Development and Preliminary Experience with an Ease of Extractability Rating System for Prescription Opioids

Abstract

One important factor in the abuse potential of an opioid product is the ease with which active drug can be extracted. There are currently no standards for testing or reporting extractability. This article describes the development of an Extractability Rating System for use by the pharmaceutical industry and regulators. Despite several limitations, this effort serves as a call for standardized testing and reporting so that products can be accurately rated, and should help establish goals for drug developers who wish to develop “abuse-resistant” opioid products.     

Effectiveness and benefit-cost of peer-based workplace substance abuse prevention coupled with random testing

Few studies have evaluated the impact of workplace substance abuse prevention programs on occupational injury, despite this being a justification for these programs. This paper estimates the effectiveness and benefit-cost ratio of a peer-based substance abuse prevention program at a U.S. transportation company, implemented in phases from 1988 to 1990. The program focuses on changing workplace attitudes toward on-the-job substance use in addition to training workers to recognize and intervene with coworkers who have a problem. The program was strengthened by federally mandated random drug and alcohol testing (implemented, respectively, in 1990 and 1994). With time-series analysis, we analyzed the association of monthly injury rates and costs with phased program implementation, controlling for industry injury trend. The combination of the peer-based program and testing was associated with an approximate one-third reduction in injury rate, avoiding an estimated $48 million in employer costs in 1999. That year, the peer-based program cost the company $35 and testing cost another $35 per employee. The program avoided an estimated $1850 in employer injury costs per employee in 1999, corresponding to a benefit-cost ratio of 26:1. The findings suggest that peer-based programs buttressed by random testing can be cost-effective in the workplace.     

Development of an ultra-high vacuum system for space application

The aim of this paper is to present the development of a very specific ultra-high vacuum system for the space application PHARAO. In order to reach the specified pressure (2.6×10⁻⁸ Pa) during 3 years in a self-contained system, specific solutions have been developed. A calculation of partial pressures of different chemical species (typically hydrogen, rare gases and cesium) in the different areas of the vacuum tube has been computed. Experiments have been also performed in order to verify the possibility of using different kind of materials (outgassing rates of bulk and porous titanium, silicon carbide reinforced aluminum, graphite, etc.) and pumping systems such as getters and a specially developed ion pump.     

Development of an ejector cooling system with thermal pumping effect

This paper presents a feasibility study of an ejector cooling system (ECS) that utilizes a multi-function generator (MFG) to eliminate the mechanical pump. The MFG serves as both a pump and a vapor generator. The MFG is designed based on the pressure equilibration between high and low pressures through heating and cooling process. In this design, an ECS that contains no moving components and is entirely powered by heat can be practicable. A prototype using refrigerant R141b as working fluid was constructed and tested in the present study. The experimental results showed that the system coefficient of performance (COP_o) was 0.218 and the cooling capacity was 0.786 kW at generating temperature (T_G) 90 °C, condensing temperature (T_C) 32.4 °C and evaporating temperature (T_E) 8.2 °C. While taking into account the extra heat needed for the MFG operation, the total coefficient of performance (COP_t) is 0.185. It is shown that a continuous operation for the generation of cooling effect in an ECS with MFG can be achieved. This cooling machine can be very reliable since there is no moving part.     

Development of an ice container system for temporary space cooling

In this study, a system for the simple cooling of temporary spaces using ice was evaluated with the two cooling methods of natural and forced circulation. First, the predicted cooling capacity was calculated. The results indicated the suitability of the forced circulation type for buildings with high cooling loads and the natural circulation type for those with low cooling loads. The outcomes of preliminary experiments for verification of applicability to actual space cooling were also examined, and roughly confirmed the accuracy of the calculated cooling capacity. This system was actually introduced for space cooling at a real exhibition, and its performance was monitored. The results of the measurements taken indicated that it is capable of providing sufficient cooling capacity for temporary prefabricated buildings.     

Polymeric nanospheres fabricated with natural emulsifiers for clinical administration of an anticancer drug paclitaxel (Taxol®)

Paclitaxel (Taxol®) is one of the most effective anticancer drugs found from nature in recent decades, which can treat various cancers including ovarian, breast, brain, colon and lung cancer, and AIDS-related cancer. Due to its low aqueous solubility, adjuvants such as Cremophor EL, which causes serious side effects, have to be used in its administration. Our aim is to develop an alternative delivery system to achieve better therapeutic effects with minimum side effects. Paclitaxel-loaded nanospheres of biodegradable polymers were prepared by an improved solvent extraction/evaporation technique. Phospholipids, cholesterol and vitamins were used to replace traditional chemical emulsifiers to achieve high encapsulation efficiency (EE) and desired release rate of the drug. Nanospheres prepared under various conditions are characterized by the light scattering for size and size distribution, the scanning electron microscopy (SEM) and the atomic force microscopy (AFM) for surface morphology; differential scanning calorimetry (DSC) for the physical status of the drug within the polymeric matrix; the zeta-potential measurement for the surface charge properties; and X-ray photoelectron spectroscopy (XPS) for the surface chemistry. In-vitro release kinetics were measured by high-performance liquid chromatography (HPLC). Best design was pursued to develop a product for cancer chemotherapy.     

基于Lex和Yacc的开放式并联机床后置处理系统开发

针对常见数控系统的后置处理模块具有专用、封闭等特点,从而限制了其在新型并联加工装备中的应用的问题,研究了开放式并联机床后置处理系统开发的关键环节.首先,基于Lex和Yacc编译工具实现了数控代码的解析功能,此功能能够适用于不同体系的数控代码格式,提高数控系统的开放性和通用性.其次,对并联机床后置处理中的关键算法进行了研...     

Development of an automatic method for americium and plutonium separation and preconcentration using an multisyringe flow injection analysis-multipumping flow system

A new procedure for automatic separation and preconcentration of 241Am and 239+240Pu from interfering matrixes using transuranide (TRU)-resin is proposed. Combination of the multisyringe flow injection analysis and multipumping flow system techniques with the TRU-resin allows carrying out the sampling treatment and separation in a short time using large sample volumes. Americium is eluted from the column with 4 mol L(-1) hydrochloric acid, and then plutonium is separated via on-column Pu(IV) reduction to Pu(III) with titanium(III) chloride. The corresponding alpha activities are measured off-line, with a relative standard deviation of 3% and a lower limit of detection of 0.004 Bq mL(-1), by using a multiplanchet low-background proportional counter.     

Production and subcontracting control for an unreliable manufacturing system with setups

This paper deals with the problem of joint production, setup and subcontracting control of unreliable manufacturing systems producing two product types. The production requires setups each time it switches from one product type to another. Subcontracting is an integral part of the decision-making process due to limited production capacity in existing facility. The objective is to propose an effective control policy for the considered system which simultaneously manages production, setup and subcontracting activities. The complexity of the problem lies in the interaction between internal manufacturing decisions and subcontracting that outsource a part of the production, in a dynamic and stochastic environment. An experimental optimisation approach is adopted to determine the optimal control parameters which minimise the average total cost. Extensive sensitivity analyses are performed to illustrate the robustness and the usefulness of the adopted approach. An in-depth study comparing five control policies across a wide range of system parameters is also conducted. Extended cases closer to reality are also investigated considering elements such as the preventive maintenance and the production of non-conforming products. The best control policy in terms of economic performance is then obtained. Valuable insights providing a better understanding of interactions involving production, setup, and subcontracting are discussed.     

低温热水地板辐射采暖事故分析与经验总结

针对新建小区地板辐射采暖系统漏水事故,从施工图设计、安装施工、工程验收、采暖试运行到正式运行各个环节对事故进行全方面的分析研究。分析结果表明,地板辐射采暖系统对施工质量的要求很高,系统爆管、漏水的原因主要来自施工过程,按照《地面辐射供暖技术规程》标准选择的管材不存在漏水的问题,施工和验收是质量控制的重点工作。     

Development of a magnetron sputtering system with an extraordinary strong magnetic field near the target

We have developed a planar sputtering device that uses a melt-processed bulk superconductor to generate the magnetic field. The magnetic field that confines the plasma above the sputtering target is about 1.0 T, which is about 20 times larger than the field normally used for magnetron sputtering. Because of the large magnetic field, discharge at an Ar gas pressure as low as 10⁻³ Pa was possible. In this study, we used the ultra-strong-field sputtering technique for depositing Ga-doped ZnO which is attracting interest as a transparent electrode material. We also studied the effect of employing an auxiliary coil to tailor the magnetic field distribution and discuss how the discharge characteristic had changed.     

区间参数智能梁结构开环系统动力特性分析

以区间参数压电智能梁结构为研究对象,在材料性能参数和几何尺寸为区间变量时采用区间分析法建立了结构质量矩阵和刚度矩阵的区间模型。从求解结构振动动态特性的Rayleigh商出发,利用区间变量运算法则推导出了结构开环系统固有频率的数字特征表达式。通过算例,考察了区间参数对结构固有频率特性的影响,验证了所建模型和方法的可行性与合理性。研究结果表明,文中利用区间系数分析法来研究压电智能梁结构开环系统的动力特性具有一定的工程应用价值。     

Optimal ordering and pricing policy for an inventory system with order cancellations

This paper investigates the problem of ordering and pricing over a finite time planning horizon for an inventory system with advance sales and spot sales. It is assumed that the planning horizon is divided into several sales cycles each of which is divided into an advance sales period and a spot sales period. During the advance sales period, all customers are required to make reservations for their orders and will receive them at the arrival time of the replenishment orders. In the case of the spot sales periods, all customers receive their orders at the time of the purchase. In actual practice, since customers with reservations may cancel their orders before receiving them, this paper considers this phenomenon and develops a continuous time inventory model to deal with the proposed problem. This paper maximizes the total profit over a finite time planning horizon by determining the optimal advance sales price, spot sales price, order size, and replenishment frequency. Analysis of results shows that a simple algorithm can be developed to arrive at an optimal decision.     

Development of an automated process planning and production activity control system for the manufacturing of engineered work surfaces

This paper describes the design and implementation of an Automated Process Planning and Production Activity Control system for a make-to-order business and presents a formal methodology for the development of integrated manufacturing systems. The research is based on concepts developed in a project undertaken in a job shop Case Study facility, producing precision-engineered work surfaces. Industry today is facing numerous challenges on many fronts demanding improved availability and dissemination of processing information. On the demand side there is increased pressure on the manufacturer to meet deadlines and provide the customer with a prompt, efficient service, with accurate lead-time information, and a product of the utmost quality, on time. On the supply side there is increasing competition, variety in the market, a diverse product range, varying processing times and extremely short lead times. The nature of today's business world means that real-time information is a requirement and not an extra. This paper documents the design, structure and implementation of an Automated Process Planning system, which completely automates and integrates Order Entry stages from order receipt to order release. The developed system, namely the Manufacturing Optimization Information System, or MOIS, relays information to and from shop floor operators via a Production Activity Control system at each of the manufacturing stations. The MOIS is part of ongoing research endeavouring to integrate order processing, Process Planning and production control activities with a combined dynamic scheduling and material optimization module in a holistic manufacturing optimization system. The two specific aims of this paper are very clear; first, to bridge the theory-practice gap between theoretical concepts and real industrial issues surrounding Process Planning and Production Control. Secondly, to outline the design, structure and evolution of an integrated Automatic Process Planning and Production Activity Control system, installed in a make-to-order enterprise.     

Formulation development and human in vitro-in vivo correlation for a novel, monolithic controlled-release matrix system of high load and highly water-soluble drug niacin

Novel, controlled-release formulations for high drug load, highly water soluble compound niacin based on polyethylene oxide (PEO) and hydroxypropylmethyl cellulose (HPMC) matrices were developed and investigated. The effect of sodium bicarbonate as a modulator of swelling, erosion, and drug release and its impact on changes in the kinetics of axial swelling and gel strength were evaluated by textural analysis during dissolution study. The drug release rate from PEO-based matrices was faster and correlated with lower gel strength, greater water uptake, and greater matrix erosion. Slower release rate and greater release duration correlated significantly with greater matrix swelling with negligible matrix erosion for the HPMC-based matrix system. Inclusion of sodium bicarbonate in the polymeric matrix salted out the macromolecules and increased gel strength and gel viscosity, especially in the vicinity of the swelling fronts. An in vivo study in human subjects after administration of the formulations and a commercial product exhibited similar plasma concentrations. For the formulation of interest, the mean drug fraction absorbed by the body was calculated by the Wagner-Nelson technique, and a level A “in vitro-in vivo correlation” was observed between the percent released in vitro and percent absorbed in vivo. The developed formulations appear to be robust and easy to manufacture with maximum flexibility with respect to drug dose, polymeric carriers, duration, and kinetics of drug release.     

空分设备制氩系统优化操作的理论依据和经验

分析空分设备制氩系统优化操作的理论依据,介绍制氩过程遇到的问题及处理方法。     

某火星探测器星外材料液氦温区贮存试验系统的研制与试验验证

为了考核某火星探测器星外材料在深冷宇宙空间中的性能,研制了一套用于液氦温区的试验装置,进行了环境模拟试验研究,结果表明该装置能满足试验要求.同时得到了液氦表面温度沿高度方向的变化规律.     

Development of an active packaging with molecularly imprinted polymers for beef preservation

To develop molecularly imprinted polymers (MIPs) for new food packaging material, a new active antibacterial packaging material was prepared with allyl isothiocyanate MIPs (AITC‐MIPs) and chitosan (CS) for beef preservation. AITC‐MIPs were prepared with AITC as template, β‐CD as the functional monomer, and TDI as the cross‐linker by the non‐covalent method, and the release characteristics were evaluated under different relative humidities and temperatures. The AITC‐MIPs active packaging film was obtained by uniform coating with CS coating solution and AITC‐MIPs based on the surface of the original low‐density polyethylene packaging film, and its role in delaying muscle metamorphism was thoroughly explored. According to the N‐hexane extraction method, the AITC content in AITC‐MIPs was determined to be 73.9 μL/g. The release behaviors of AITC‐MIPs under different humidities could be obtained by fitting with Avrami's Equation. The release of AITC‐MIPs under the relative humidities of 98% and 75% is a restricted dynamic diffusion process, while the release behaviors of AITC‐MIPs under the relative humidity of 50% are between those of a diffusion process and those of a first‐order mode dynamic process. The AITC‐MIPs could endure the heat stress, and the lower temperature was conducive to the stability of the AITC‐MIPs. A series of physicochemical and microbiological indicators fully illustrated that muscle deterioration could be significantly (P < 0.05) postponed by AITC‐MIPs active packaging film compared with the original low‐density polyethylene packaging film.     

室温磁制冷往复式系统控制采集系统开发

介绍室温磁制冷系统的流程。在往复式室温磁制冷系统实验台中用模块化方法分别开发针对电磁阀、步进电机和变频器的控制系统以及温度、流量和压力的采集系统,并集成开发采集控制的软件系统。