Application of USP Inlet Extensions to the TSI Impactor System 3306/3320 Using HFA 227 Based Solution Metered Dose Inhalers

ABSTRACT

The objective of this study was to further evaluate the need for a vertical inlet extension when testing solution metered dose inhalers using the TSI Model 3306 Impactor Inlet in conjunction with the TSI Model 3320 Aerodynamic Particle Sizer (APS). The configurations tested using the TSI system were compared to baseline measurements that were performed using the Andersen Mark II 8-stage cascade impactor (ACI). Seven pressurized solution metered dose inhalers were tested using varied concentrations of beclomethasone dipropionate (BDP), ethanol, and HFA 227 propellant. The inhalers were tested with the cascade impactor, and with the TSI system. The TSI system had three different configurations as the manufacturer provided (0 cm) or with inlet extensions of 20 and 40 cm. The extensions were located between the USP inlet and the Model 3306 Impactor Inlet. There were no practical differences between each system for the stem, actuator, or USP inlet. The fine particle mass (aerodynamic mass < 4.7 µm) was affected by extension length and correlated well with the ACI when an extension was present. APS particle size measurements were unaffected by the extension lengths and correlated well to particle size determined from the ACI analysis. It has been confirmed that an inlet extension may be necessary for the TSI system in order to give mass results that correlate to the ACI, especially for formulations having significant concentrations of low volatility excipients. Additionally, the results generated from this study were used to evaluate the product performance of HFA 227 based solution formulations that contain varying concentrations of ethanol as a cosolvent.     

Comparison of the TSI Model 3306 Impactor Inlet with the Andersen Cascade Impactor: solution metered dose inhalers

The product performance of a series of solution Metered Dose Inhalers (MDIs) were evaluated using the TSI Model 3306 Impactor Inlet and the Andersen Cascade Impactor (ACI). The goal of the study was to test whether the fine particle and coarse particle depositions obtained using the Model 3306 were comparable to those results obtained by ACI testing. The analysis using the Model 3306 was performed as supplied by the manufacturer as well as with 20 cm and 40 cm vertical extensions that were inserted between the Model 3306 and the USP Inlet. Nine different solution formulations were evaluated. The drug concentrations ranged from 0.08 to 0.8% w/w and the ethanol cosolvent concentration varied between 5 and 20% w/w. In general, it was found that good correlations between the two instruments were obtained. However, for formulations containing 10-20% w/w ethanol it is shown that an extension fitted to the Model 3306 yielded an improved correlation to those obtained from the ACI.     

Optimizing the primary particle size distributions of pressurized metered dose inhalers by using inkjet spray drying for targeting desired regions of the lungs

Conventional suspension pressurized metered dose inhalers (pMDIs) suffer not only from delivering small amounts of a drug to the lungs, but also the inhaled dose scatters all over the lung regions. This results in much less of the desired dose being delivered to regions of the lungs. This study aimed to improve the aerosol performance of suspension pMDIs by producing primary particles with narrow size distributions. Inkjet spray drying was used to produce respirable particles of salbutamol sulfate. The Next Generation Impactor (NGI) was used to determine the aerosol particle size distribution and fine particle fraction (FPF). Furthermore, oropharyngeal models were used with the NGI to compare the aerosol performances of a pMDI with monodisperse primary particles and a conventional pMDI. Monodisperse primary particles in pMDIs showed significantly narrower aerosol particle size distributions than pMDIs containing polydisperse primary particles. Monodisperse pMDIs showed aerosol deposition on a single stage of the NGI as high as 41.75?±?5.76%, while this was 29.37?±?6.79% for a polydisperse pMDI. Narrow size distribution was crucial to achieve a high FPF (49.31?±?8.16%) for primary particles greater than 2?µm. Only small polydisperse primary particles with sizes such as 0.65?±?0.28?µm achieved a high FPF with (68.94?±?6.22%) or without (53.95?±?4.59%) a spacer. Oropharyngeal models also indicated a narrower aerosol particle size distribution for a pMDI containing monodisperse primary particles compared to a conventional pMDI. It is concluded that, pMDIs formulated with monodisperse primary particles show higher FPFs that may target desired regions of the lungs more effectively than polydisperse pMDIs.     

在动态称重中应用基于声卡的数据采集系统

针对定量包装对精度和速度的要求,建立了混合式动态定量称重系统;构建了基于声卡的数据采集系统,介绍了系统软硬件结构,并将数据采集系统应用于动态称重中,实验证明了该方法的可行性.     

Production of double-layer epitaxial structures based on the solid solution of the Cd-Hg-Te system using a combination of LPE and MOCVD techniques

The technique of growing CdTe and Cd _x Hg_{1 ? x} Te layers utilizing chemical metalloorganic compound vapor deposition (MOCVD) onto a CdZnTe(111) substrate with a preliminarily deposited Cd _y Hg_{1 ? y} Te layer using liquid phase epitaxy (LPE) has been developed. No noticeable changes in the electrophysical parameters and composition of the Cd _y Hg_{1 ? y} Te layer take place under such conditions during MOCVD deposition.     

自然冷却换热技术在电信行业通信机房空调系统中的应用研究

以北京市某既有电信行业通信机房为研究对象,针对北京地区的气候条件以及通信机房的空调负荷特性,基于自然冷却换热技术的基本理论与原理,对该通信机房原有的空调方式进行节能改造,在原有的单一空调系统基础上新增自然冷却换热系统。2009年秋季供冷工况运行结果表明,所提出的应用方案不但可以满足通信机房气流组织以及使用功能要求,而且节能效果显著。     

Application of the mixed approximation to the solution of two-dimensional problems of the theory of small elastoplastic strains using the finite element method

A triangular finite element that provides the stability and convergence of the mixed approximation is used for the solution of two-dimensional boundary-value problems of the theory of small elastoplastic strains. A system of resolving matrix equations of a mixed type is presented for the solution of which a three-layer iteration algorithm with a preconditioning matrix is used. Numerical results for the solution of model problems obtained by the classical and combined finite element methods are compared. __________ Translated from Problemy Prochnosti, No. 2, pp. 124–136, March–April, 2006.     

Application of mixed variational formulations based on the finite element method to the solution of problems on natural vibrations of elastic bodies

We consider mixed variational formulations and the application of the mixed approximations of the finite element method to the solution of problems on natural vibrations of elastic bodies. To solve the generalized spectral problem, three forms of the mixed variational formulations are proposed. The correctness and stability of mixed variational formulations for displacements, strains and stresses are investigated. Matrix equations of the mixed method are given whose solution is performed using the modified algorithm of the steepest descent method. The results of calculations for natural frequencies of free vibrations of a straight and a circular beam are presented that are obtained in the solution of the problem in a two-dimensional formulation based on the classical and mixed finite-element method approaches. __________ Translated from Problemy Prochnosti, No. 2, pp. 121–140, March–April, 2008.     

Aptamer based electrochemical sensor system for protein using the generation/collection mode of scanning electrochemical microscope (SECM)

To detect the target molecules, aptamers are currently focused on and the use of aptamers for biosensing is particularly interesting, as aptamers could substitute antibodies in bioanalytical sensing. So this paper describes the novel electrochemical system for protein in sandwich manner by using the aptamers and the scanning electrochemical microscope (SECM). For protein detection, sandwich system is ideal since labeling of the target protein is not necessary. To develop the electrochemical protein sensor system, thrombin was chosen as a target protein since many aptamers for it were already reported and two different aptamers, which recognize different positions of thrombin, were chosen to construct sandwich type sensing system. In order to obtain the electrochemical signal, the glucose oxidase (GOD) used for labeling the detection aptamers since it has large amount of stability in aqueous solution. One aptamer was immobilized onto the gold electrode and the other aptamer for detection was labeled with GOD for generation of the electric signal. Thrombin was detected in sandwich manner with aptamer immobilized onto the gold electrode and the GOD labeled aptamer. The enzymatic signal, generated from glucose addition after the formation of the complex of thrombin, was measured. The generation-collection mode of SECM was used for amperometric H2O2 detection.     

Application of a trochoidal electron monochromator/mass spectrometer system to the study of environmental chemicals.

A trochoidal electron monochromator has been interfaced to a mass spectrometer to perform electron capture negative ion mass spectrometric (ECNIMS) analyses of environmentally relevant chemicals. The kinetic energy of the electron beam can be varied from 0.025 to 30 eV under computer control. No reagent gas is used to moderate the electron energies. An electron energy spread of +/- 0.1 to +/- 0.4 eV full width at half-maximum (fwhm) can readily be obtained at a transmitted current of 2 x 10(-6) A, improving to +/- 0.07 eV at 5 x 10(-7) A. Comparisons of ECNI results from the electron monochromator/mass spectrometer system with those from a standard instrument that uses a moderating gas show similar spectra for heptachlor but not for the s-triazine herbicides, as for example, atrazine. This compound shows numerous adduct ions by standard ECNIMS that are eliminated by using the electron monochromator to generate the mass spectra. Isomeric tetrachlorodibenzo-p-dioxins show distinct differences in the electron energies needed to produce the maximum amount of parent and fragment anions. Multiple resonance states resulting in stable radical anions (M.-) are easily observed for nitrobenzene and for polycyclic aromatic hydrocarbons. Ionic products of dissociative electron capture invariably occur from several resonance states.     

A new alternative representation of impedance data using the derivative of the tangent of the phase angle: Application to the YSZ system and composites

The aim of this work is to propose a new alternative representation of impedance data using the derivative of the tangent of the phase angle, which allows enhanced discrimination between processes with relaxation frequencies that are very close. The new representation allows discrimination between overlapped processes within a factor of 2 in their relaxation frequencies for process with similar strength. Equations for the simplified behaviour of the impedance data have been proposed to obtain all the parameters of the processes involved in the impedance spectrum. This new alternative representation has been applied to bulk and grain boundary responses of YSZ with very satisfactory results. It has also been applied to the qualitative study of impedance data of a CuO composite showing the usefulness of this representation to discriminate different electrode processes. This approach provides an ab initio method of identify the contributing components to an electrochemical impedance spectrum with quite remarkable resolution. It is suggested that if this method is applied to provide starting parameters for non-linear least squares fitting using constant phase elements, then problems due to correlation of parameters and identification of components can be minimised.     

An analytical approach to quantitative effect estimation of operation advisory system based on human cognitive process using the Bayesian belief network

The design of instrumentation and control (I&C) systems for nuclear power plants (NPPs) is rapidly moving towards fully digital I&C systems and is trending towards the introduction of modern computer techniques into the design of advanced main control rooms (MCRs) of NPPs. In the design of advanced MCRs, human–machine interfaces have improved and various types of decision support systems have been developed. It is important to design highly reliable decision support systems in order to adapt them in actual NPPs. In addition, to evaluate decision support systems in order to validate their efficiency is as important as to design highly reliable decision support systems. In this paper, an operation advisory system based on the human cognitive process is evaluated in order to estimate its effect. The Bayesian belief network model is used in the evaluation of the target system, and a model is constructed based on human reliability analysis event trees. In the evaluation results, a target system based on the operator's cognitive process showed better performance compared to independent decision support systems.     

20000m~3/h空分设备氧压机全自动控制系统应用

文章介绍了氧压机全自动控制系统的应用功能 ;详细分析了防喘振调节 ,入口导叶调节等全自动控制的实现。全自动控制系统的投入将操作过程大大简化 ,更好地满足了控制要求。     

The role of the surface roughness on the integrity of thermally generated oxide scales. Application to the Al2O3/MA956 system

This work deals with the effect of the metal roughness on the integrity of thermally generated oxide scales. For illustrative purposes, experimental evidence is shown for the alumina forming MA 956 alloy. The experimental results reveal that scale spallation occurs more readily in scales with rough surfaces than in scales with smooth surfaces, preferentially at the crests of the scale profile. In order to explain this feature, the effect of the roughness of both the gas/scale and scale/metal interfaces on the thermal stress distribution was analyzed by the finite element method. This analysis shows that with increasing roughness a gradient of compression stresses develops in the scale, being the maximum value of stresses located near the gas/scale interface. In general, the higher the roughness the higher the difference between the maximum and minimum values of the stresses. However, the average value of the stress distribution through the scale thickness decreases with increasing surface roughness. The effect of a planar gas/scale and a rough scale/metal interfaces was also modelled. In this case, the stress gradient in the scale was found to monotonically increase with increasing roughness although in a lower extension than when a rough gas/scale interface was also considered. On the basis of the experimental results and the stress distribution analyses a sequence of the scale failure during the cooling stage are proposed for both cases. It is concluded that the stress component that is normal to the interface and the shear stress play a key role on the scale integrity.     

Modelling of a thermal insulation system based on the coldest temperature conditions by using artificial neural networks to determine performance of building for wall types in Turkey

In formation of building external envelope, as two important criteria, climatic data and wall types must be taken into consideration. In the selection of wall type, the thickness of thermal insulation layer (d_i) must be calculated. As a new approach, this study proposes determining the thermal insulation layer by using artificial neural network (ANN) technique. In this technique five different wall types in four different climatic regions in Turkey have been selected. The ANN was trained and tested by using MATLAB toolbox on a personal computer. As ANN input parameters, U_w, T_e,Met, T_e,TSE, R_wt, and q_TSE were used, while d_i was the output parameter. It was found that the maximum mean absolute percentage error (MRE, %) is less than 7.658%. R² (%) for the training data were found ranging about from 99.68 to 99.98 and R² for the testing data varied between 97.55 and 99.96. These results show that ANN model can be used as a reliable modeling method of d_i studies.     

Time-alignment of bidimensional chromatograms in the presence of uncalibrated interferences using parallel factor analysis: Application to multi-component determinations using liquid-chromatography with spectrofluorimetric detection

A new methodology for the alignment of matrix chromatographic data is proposed, based on the decomposition of a three-way array composed of a test and a reference data matrix using a suitably initialized and constrained parallel factor (PARAFAC) model. It allows one to perform matrix alignment when the test data matrix contains unexpected chemical interferences, in contrast to most of the available algorithms. A series of simulated analytical systems is studied, as well as an experimental one, all having calibrated analytes and also potential interferences in the test samples, i.e., requiring the second-order advantage for successful analyte quantitation. The results show that the newly proposed method is able to properly align the different data matrix, restoring the trilinearity which is required to process the calibration and test data with second-order multivariate calibration algorithms such as PARAFAC. Recent models including unfolded partial least-squares regression (U-PLS) and N-dimensional PLS (N-PLS), combined with residual bilinearization (RBL), are also applied to both simulated and experimental data. The latter one corresponds to the determination of the polycyclic aromatic hydrocarbons benzo[b]fluoranthene and benzo[k]fluoranthene in the presence of benzo[j]fluoranthene as interference. The analytical figures of merit provided by the second-order calibration models are compared and discussed.     

Application of the wanklyn model to the BaOBaF2B2O3Y2O3Fe2O3 flux system

Data on the BaOBaF₂ B₂O₃ Y₂O₃ Fe₂O₃ flux system are analyzed in terms of the model recently proposed by Wanklyn, verified thus far for lead- and alkali- based fluxes. The model is found to hold, with the noticeable exception that in this particular case the basic oxide and the corresponding fluoride are not equivalent from the standpoint of phase equilibria: on the contrary, a BaF₂ addition makes “ineffective” a small but definite fraction of the BaO present in the melt.     

Simultaneous determination of the optical indices of an absorbant film and its metallic substrate by statistical analysis of spectroreflectometric data: Application to the oxide/titanium system

A method to compute the optical indices of a thin absorbant film, together with those of its metallic substrate, from a statistical analysis of the reflectance changes with film thickness d of the metal-film system is given. The results are applied to anodic oxide films grown on titanium. The accuracy of the indices of the titanium substrate is shown to be a function of the ratio of the film thickness to the wavelength. By using films with thicknesses ranging between 10 and 2500 Å, the optical indices in a wavelength range 0.25–2.5 μm were obtained. The titanium indices are compared with results recently cited in the literature; the accuracy of our result, for instance in the determination of the bulk plasmon frequency, is demonstrated.