Determination of Impurities in Pharmaceuticals: Why and How?

The presence of impurities, particularly the API-related impurities, i.e., degradation-related impurities (DRIs) and interaction-related impurities (IRIs), may affect the quality, safety, and efficacy of drug products. Since the regulatory requirements and management strategies are required to be established and complied, sources of impurities shall be carefully classified prior to take subsequent steps such as development of analytical methods and acceptance criteria. Current international regulatory requirements for the management of impurities in pharmaceuticals were reviewed. Procedures for the identification of DPIs in pharmaceuticals, i.e., ethyl cysteinate dimer, (R)-N-methyl-3-(2-bromophenoxy)-3-phenylpropanamine, sestamibi, etc., using high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS) were studied. Scheme for the establishment of analytical methods and acceptance criteria of process-related impurities (PRIs) and DRIs in accordance with the requirements of International Council for Harmonization (ICH) and algorithm to perform the identification of DPIs by using LC-MS/MS has been proposed. Practice of kinetic study to distinguish PRIs and DRIs, determination of the potential core fragments coupled with a predicted list of relevant transformations for conducting MS/MS scans, applications of stable isotope distribution patterns or natural abundances, practice of mass balance, etc., have been well demonstrated to justify the reliabilities of identification results

A passive control method of HAWT blade cyclical aerodynamic load induced by wind shear

Abstract: Modern wind turbines are mainly horizontal axis and operate in bottom atmospheric boundary layer driven by wind shear flow, therefore as the blades rotating the aerodynamic load vary cyclically, with horizontal axis wind turbine (HAWT) large-scaling the cyclical characteristic becomes more obvious, shortening blade life and increasing cost of wind turbine. As the development of wind turbine largescaling is the essential trend, load fluctuation control is more and more critical in HAWT design and manufacture. In common, individual pitch control is introduced to solve the problem, but cost much energy from electric net. In this paper, a concept of telescopic blade root is introduced to reduce fluctuate load induced by wind shear passively, and considering the blades as rigid assessment is operated, meanwhile aerodynamic model based on blade element method in order to analysis the aerodynamic load on NREL Phase VI reference based blade. The result shows that after introducing the equipment the blade fatigue load can be released, lengthening blade life

Computer anxiety

The fear or apprehension experienced by people when they plan to interact, or actually interact, with computers is called computer anxiety (Rohner & Simonson, 1981). The purpose of this paper is to review the literature on computer anxiety, the factors that influence it, and the methods to reduce its effects

Thermal performance of heat pipe drill : experimental study

Abstract: An experimental study is performed in this paper to verify the concept of thermal management of using a heat pipe in the drilling process. The basic idea is to insert a heat pipe at the center of the drill tool with the evaporator located close to the drill tip, and condenser located at the end of the drill. In this way, heat accumulated in the drill tip can be transported to the remote section of the drill and remove it there to the tool holder, which attaches the drill. Temperatures at the drill tip as well as tool wear can be reduced significantly. In this paper, experimental investigations on a heat pipe drill for various heat flux inputs, inclination angles and rotating speeds are presented. The effect of contact resistance and tool holder (acting as heat sink) on heat pipe performance will also be demonstrated. The results presented in this paper may be used for important design and practical implementation consideration

Heat transfer performance of lithium bromide solution in falling film generator

An experimental investigation of vertical in-tube falling film heat transfer with different heat fluxes and concentrations of lithium bromide solution were conducted. The experiments show that the heat transfer coefficient increases with the decrease of inlet concentration and significantly increase with heat flux increase. An experimental correlation of falling film heat transfer coefficient is obtained.The comparison of falling film generator with immersed tube generator shows that the heat transfer coefficient is 4.37 times higher than that of immersed tube generator, which can significantly reduce the volume of the falling film generator. The volume of falling film generator is only 52.1% of the volume of immersed tube generator

Heat transfer and pressure drop experimental correlations for air-water bubbly flow

In this paper, a novel air–water bubbly flow heat transfer experiment is performed to investigate the characteristics of pressure drop of airflow and heat transfer between water and tubes for its potential application in evaporative cooling. The attempts to reduce the pressure drop while maintaining higher heat transfer coefficient have been achieved by decreasing the bubble layer thickness through the water pump circulation. Pressure drops of air passing through the sieve plate and the bubbling layer are measured for different height of bubble layer, hole–plate area ratio of the sieve plate and the superficial air velocity. Experimental data show that the increase of bubble layer height and air velocity both increase the pressure drop while the effect of the hole–plate area ratio of the sieve plate on the heat transfer coefficient is relatively sophisticated. A pressure drop correlation including the effects of all the tested parameters is proposed, which has a mean absolute deviation of 14.5% to that of the experimental data. Heat transfer coefficients of the water and the outside tube wall are measured and the effects of superficial air velocity, heat flux and bubble layer height are also examined. Through a dimensional analysis, a heat transfer correlation with a mean absolute deviation of 9.7% is obtained based on experimental data

Particle bonding mechanism in CGDS-a three-dimensional approach

Abstract: Cold gas dynamics spray (CGDS) is a surface coating process using highly accelerated particles to form the surface coating by high speed impact of the particles. In the CGDS process, metal particles of generally 1-50 μm diameter is carried by a gas stream in high pressure (typically 20-30 atm) through a DE Laval type nozzle to achieve supersonic flying so as to impact on the substrate. Typically, the impact velocity ranges between 300 and 1200 m/s in the CGDS process. When the particle gains its critical velocity, the minimum in-flight speed at which it can deposit, adiabatic shear instabilities will occur. Herein, to ascertain the critical velocities of different particle sizes on the bonding efficiency in CGDS process, three-dimensional numerical simulations of single particle deposition process were performed. In the CGDS process, one of the most important parameters which determine the bonding strength with the substrate is particle impact temperature. Bonding will occur when the particle’s impacting velocity surpass the critical velocity, at which the interface can achieve 60 % of melting temperature of particle material (Ref 1). Therefore, critical velocity should be a main parameter on the coating quality. The particle critical velocity is determined not only by its size, but also by its material properties. This study numerically investigate the critical velocity for the particle deposition process in CGDS. In the present numerical analysis, copper (Cu) was chosen as particle material and aluminum (Al) as substrate material for this study. The impacting velocities were selected between 300 m/s and 800 m/s increasing in steps of 100 m/s. The simulation result reveals temporal and spatial interfacial temperature distribution and deformation between particle(s) and substrate. Finally, comparison is carried out between the computed results and experimental data

The acceleration of micro- and nano-particles in supersonic De-Laval-Type nozzle

The particle velocity in cold gas dynamic spraying (CGDS) is one of the most important factors that can determine the properties of the bonding to the substrate. The acceleration of gas to particles is strongly dependent on the densities of particles and the particle size. In this paper, the acceleration process of micro-scale and nano-scale copper (Cu) and platinum (Pt) particles in De-Laval-Type nozzle is investigated. A numerical simulation is performed for the gas-particle two phase flow with particle diameter ranging from 100nm to 50µm, which are accelerated by carrier gas Nitrogen in a supersonic DeLaval-type nozzle. The results show that cone-shape weak shocks (compression waves) occur at the exit of divergent section and the particle density has significant effect on the accele ration of micro-scale particles. At same inlet condition, the velocity of the smaller particles is larger than the larger particles at the exit of the divergent section of the nozzle

Numerical investigations on cold gas dynamic spray process with nano- and microsize particles

The particle velocity in cold gas dynamic spraying (CGDS) is one of the most important factors that can determine the properties of the bonding to the substrate. In this paper, the acceleration process of microscale and sub-microscale copper (Cu) and platinum (Pt) particles inside and outside De-Laval-Type nozzle is investigated. A numerical simulation is performed for the gas-particle two phase flow with particle diameter ranging from 100 nm to 50 lm, which are accelerated by carrier gas nitrogen and helium in a supersonic De-Laval-type nozzle. The carrier gas velocity and pressure distributions in the nozzle and outside the nozzle are illustrated. The centerline velocity for two types of particles, Pt and Cu, are demonstrated. It is observed that the existence of the bow shocks near the substrate prevents the smaller size particles (less than 0.5 lm) from penetrating, thus leads to poor coating in the actual practices. Furthermore, the extended straight section may have different optimal length for different size particles, and even may be unnecessary for sub-microsize particles