inhibits receptor tyrosine kinases and is characterized by poor aqueous solubility, extensive first-pass metabolism, and rapid clearance. The aims of the current study are to prepare imatinib-loaded solid lipid nanoparticles (IMT-SLN) and study the effects of associated formulation variables on particle size and drug encapsulation on IMT-SLN using an experimental design. IMT-SLN was optimized by use of a "combo" approach involving Plackett-Burman design (PBD) and Box-Behnken design (BBD). PBD screening resulted in the determination of organic-to-aqueous phase ratio (O/A), drug-to-lipid ratio (D/L), and amount of Tween® 20 (Tw20) as three significant variables for particle size (S z), drug loading (DL), and encapsulation efficiency (EE) of IMT-SLN, which were used for optimization by BBD, yielding an optimized criteria of O/A = 0.04, D/L = 0.03, and Tw20 = 2.50% w/v. The optimized IMT-SLN exhibited monodispersed particles with a size range of 69.0 ± 0.9 nm, ζ-potential of -24.2 ± 1.2 mV, and DL and EE of 2.9 ± 0.1 and 97.6 ± 0.1% w/w, respectively. Results of in vitro release study showed a sustained release pattern, presumably by diffusion and erosion, with a higher release rate at pH 5.0, compared to pH 7.4. In conclusion, use of the combo experimental design approach enabled clear understanding of the effects of various formulation variables on IMT-SLN and aided in the preparation of a system which exhibited desirable physicochemical and release characteristics.

Aerosolization Characteristics of Dry Powder Inhaler Formulations for the Excipient Enhanced Growth (EEG) Application: Effect of Spray Drying Process Conditions on Aerosol Performance

PubMed Central

Son, Yoen-Ju; Longest, P. Worth; Hindle, Michael

2013-01-01

The aim of this study was to develop a spray dried submicrometer powder formulation suitable for the excipient enhanced growth (EEG) application. Combination particles were prepared using the Buchi Nano spray dryer B-90. A number of spray drying and formulation variables were investigated with the aims of producing dry powder formulations that were readily dispersed upon aerosolization and maximizing the fraction of submicrometer particles. Albuterol sulfate, mannitol, L-leucine, and poloxamer 188 were selected as a model drug, hygroscopic excipient, dispersibility enhancer and surfactant, respectively. Formulations were assessed by scanning electron microscopy and aerosol performance following aerosolization using an Aerolizer® dry powder inhaler (DPI). In vitro drug deposition was studied using a realistic mouth-throat (MT) model. Based on the in vitro aerosolization results, the best performing submicrometer powder formulation consisted of albuterol sulfate, mannitol, L-leucine and poloxamer 188 in a ratio of 30:48:20:2, containing 0.5% solids in a water:ethanol (80:20% v/v) solution which was spray dried at 70 °C. The submicrometer particle fraction (FPF1μm/ED) of this final formulation was 28.3% with more than 80% of the capsule contents being emitted during aerosolization. This formulation also showed 4.1% MT deposition. The developed combination formulation delivered a powder aerosol developed for the EEG application with high dispersion efficiency and low MT deposition from a convenient DPI device platform. PMID:23313343

Finite element computation of compressible flows with the SUPG formulation

NASA Technical Reports Server (NTRS)

Le Beau, G. J.; Tezduyar, T. E.

1991-01-01

Finite element computation of compressible Euler equations is presented in the context of the streamline-upwind/Petrov-Galerkin (SUPG) formulation. The SUPG formulation, which is based on adding stabilizing terms to the Galerkin formulation, is further supplemented with a shock capturing operator which addresses the difficulty in maintaining a satisfactory solution near discontinuities in the solution field. The shock capturing operator, which has been derived from work done in entropy variables for a similar operator, is shown to lead to an appropriate level of additional stabilization near shocks, without resulting in excessive numerical diffusion. An implicit treatment of the impermeable wall boundary condition is also presented. This treatment of the no-penetration condition offers increased stability for large Courant numbers, and accelerated convergence of the computations for both implicit and explicit applications. Several examples are presented to demonstrate the ability of this method to solve the equations governing compressible fluid flow.

Aeroelastic modeling of rotor blades with spanwise variable elastic axis offset: Classic issues revisited and new formulations

NASA Technical Reports Server (NTRS)

Bielawa, Richard L.

1988-01-01

In response to a systematic methodology assessment program directed to the aeroelastic stability of hingeless helicopter rotor blades, improved basic aeroelastic reformulations and new formulations relating to structural sweep were achieved. Correlational results are presented showing the substantially improved performance of the G400 aeroelastic analysis incorporating these new formulations. The formulations pertain partly to sundry solutions to classic problem areas, relating to dynamic inflow with vortex-ring state operation and basic blade kinematics, but mostly to improved physical modeling of elastic axis offset (structural sweep) in the presence of nonlinear structural twist. Specific issues addressed are an alternate modeling of the delta EI torsional excitation due to compound bending using a force integration approach, and the detailed kinematic representation of an elastically deflected point mass of a beam with both structural sweep and nonlinear twist.

Comparison of two transonic noise prediction formulations using the aircraft noise prediction program

NASA Technical Reports Server (NTRS)

Spence, Peter L.

1987-01-01

This paper addresses recently completed work on using Farassat's Formulation 3 noise prediction code with the Aircraft Noise Prediction Program (ANOPP). Software was written to link aerodynamic loading generated by the Propeller Loading (PLD) module within ANOPP with formulation 3. Included are results of comparisons between Formulation 3 with ANOPP's existing noise prediction modules, Subsonic Propeller Noise (SPN) and Transonic Propeller Noise (TPN). Four case studies are investigated. Results of the comparison studies show excellent agreement for the subsonic cases. Differences found in the comparisons made under transonic conditions are strictly numerical and can be explained by the way in which the time derivative is calculated in Formulation 3. Also included is a section on how to execute Formulation 3 with ANOPP.

Superfield quantization

NASA Astrophysics Data System (ADS)

Batalin, I. A.; Bering, K.; Damgaard, P. H.

1998-03-01

We present a superfield formulation of the quantization program for theories with first-class constraints. An exact operator formulation is given, and we show how to set up a phase-space path integral entirely in terms of superfields. BRST transformations and canonical transformations enter on equal footing, and they allow us to establish a superspace analog of the BFV theorem. We also present a formal derivation of the Lagrangian superfield analogue of the field-antifield formalism by an integration over half of the phase-space variables.

Formulation and evaluation of floating matrix tablet of stavudine

PubMed Central

Prajapati, Pankaj H; Nakum, Vijay V; Patel, Chhagan N

2012-01-01

Background/Aim: The purpose of the study was to prolong the gastric residence time of stavudine by designing its floating tablets and to study the influence of different polymers on its release rate. Materials and Methods: The floating mix matrix tablets of stavudine were prepared by melt granulation method. Beeswax was used as hydrophobic meltable material. Hydroxypropyl methylcellulose (HPMC), sodium bicarbonate, and ethyl cellulose were used as matrixing agent, gas generating agent, and floating enhancer, respectively. The prepared tablets were evaluated for physicochemical parameters such as hardness, weight variation, friability, floating properties (floating lag time, total floating time), drug content, stability study, and in vitro drug release. The drug- polymer interaction was studied by Differential Scanning Calorimetry (DSC) thermal analysis and Fourier transform infared (FT-IR). Results: The floating lag time of all the formulations was within the prescribed limit (<3 min). All the formulations showed good matrix integrity and retarded the release of drug for 12 h except the formulation F5.The concentration of beeswax (X1), HPMC K4M (X2), and ethyl cellulose (X3) were selected as independent variables and drug release values at 1 (Q1), at 6 (Q6) and at 12 h (Q12) as dependent variables. Formulation F7 was selected as an optimum formulation as it showed more similarity in dissolution profile with theoretical profile (similarity factor, f2 = 70.91). The dissolution of batch F7 can be described by zero-order kinetics (R2 =0.9936) with anomalous (non-Fickian) diffusion as the release mechanism (n=0.545). There was no difference observed in release profile after temperature sensitivity study at 40°C/75% relative humidity (RH) for 1 month. Conclusion: It can be concluded from this study that the combined mix matrix system containing hydrophobic and hydrophilic polymer minimized the burst release of drug from the tablet and achieved a drug release by zero-order kinetics, which is practically difficult with only hydrophilic matrix. PMID:23119237

Efficient Reformulation of HOTFGM: Heat Conduction with Variable Thermal Conductivity

NASA Technical Reports Server (NTRS)

Zhong, Yi; Pindera, Marek-Jerzy; Arnold, Steven M. (Technical Monitor)

2002-01-01

Functionally graded materials (FGMs) have become one of the major research topics in the mechanics of materials community during the past fifteen years. FGMs are heterogeneous materials, characterized by spatially variable microstructure, and thus spatially variable macroscopic properties, introduced to enhance material or structural performance. The spatially variable material properties make FGMs challenging to analyze. The review of the various techniques employed to analyze the thermodynamical response of FGMs reveals two distinct and fundamentally different computational strategies, called uncoupled macromechanical and coupled micromechanical approaches by some investigators. The uncoupled macromechanical approaches ignore the effect of microstructural gradation by employing specific spatial variations of material properties, which are either assumed or obtained by local homogenization, thereby resulting in erroneous results under certain circumstances. In contrast, the coupled approaches explicitly account for the micro-macrostructural interaction, albeit at a significantly higher computational cost. The higher-order theory for functionally graded materials (HOTFGM) developed by Aboudi et al. is representative of the coupled approach. However, despite its demonstrated utility in applications where micro-macrostructural coupling effects are important, the theory's full potential is yet to be realized because the original formulation of HOTFGM is computationally intensive. This, in turn, limits the size of problems that can be solved due to the large number of equations required to mimic realistic material microstructures. Therefore, a basis for an efficient reformulation of HOTFGM, referred to as user-friendly formulation, is developed herein, and subsequently employed in the construction of the efficient reformulation using the local/global conductivity matrix approach. In order to extend HOTFGM's range of applicability, spatially variable thermal conductivity capability at the local level is incorporated into the efficient reformulation. Analytical solutions to validate both the user-friendly and efficient reformulations am also developed. Volume discretization sensitivity and validation studies, as well as a practical application of the developed efficient reformulation are subsequently carried out. The presented results illustrate the accuracy and implementability of both the user-friendly formulation and the efficient reformulation of HOTFGM.

Release of 5-Aminosalicylic Acid (5-ASA) from Mesalamine Formulations at Various pH Levels.

PubMed

Abinusawa, Adeyinka; Tenjarla, Srini

2015-05-01

Oral formulations of 5-aminosalicylic acid (5-ASA) for treatment of ulcerative colitis have been developed to minimize absorption prior to the drug reaching the colon. In this study, we investigate the release of 5-ASA from available oral mesalamine formulations in physiologically relevant pH conditions. Release of 5-ASA from 6 mesalamine formulations (APRISO®, Salix Pharmaceuticals, Inc., USA; ASACOL® MR, Procter & Gamble Pharmaceuticals UK Ltd.; ASACOL® HD, Procter & Gamble Pharmaceuticals, USA; MEZAVANT XL®, Shire US Inc.; PENTASA®, Ferring Pharmaceuticals, Ltd., UK; SALOFALK®, Dr. Falk Pharma UK Ltd.) was evaluated using United States Pharmacopeia apparatus I and II at pH values of 1.0 (2 h), 6.0 (1 h), and 6.8 (8 h). Dissolution profiles were determined for each formulation, respectively. Of the tested formulations, only the PENTASA formulation demonstrated release of 5-ASA at pH 1.0 (48%), with 56% cumulative release after exposure to pH 6.0 and 92% 5-ASA release after 6-8 h at pH 6.8. No other mesalamine formulation showed >1% drug release at pH 1.0. The APRISO formulation revealed 36% 5-ASA release at pH 6.0, with 100% release after 3 h at pH 6.8. The SALOFALK formulation revealed 11% 5-ASA release at pH 6.0, with 100% release after 1 h at pH 6.8. No 5-ASA was released by the ASACOL MR, ASACOL HD, and MEZAVANT XL formulations at pH 6.0. At pH 6.8, the ASACOL MR and ASACOL HD formulations exhibited complete release of 5-ASA after 4 and 2 h, respectively, and the MEZAVANT XL formulation demonstrated complete 5-ASA release over 6-7 h. 5-Aminosalicylic acid release profiles were variable among various commercially available formulations. Shire Development LLC.

A constitutive model for magnetostriction based on thermodynamic framework

NASA Astrophysics Data System (ADS)

Ho, Kwangsoo

2016-08-01

This work presents a general framework for the continuum-based formulation of dissipative materials with magneto-mechanical coupling in the viewpoint of irreversible thermodynamics. The thermodynamically consistent model developed for the magnetic hysteresis is extended to include the magnetostrictive effect. The dissipative and hysteretic response of magnetostrictive materials is captured through the introduction of internal state variables. The evolution rate of magnetostrictive strain as well as magnetization is derived from thermodynamic and dissipative potentials in accordance with the general principles of thermodynamics. It is then demonstrated that the constitutive model is competent to describe the magneto-mechanical behavior by comparing simulation results with the experimental data reported in the literature.

Stronger steerability criterion for more uncertain continuous-variable systems

NASA Astrophysics Data System (ADS)

Chowdhury, Priyanka; Pramanik, Tanumoy; Majumdar, A. S.

2015-10-01

We derive a fine-grained uncertainty relation for the measurement of two incompatible observables on a single quantum system of continuous variables, and show that continuous-variable systems are more uncertain than discrete-variable systems. Using the derived fine-grained uncertainty relation, we formulate a stronger steering criterion that is able to reveal the steerability of NOON states that has hitherto not been possible using other criteria. We further obtain a monogamy relation for our steering inequality which leads to an, in principle, improved lower bound on the secret key rate of a one-sided device independent quantum key distribution protocol for continuous variables.

Multi-point Adjoint-Based Design of Tilt-Rotors in a Noninertial Reference Frame

NASA Technical Reports Server (NTRS)

Jones, William T.; Nielsen, Eric J.; Lee-Rausch, Elizabeth M.; Acree, Cecil W.

2014-01-01

Optimization of tilt-rotor systems requires the consideration of performance at multiple design points. In the current study, an adjoint-based optimization of a tilt-rotor blade is considered. The optimization seeks to simultaneously maximize the rotorcraft figure of merit in hover and the propulsive efficiency in airplane-mode for a tilt-rotor system. The design is subject to minimum thrust constraints imposed at each design point. The rotor flowfields at each design point are cast as steady-state problems in a noninertial reference frame. Geometric design variables used in the study to control blade shape include: thickness, camber, twist, and taper represented by as many as 123 separate design variables. Performance weighting of each operational mode is considered in the formulation of the composite objective function, and a build up of increasing geometric degrees of freedom is used to isolate the impact of selected design variables. In all cases considered, the resulting designs successfully increase both the hover figure of merit and the airplane-mode propulsive efficiency for a rotor designed with classical techniques.

Modeling of Rolling Element Bearing Mechanics: Computer Program Updates

NASA Technical Reports Server (NTRS)

Ryan, S. G.

1997-01-01

The Rolling Element Bearing Analysis System (REBANS) extends the capability available with traditional quasi-static bearing analysis programs by including the effects of bearing race and support flexibility. This tool was developed under contract for NASA-MSFC. The initial version delivered at the close of the contract contained several errors and exhibited numerous convergence difficulties. The program has been modified in-house at MSFC to correct the errors and greatly improve the convergence. The modifications consist of significant changes in the problem formulation and nonlinear convergence procedures. The original approach utilized sequential convergence for nested loops to achieve final convergence. This approach proved to be seriously deficient in robustness. Convergence was more the exception than the rule. The approach was changed to iterate all variables simultaneously. This approach has the advantage of using knowledge of the effect of each variable on each other variable (via the system Jacobian) when determining the incremental changes. This method has proved to be quite robust in its convergence. This technical memorandum documents the changes required for the original Theoretical Manual and User's Manual due to the new approach.

Variables that affect the mechanism of drug release from osmotic pumps coated with acrylate/methacrylate copolymer latexes.

PubMed

Jensen, J L; Appel, L E; Clair, J H; Zentner, G M

1995-05-01

The feasibility of using modified Eudragit acrylic latexes as microporous coatings for osmotic devices was investigated. Potassium chloride tablets were coated with mixtures of Eudragit RS30D and RL30D acrylic latexes that also contained a plasticizer (triethyl citrate or acetyl tributyl citrate) and a pore-forming agent (urea). A 2(5-1) fractional factorial experimental design was employed to determine the effect of five formulation variables (RS30D:RL30D polymer ratio plasticizer type, plasticizer level, urea level, and cure) on the in vitro release rate of KCl in deionized water (di water), lag time, and coat burst strength. The RS30D:RL30D polymer ratio had the greatest effect on the release rate, and both lag time and burst strength were most affected by the urea level. Statistical optimization was performed, and a coat formulation with predicted desirable in vitro performance was prepared and tested. The in vitro release rate (di water), lag time, and coat burst strength agreed well with the prediction. Dissolutions were also performed in phosphate buffered saline (PBS; pH 7.4); several formulations released markedly slower in PBS than in di water. This discrepancy was dependent on the type of plasticizer and the amount of pore former. Only those coat formulations containing acetyl tributyl citrate as the plasticizer and a 100% urea [(g urea/g polymer solids) x 100] level exhibited similar release rates in di water and PBS. The mechanism of release from these devices was primarily osmotic, whereas the release from devices coated with a formulation containing triethyl citrate and 50% urea was not dependent on the osmotic pressure difference. Devices with an osmotic release mechanism behaved similarly in vivo and in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Production and storage stability of formulated chicken nuggets using konjac flour and shiitake mushrooms.

PubMed

Akesowan, Adisak

2016-10-01

Formulated chicken nuggets which are low in fat and, high in dietary fiber and free from phosphate were developed by adding various levels of a konjac flour/xanthan gum (KF/XG) (3:1) mixture (0.2-1.5 %, w/w) and shiitake powder (SP) (1-4 %, w/w). A central composite rotatable design was used to investigate the influence of variables on the physical and sensory properties of nuggets and to optimize the formulated nugget formulation. The addition of the KF/XG mixture and SP was effective in improving nugget firmness and increasing hedonic scores for color, taste, flavor and overall acceptability. The nugget became darker with more SP was added. Optimal nuggets with 0.39 % KF/XG mixture and 1.84 % SP had reduced fat, higher dietary fiber and amino acids. After frozen (-18 ± 2 °C) storage, optimal formulated nuggets showed slower decreased in moisture, hardness and chewiness compared to standard nuggets. Konjac flour and SP also lowered lipid oxidation in frozen formulated nuggets. A slight change in sensory score was observed in both nuggets were microbiologically safe after frozen storage for 75 days.

Consumer-Resource Dynamics: Quantity, Quality, and Allocation

PubMed Central

Getz, Wayne M.; Owen-Smith, Norman

2011-01-01

Background The dominant paradigm for modeling the complexities of interacting populations and food webs is a system of coupled ordinary differential equations in which the state of each species, population, or functional trophic group is represented by an aggregated numbers-density or biomass-density variable. Here, using the metaphysiological approach to model consumer-resource interactions, we formulate a two-state paradigm that represents each population or group in a food web in terms of both its quantity and quality. Methodology and Principal Findings The formulation includes an allocation function controlling the relative proportion of extracted resources to increasing quantity versus elevating quality. Since lower quality individuals senesce more rapidly than higher quality individuals, an optimal allocation proportion exists and we derive an expression for how this proportion depends on population parameters that determine the senescence rate, the per-capita mortality rate, and the effects of these rates on the dynamics of the quality variable. We demonstrate that oscillations do not arise in our model from quantity-quality interactions alone, but require consumer-resource interactions across trophic levels that can be stabilized through judicious resource allocation strategies. Analysis and simulations provide compelling arguments for the necessity of populations to evolve quality-related dynamics in the form of maternal effects, storage or other appropriate structures. They also indicate that resource allocation switching between investments in abundance versus quality provide a powerful mechanism for promoting the stability of consumer-resource interactions in seasonally forcing environments. Conclusions/Significance Our simulations show that physiological inefficiencies associated with this switching can be favored by selection due to the diminished exposure of inefficient consumers to strong oscillations associated with the well-known paradox of enrichment. Also our results demonstrate how allocation switching can explain observed growth patterns in experimental microbial cultures and discuss how our formulation can address questions that cannot be answered using the quantity-only paradigms that currently predominate. PMID:21283752

Impact of the emulsification-diffusion method on the development of pharmaceutical nanoparticles.

PubMed

Quintanar-Guerrero, David; Zambrano-Zaragoza, María de la Luz; Gutierrez-Cortez, Elsa; Mendoza-Munoz, Nestor

2012-12-01

Nanotechnology is having a profound impact in many scientific fields and it has become one of the most important and exciting discipline. Like all technological advances, nanotechnology has its own scientific basis with a broad interdisciplinary effect. Perhaps, we are witnessing an exponential growth of nanotechnology, reflection of this is the important increase in the number of patents, scientific papers and specialized "nano" meetings and journals. The impact in the pharmaceutical area is related to the use of colloidal drug delivery systems as carriers for bioactive agents, in particular, the nanoparticle technology. The term nanoparticles designates solid submicronic particles formed of acceptable materials (e.g. polymers, lipids, etc.) containing an active substance. It includes both nanospheres (matricial systems) and nanocapsules (membrane systems). The knowledge of the nanoparticle preparation methods is a key issue for the formulator involved with drug-delivery research and development. In general, the methods based on preformed polymers, in particular biodegradable polymers, are preferred due to their easy implementation and lower potential toxicity. One of the most widely used methods to prepare polymeric nanoparticles is emulsification-diffusion. This method has been discussed in some reviews that compile research works but has a small number of patents. In this review, the emulsification-diffusion method is discussed from a technological point of view in order to show the operating conditions and formulation variables from data extracted of recent patents and experimental works. The main idea is to provide the reader with a general guide for formulators to make decisions about the usefulness of this method to develop specific nanoparticulate systems. The first part of this review provides an overview of the emulsification-diffusion method to prepare polymeric nanoparticles, while the second part evaluates the influence of preparative variables on the properties of the obtained particles relating the events to the formation mechanism. Novel innovations and applications of the method have also been compiled.

Thermochemical nonequilibrium in atomic hydrogen at elevated temperatures

NASA Technical Reports Server (NTRS)

Scott, R. K.

1972-01-01

A numerical study of the nonequilibrium flow of atomic hydrogen in a cascade arc was performed to obtain insight into the physics of the hydrogen cascade arc. A rigorous mathematical model of the flow problem was formulated, incorporating the important nonequilibrium transport phenomena and atomic processes which occur in atomic hydrogen. Realistic boundary conditions, including consideration of the wall electrostatic sheath phenomenon, were included in the model. The governing equations of the asymptotic region of the cascade arc were obtained by writing conservation of mass and energy equations for the electron subgas, an energy conservation equation for heavy particles and an equation of state. Finite-difference operators for variable grid spacing were applied to the governing equations and the resulting system of strongly coupled, stiff equations were solved numerically by the Newton-Raphson method.

Flight Dynamics of Flexible Aircraft with Aeroelastic and Inertial Force Interactions

NASA Technical Reports Server (NTRS)

Nguyen, Nhan T.; Tuzcu, Ilhan

2009-01-01

This paper presents an integrated flight dynamic modeling method for flexible aircraft that captures coupled physics effects due to inertial forces, aeroelasticity, and propulsive forces that are normally present in flight. The present approach formulates the coupled flight dynamics using a structural dynamic modeling method that describes the elasticity of a flexible, twisted, swept wing using an equivalent beam-rod model. The structural dynamic model allows for three types of wing elastic motion: flapwise bending, chordwise bending, and torsion. Inertial force coupling with the wing elasticity is formulated to account for aircraft acceleration. The structural deflections create an effective aeroelastic angle of attack that affects the rigid-body motion of flexible aircraft. The aeroelastic effect contributes to aerodynamic damping forces that can influence aerodynamic stability. For wing-mounted engines, wing flexibility can cause the propulsive forces and moments to couple with the wing elastic motion. The integrated flight dynamics for a flexible aircraft are formulated by including generalized coordinate variables associated with the aeroelastic-propulsive forces and moments in the standard state-space form for six degree-of-freedom flight dynamics. A computational structural model for a generic transport aircraft has been created. The eigenvalue analysis is performed to compute aeroelastic frequencies and aerodynamic damping. The results will be used to construct an integrated flight dynamic model of a flexible generic transport aircraft.

Modelling drug degradation in a spray dried polymer dispersion using a modified Arrhenius equation.

PubMed

Patterson, Adele; Ferreira, Ana P; Banks, Elizabeth; Skeene, Kirsty; Clarke, Graham; Nicholson, Sarah; Rawlinson-Malone, Clare

2015-01-15

The Pharmaceutical industry is increasingly utilizing amorphous technologies to overcome solubility challenges. A common approach is the use of drug in polymer dispersions to prevent recrystallization of the amorphous drug. Understanding the factors affecting chemical and physical degradation of the drug within these complex systems, e.g., temperature and relative humidity, is an important step in the selection of a lead formulation, and development of appropriate packaging/storage control strategies. The Arrhenius equation has been used as the basis of a number of models to predict the chemical stability of formulated product. In this work, we investigate the increase in chemical degradation seen for one particular spray dried dispersion formulation using hydroxypropyl methylcellulose acetate succinate (HPMC-AS). Samples, prepared using polymers with different substitution levels, were placed on storage for 6 months under a range of different temperature and relative humidity conditions and the degradant level monitored using high-performance liquid chromatography (HPLC). While the data clearly illustrates the impact of temperature and relative humidity on the degradant levels detected, it also highlighted that these terms do not account for all the variability in the data. An extension of the Arrhenius equation to include a term for the polymer chemistry, specifically the degree of succinoyl substitution on the polymer backbone, was shown to improve the fit of the model to the data. Copyright © 2014 Elsevier B.V. All rights reserved.

Beyond Bernoulli

PubMed Central

Donati, Fabrizio; Myerson, Saul; Bissell, Malenka M.; Smith, Nicolas P.; Neubauer, Stefan; Monaghan, Mark J.; Nordsletten, David A.

2017-01-01

Background— Transvalvular peak pressure drops are routinely assessed noninvasively by echocardiography using the Bernoulli principle. However, the Bernoulli principle relies on several approximations that may not be appropriate, including that the majority of the pressure drop is because of the spatial acceleration of the blood flow, and the ejection jet is a single streamline (single peak velocity value). Methods and Results— We assessed the accuracy of the Bernoulli principle to estimate the peak pressure drop at the aortic valve using 3-dimensional cardiovascular magnetic resonance flow data in 32 subjects. Reference pressure drops were computed from the flow field, accounting for the principles of physics (ie, the Navier–Stokes equations). Analysis of the pressure components confirmed that the spatial acceleration of the blood jet through the valve is most significant (accounting for 99% of the total drop in stenotic subjects). However, the Bernoulli formulation demonstrated a consistent overestimation of the transvalvular pressure (average of 54%, range 5%–136%) resulting from the use of a single peak velocity value, which neglects the velocity distribution across the aortic valve plane. This assumption was a source of uncontrolled variability. Conclusions— The application of the Bernoulli formulation results in a clinically significant overestimation of peak pressure drops because of approximation of blood flow as a single streamline. A corrected formulation that accounts for the cross-sectional profile of the blood flow is proposed and adapted to both cardiovascular magnetic resonance and echocardiographic data. PMID:28093412

Optimization of Bread Enriched with Garcinia mangostana Pericarp Powder

NASA Astrophysics Data System (ADS)

Ibrahim, U. K.; Salleh, R. Mohd; Maqsood-ul-Hague, S. N. S.; Hashib, S. Abd; Karim, S. F. Abd

2018-05-01

The aim of present work is to optimize the formulation of bread enhanced with Garcinia mangostana pericarp powder with the combination of baking process conditions. The independent variables used were baking time (15 - 30 minutes), baking temperature (180 - 220°C) and pericarp powder concentration (0.5 - 2.0%). The physical and chemical properties of bread sample such as antioxidant activity, phenolic content, moisture analysis and colour parameters were studied. Bread dough without fortification of pericarp powder was used as control. Data obtained were analyzed by multiple regressions and the significant model such as linear and quadratic with variables interactions were used. As a conclusion, the optimum baking conditions were found at 213°C baking temperature with 23 minutes baking time and addition of 0.87% for Garcinia mangostana pericarp powder to the bread formulation.

Investigation of energy management strategies for photovoltaic systems - An analysis technique

NASA Technical Reports Server (NTRS)

Cull, R. C.; Eltimsahy, A. H.

1982-01-01

Progress is reported in formulating energy management strategies for stand-alone PV systems, developing an analytical tool that can be used to investigate these strategies, applying this tool to determine the proper control algorithms and control variables (controller inputs and outputs) for a range of applications, and quantifying the relative performance and economics when compared to systems that do not apply energy management. The analysis technique developed may be broadly applied to a variety of systems to determine the most appropriate energy management strategies, control variables and algorithms. The only inputs required are statistical distributions for stochastic energy inputs and outputs of the system and the system's device characteristics (efficiency and ratings). Although the formulation was originally driven by stand-alone PV system needs, the techniques are also applicable to hybrid and grid connected systems.

Investigation of energy management strategies for photovoltaic systems - An analysis technique

NASA Astrophysics Data System (ADS)

Cull, R. C.; Eltimsahy, A. H.

Progress is reported in formulating energy management strategies for stand-alone PV systems, developing an analytical tool that can be used to investigate these strategies, applying this tool to determine the proper control algorithms and control variables (controller inputs and outputs) for a range of applications, and quantifying the relative performance and economics when compared to systems that do not apply energy management. The analysis technique developed may be broadly applied to a variety of systems to determine the most appropriate energy management strategies, control variables and algorithms. The only inputs required are statistical distributions for stochastic energy inputs and outputs of the system and the system's device characteristics (efficiency and ratings). Although the formulation was originally driven by stand-alone PV system needs, the techniques are also applicable to hybrid and grid connected systems.

Creating a non-linear total sediment load formula using polynomial best subset regression model

NASA Astrophysics Data System (ADS)

Okcu, Davut; Pektas, Ali Osman; Uyumaz, Ali

2016-08-01

The aim of this study is to derive a new total sediment load formula which is more accurate and which has less application constraints than the well-known formulae of the literature. 5 most known stream power concept sediment formulae which are approved by ASCE are used for benchmarking on a wide range of datasets that includes both field and flume (lab) observations. The dimensionless parameters of these widely used formulae are used as inputs in a new regression approach. The new approach is called Polynomial Best subset regression (PBSR) analysis. The aim of the PBRS analysis is fitting and testing all possible combinations of the input variables and selecting the best subset. Whole the input variables with their second and third powers are included in the regression to test the possible relation between the explanatory variables and the dependent variable. While selecting the best subset a multistep approach is used that depends on significance values and also the multicollinearity degrees of inputs. The new formula is compared to others in a holdout dataset and detailed performance investigations are conducted for field and lab datasets within this holdout data. Different goodness of fit statistics are used as they represent different perspectives of the model accuracy. After the detailed comparisons are carried out we figured out the most accurate equation that is also applicable on both flume and river data. Especially, on field dataset the prediction performance of the proposed formula outperformed the benchmark formulations.

Similarity theory of the buoyantly interactive planetary boundary layer with entrainment

NASA Technical Reports Server (NTRS)

Hoffert, M. I.; Sud, Y. C.

1976-01-01

A similarity model is developed for the vertical profiles of turbulent flow variables in an entraining turbulent boundary layer of arbitrary buoyant stability. In the general formulation the vertical profiles, internal rotation of the velocity vector, discontinuities or jumps at a capping inversion and bulk aerodynamic coefficients of the boundary layer are given by solutions to a system of ordinary differential equations in the similarity variable. To close the system, a formulation for buoyantly interactive eddy diffusivity in the boundary layer is introduced which recovers Monin-Obukhov similarity near the surface and incorporates a hypothesis accounting for the observed variation of mixing length throughout the boundary layer. The model is tested in simplified versions which depend only on roughness, surface buoyancy, and Coriolis effects by comparison with planetary-boundary-layer wind- and temperature-profile observations, measurements of flat-plate boundary layers in a thermally stratified wind tunnel and observations of profiles of terms in the turbulent kinetic-energy budget of convective planetary boundary layers. On balance, the simplified model reproduced the trend of these various observations and experiments reasonably well, suggesting that the full similarity formulation be pursued further.

Predicting the Fine Particle Fraction of Dry Powder Inhalers Using Artificial Neural Networks.

PubMed

Muddle, Joanna; Kirton, Stewart B; Parisini, Irene; Muddle, Andrew; Murnane, Darragh; Ali, Jogoth; Brown, Marc; Page, Clive; Forbes, Ben

2017-01-01

Dry powder inhalers are increasingly popular for delivering drugs to the lungs for the treatment of respiratory diseases, but are complex products with multivariate performance determinants. Heuristic product development guided by in vitro aerosol performance testing is a costly and time-consuming process. This study investigated the feasibility of using artificial neural networks (ANNs) to predict fine particle fraction (FPF) based on formulation device variables. Thirty-one ANN architectures were evaluated for their ability to predict experimentally determined FPF for a self-consistent dataset containing salmeterol xinafoate and salbutamol sulfate dry powder inhalers (237 experimental observations). Principal component analysis was used to identify inputs that significantly affected FPF. Orthogonal arrays (OAs) were used to design ANN architectures, optimized using the Taguchi method. The primary OA ANN r 2 values ranged between 0.46 and 0.90 and the secondary OA increased the r 2  values (0.53-0.93). The optimum ANN (9-4-1 architecture, average r 2 0.92 ± 0.02) included active pharmaceutical ingredient, formulation, and device inputs identified by principal component analysis, which reflected the recognized importance and interdependency of these factors for orally inhaled product performance. The Taguchi method was effective at identifying successful architecture with the potential for development as a useful generic inhaler ANN model, although this would require much larger datasets and more variable inputs. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Determination of optimum values for maximizing the profit in bread production: Daily bakery Sdn Bhd

NASA Astrophysics Data System (ADS)

Muda, Nora; Sim, Raymond

2015-02-01

An integer programming problem is a mathematical optimization or feasibility program in which some or all of the variables are restricted to be integers. In many settings the term refers to integer linear programming (ILP), in which the objective function and the constraints (other than the integer constraints) are linear. An ILP has many applications in industrial production, including job-shop modelling. A possible objective is to maximize the total production, without exceeding the available resources. In some cases, this can be expressed in terms of a linear program, but variables must be constrained to be integer. It concerned with the optimization of a linear function while satisfying a set of linear equality and inequality constraints and restrictions. It has been used to solve optimization problem in many industries area such as banking, nutrition, agriculture, and bakery and so on. The main purpose of this study is to formulate the best combination of all ingredients in producing different type of bread in Daily Bakery in order to gain maximum profit. This study also focuses on the sensitivity analysis due to changing of the profit and the cost of each ingredient. The optimum result obtained from QM software is RM 65,377.29 per day. This study will be benefited for Daily Bakery and also other similar industries. By formulating a combination of all ingredients make up, they can easily know their total profit in producing bread everyday.

Practices of pharmacies that compound extemporaneous formulations.

PubMed

Treadway, Angela K; Craddock, Deeatra; Leff, Richard

2007-07-01

A survey was conducted to characterize the standard of practice for extemporaneous pharmaceutical compounding within community and institutional pharmacies. Extemporaneous compounding practices vary among pharmacies. Because of this, the survey inquired specifically about a single pharmaceutical product (caffeine citrate 20 mg/mL) to minimize variability among respondents. Survey questions were written to identify compounding practice variations with (1) policies and procedures, (2) process validation, (3) personnel education, training, and evaluation, (4) expiration dating, (5) storage and handling of compounded prescriptions within the pharmacy, (6) labeling, (7) facilities and equipment, (8) end-product evaluation, (9) handling of sterile products outside of the pharmacy, (10) aseptic technique and product preparation, and (11) documentation. A total of 522 surveys were mailed; 117 completed surveys were returned and included in the analyses. Over half of the pharmacies surveyed were large institutional pharmacies with daily prescriptions exceeding 300. Almost 71% of pharmacies reported having policies and procedures for compounding and providing compounding training for staff. Almost one third of the pharmacies that responded did not have compounding policies and procedures and did not provide staff training. For those pharmacies that provided training, the methods used were diverse (e.g., lectures and videotapes, external certificate programs). Formulations used to compound caffeine appeared to be diverse as evidenced by the varied addition of inactive ingredients. A survey of compounding pharmacies found variability in overall compounding practices and training and in practices specifically related to compounding preparations of caffeine citrate.

The prediction of human skin responses by using the combined in vitro fluorescein leakage/Alamar Blue (resazurin) assay.

PubMed

Clothier, Richard; Starzec, Gemma; Pradel, Lionel; Baxter, Victoria; Jones, Melanie; Cox, Helen; Noble, Linda

2002-01-01

A range of cosmetics formulations with human patch-test data were supplied in a coded form, for the examination of the use of a combined in vitro permeability barrier assay and cell viability assay to generate, and then test, a prediction model for assessing potential human skin patch-test results. The target cells employed were of the Madin Darby canine kidney cell line, which establish tight junctions and adherens junctions able to restrict the permeability of sodium fluorescein across the barrier of the confluent cell layer. The prediction model for interpretation of the in vitro assay results included initial effects and the recovery profile over 72 hours. A set of the hand-wash, surfactant-based formulations were tested to generate the prediction model, and then six others were evaluated. The model system was then also evaluated with powder laundry detergents and hand moisturisers: their effects were predicted by the in vitro test system. The model was under-predictive for two of the ten hand-wash products. It was over-predictive for the moisturisers, (two out of six) and eight out of ten laundry powders. However, the in vivo human patch test data were variable, and 19 of the 26 predictions were correct or within 0.5 on the 0-4.0 scale used for the in vivo scores, i.e. within the same variable range reported for the repeat-test hand-wash in vivo data.

Impact of interannual variability (1979-1986) of transport and temperature on ozone as computed using a two-dimensional photochemical model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jackman, C.H.; Douglass, A.R., Chandra, S.; Stolarski, R.S.

1991-03-20

Eight years of NMC (National Meteorological Center) temperature and SBUV (solar backscattered ultraviolet) ozone data were used to calculate the monthly mean heating rates and residual circulation for use in a two-dimensional photochemical model in order to examine the interannual variability of modeled ozone. Fairly good correlations were found in the interannual behavior of modeled and measured SBUV ozone in the upper stratosphere at middle to low latitudes, where temperature dependent photochemistry is thought to dominate ozone behavior. The calculated total ozone is found to be more sensitive to the interannual residual circulation changes than to the interannual temperature changes.more » The magnitude of the modeled ozone variability is similar to the observed variability, but the observed and modeled year to year deviations are mostly uncorrelated. The large component of the observed total ozone variability at low latitudes due to the quasi-biennial oscillation (QBO) is not seen in the modeled total ozone, as only a small QBO signal is present in the heating rates, temperatures, and monthly mean residual circulation. Large interanual changes in tropospheric dynamics are believed to influence the interannual variability in the total ozone, especially at middle and high latitudes. Since these tropospheric changes and most of the QBO forcing are not included in the model formulation, it is not surprising that the interannual variability in total ozione is not well represented in the model computations.« less

Self Efficacy and Some Demographic Variables as Predictors of Occupational Stress among Primary School Teachers in Delta State of Nigeria

ERIC Educational Resources Information Center

Akpochafo, G. O.

2014-01-01

This study investigated self efficacy and some demographic variables as predictors of occupational stress among primary school teachers in Delta State. Three hypotheses were formulated to guide the study. The study adopted a descriptive survey design that utilized an expost-facto research type. A sample of one hundred and twenty primary school…

Gain scheduling - Potential hazards and possible remedies

NASA Technical Reports Server (NTRS)

Shamma, Jeff S.; Athans, Michael

1991-01-01

A common gain scheduling rule-of-thumb is to schedule on a slow variable. In this work, it is shown how current gain scheduling practice is necessarily limited to slow variations in the scheduling variable. These limitations are revealed to be consequences of fundamental control concepts. Furthermore, it is shown how a formulation of the gain scheduling procedure can lead toward ultimately removing these restrictions.

Regional agricultural susceptibility to climate variability: A district level analysis of Maharashtra, India

NASA Astrophysics Data System (ADS)

Swami, D.; Parthasarathy, D.; Dave, P.

2016-12-01

Climate variability (CV) has adverse impact on crop production and inadequate research carried out to assess the impact of CV on crop production has aggravated the ability of farmers to adapt (Jones et al., 2000). A better understanding of CV is required to reduce the vulnerability of farmers towards existing and future CV. Further, a wide variation in policies related to climate change exists at global level and considering the state/nation as a single unit for policy formulations may lead to under-representation of regional problems. Hence, the present work chooses to focus on CVassessment at the regional/district level of Maharashtra state in India. Here, interannual variability of wet and dry spells from year 1951-2013, are used as a measure of CV. Statistical declining trend of wet spells for (12/34) districts was observed across all the districts of Maharashtra. Districts showing highest change in wet spell pre and post 1976/77 are Beed, Latur and Osmanabad belong to Central Maharashtra Plateau zone and Western Maharashtra scarcity zone. Dry spells for (8/34) districts were found to statistically increase across all the districts of Maharashtra. Washim, Yavatmal of Vidarbha zone; and Latur, Parbhani of Amravati division belonging to Central Maharashtra Plateau zone and Central Vidarbha zone are found to reflect the large variation in their behavior pre and post 1976/77. Findings reveal that districts from the same agro-climate zones respond differently to CV, indicating significant spatial heterogeneity within the region. Trend in monsoon variability was found to be prominent after 1976/77, suggesting an enhanced role of climate change on climate variability after 1977. It necessitates separate policy formulation related to CV and agriculture for each district to bring out the solution for regional issues (socio-political, farmers, agriculturalists, economical) more clearly. Further we have attempted to link agriculture vulnerability and crop sensitivity to CV. Results signify spatial and temporal variability of different agro-ecological and climate parameters; suitable adaptation measures to famers and policy makers need to address this change. The findings can be utilized by farmers and policy makers while formulating agricultural policies and adaptation measures related to climate change.

Presymplectic current and the inverse problem of the calculus of variations

NASA Astrophysics Data System (ADS)

Khavkine, Igor

2013-11-01

The inverse problem of the calculus of variations asks whether a given system of partial differential equations (PDEs) admits a variational formulation. We show that the existence of a presymplectic form in the variational bicomplex, when horizontally closed on solutions, allows us to construct a variational formulation for a subsystem of the given PDE. No constraints on the differential order or number of dependent or independent variables are assumed. The proof follows a recent observation of Bridges, Hydon, and Lawson [Math. Proc. Cambridge Philos. Soc. 148(01), 159-178 (2010)] and generalizes an older result of Henneaux [Ann. Phys. 140(1), 45-64 (1982)] from ordinary differential equations (ODEs) to PDEs. Uniqueness of the variational formulation is also discussed.

Vector analogues of the Maggi-Rubinowicz theory of edge diffraction

NASA Astrophysics Data System (ADS)

Meneghini, R.; Shu, P.; Bay, J.

1980-10-01

The Maggi-Rubinowicz technique for scalar and electromagnetic fields is interpreted as a transformation of an integral over an open surface to a line integral around its rim. Maggi-Rubinowicz analogues are found for several vector physical optics representations. For diffraction from a circular aperture, a numerical comparison between these formulations shows the two methods are in agreement. To circumvent certain convergence difficulties in the Maggi-Rubinowicz integrals that occur as the observer approaches the shadow boundary, a variable mesh integration is used. For the examples considered, where the ratio of the aperture diameter to wavelength is about ten, the Maggi-Rubinowicz formulation yields an 8 to 10 fold decrease in computation time relative to the physical optics formulation.

Vector analogues of the Maggi-Rubinowicz theory of edge diffraction

NASA Technical Reports Server (NTRS)

Meneghini, R.; Shu, P.; Bay, J.

1980-01-01

The Maggi-Rubinowicz technique for scalar and electromagnetic fields is interpreted as a transformation of an integral over an open surface to a line integral around its rim. Maggi-Rubinowicz analogues are found for several vector physical optics representations. For diffraction from a circular aperture, a numerical comparison between these formulations shows the two methods are in agreement. To circumvent certain convergence difficulties in the Maggi-Rubinowicz integrals that occur as the observer approaches the shadow boundary, a variable mesh integration is used. For the examples considered, where the ratio of the aperture diameter to wavelength is about ten, the Maggi-Rubinowicz formulation yields an 8 to 10 fold decrease in computation time relative to the physical optics formulation.

Linear complementarity formulation for 3D frictional sliding problems

USGS Publications Warehouse

Kaven, Joern; Hickman, Stephen H.; Davatzes, Nicholas C.; Mutlu, Ovunc

2012-01-01

Frictional sliding on quasi-statically deforming faults and fractures can be modeled efficiently using a linear complementarity formulation. We review the formulation in two dimensions and expand the formulation to three-dimensional problems including problems of orthotropic friction. This formulation accurately reproduces analytical solutions to static Coulomb friction sliding problems. The formulation accounts for opening displacements that can occur near regions of non-planarity even under large confining pressures. Such problems are difficult to solve owing to the coupling of relative displacements and tractions; thus, many geomechanical problems tend to neglect these effects. Simple test cases highlight the importance of including friction and allowing for opening when solving quasi-static fault mechanics models. These results also underscore the importance of considering the effects of non-planarity in modeling processes associated with crustal faulting.

Practical optimal flight control system design for helicopter aircraft. Volume 2: Software user's guide

NASA Technical Reports Server (NTRS)

Riedel, S. A.

1979-01-01

A method by which modern and classical control theory techniques may be integrated in a synergistic fashion and used in the design of practical flight control systems is presented. A general procedure is developed, and several illustrative examples are included. Emphasis is placed not only on the synthesis of the design, but on the assessment of the results as well. The first step is to establish the differences, distinguishing characteristics and connections between the modern and classical control theory approaches. Ultimately, this uncovers a relationship between bandwidth goals familiar in classical control and cost function weights in the equivalent optimal system. In order to obtain a practical optimal solution, it is also necessary to formulate the problem very carefully, and each choice of state, measurement and output variable must be judiciously considered. Once design goals are established and problem formulation completed, the control system is synthesized in a straightforward manner. Three steps are involved: filter-observer solution, regulator solution, and the combination of those two into the controller. Assessment of the controller permits and examination and expansion of the synthesis results.

Analytical formulation of directly modulated OOFDM signals transmitted over an IM/DD dispersive link.

PubMed

Sánchez, C; Ortega, B; Wei, J L; Tang, J; Capmany, J

2013-03-25

We provide an analytical study on the propagation effects of a directly modulated OOFDM signal through a dispersive fiber and subsequent photo-detection. The analysis includes the effects of the laser operation point and the interplay between chromatic dispersion and laser chirp. The final expression allows to understand the physics behind the transmission of a multi-carrier signal in the presence of residual frequency modulation and the description of the induced intermodulation distortion gives us a detailed insight into the diferent intermodulation products which impair the recovered signal at the receiver-end side. Numerical comparisons between transmission simulations results and those provided by evaluating the expression obtained are carried out for different laser operation points. Results obtained by changing the fiber length, laser parameters and using single mode fiber with negative and positive dispersion are calculated in order to demonstrate the validity and versatility of the theory provided in this paper. Therefore, a novel analytical formulation is presented as a versatile tool for the description and study of IM/DD OOFDM systems with variable design parameters.

Design and characterization of sustained release ketoprofen entrapped carnauba wax microparticles.

PubMed

Oliveira, Rodinelli B; Nascimento, Thais L; Lima, Eliana M

2012-01-01

Ketoprofen is a non-steroid anti-inflammatory drug (NSAID) used in the treatment of rheumatic diseases and in mild to moderate pain. Ketoprofen has a short biological half-life and the commercially available conventional release formulations require dosages to be administered at least 2-3 times a day. Due to these characteristics, ketoprofen is a good candidate for the preparation of controlled release formulations. In this work, a multiparticulate-sustained release dosage form containing ketoprofen in a carnauba wax matrix was developed. Particles were prepared by an emulsion congealing technique. System variables were optimized using fractional factorial and response surface experimental design. Characterization of the particles included size and morphology, flow rate, drug loading and in vitro drug release. Spherical particles were obtained with high drug load and sustained drug release profile. The optimized particles had an average diameter of approximately 200 µm, 50% (w/w) drug load, good flow properties and prolonged ketoprofen release for more than 24 h. Carnauba wax microspheres prepared in this work represent a new multiparticulate-sustained release system for the NSAID ketoprofen, exhibiting good potential for application in further pharmaceutical processes.

Evaluation of an Evidence-based Medicine Educational Program for Pharmacists and Pharmacy Students.

PubMed

Shimizu, Tadashi; Ueda, Masahiro; Toyoyama, Mikoto; Ohmori, Shiho; Takagaki, Nobumasa

2017-01-01

This study evaluated the effect of an evidence-based medicine (EBM) educational program on EBM-related knowledge and skills of pharmacists and pharmacy students. Our preliminary educational program included the following four sessions: 1) ice breaker, 2) formulation of answerable clinical questions from virtual clinical scenario using the PICO criteria, 3) critical appraisal of the literature using a checklist, and 4) critical appraisal of the results and integrating the evidence with experience and patients values. Change in knowledge and skills related to EBM were evaluated using pre- and post-seminar 4-point scale questionnaires comprising of 14 questions. A total of 23 pharmacists, 1 care manager, and 5 pharmacy students participated in our EBM educational seminar. Knowledge and skills related to several variables improved significantly post-seminar (pre-seminar 2.80 versus 3.26 post-seminar; p<0.001). Specifically, the skills of formulating answerable clinical questions from virtual clinical scenario and critical appraisal of the literature using a checklist improved. Our findings suggested that EBM educational program using problem-based learning was effective in improving EBM-related knowledge and skills of pharmacists and pharmacy students.

Data-Driven Modeling and Prediction of Arctic Sea Ice

NASA Astrophysics Data System (ADS)

Kondrashov, Dmitri; Chekroun, Mickael; Ghil, Michael

2016-04-01

We present results of data-driven predictive analyses of sea ice over the main Arctic regions. Our approach relies on the Multilayer Stochastic Modeling (MSM) framework of Kondrashov, Chekroun and Ghil [Physica D, 2015] and it leads to probabilistic prognostic models of sea ice concentration (SIC) anomalies on seasonal time scales. This approach is applied to monthly time series of state-of-the-art data-adaptive decompositions of SIC and selected climate variables over the Arctic. We evaluate the predictive skill of MSM models by performing retrospective forecasts with "no-look ahead" for up to 6-months ahead. It will be shown in particular that the memory effects included intrinsically in the formulation of our non-Markovian MSM models allow for improvements of the prediction skill of large-amplitude SIC anomalies in certain Arctic regions on the one hand, and of September Sea Ice Extent, on the other. Further improvements allowed by the MSM framework will adopt a nonlinear formulation and explore next-generation data-adaptive decompositions, namely modification of Principal Oscillation Patterns (POPs) and rotated Multichannel Singular Spectrum Analysis (M-SSA).

N-mix for fish: estimating riverine salmonid habitat selection via N-mixture models

USGS Publications Warehouse

Som, Nicholas A.; Perry, Russell W.; Jones, Edward C.; De Juilio, Kyle; Petros, Paul; Pinnix, William D.; Rupert, Derek L.

2018-01-01

Models that formulate mathematical linkages between fish use and habitat characteristics are applied for many purposes. For riverine fish, these linkages are often cast as resource selection functions with variables including depth and velocity of water and distance to nearest cover. Ecologists are now recognizing the role that detection plays in observing organisms, and failure to account for imperfect detection can lead to spurious inference. Herein, we present a flexible N-mixture model to associate habitat characteristics with the abundance of riverine salmonids that simultaneously estimates detection probability. Our formulation has the added benefits of accounting for demographics variation and can generate probabilistic statements regarding intensity of habitat use. In addition to the conceptual benefits, model application to data from the Trinity River, California, yields interesting results. Detection was estimated to vary among surveyors, but there was little spatial or temporal variation. Additionally, a weaker effect of water depth on resource selection is estimated than that reported by previous studies not accounting for detection probability. N-mixture models show great promise for applications to riverine resource selection.