A Simplified Rat Model for Studying Nasal Drug Absorption

Abstract

A simple and rapid rat model for studying nasal drug absorption was developed. In this model, a solution of the test drug, propranolol hydrochloride, was gradually deposited into the nasal cavity of an anesthetized rat through a PE-20 polyethylene catheter connected to a tuberculin syringe via a 30 gauge needle. The extent of drug bioavailability was assessed by measuring propranolol blood levels and the changes in heart rate. For comparative purposes, identical experiments were repeated using the intravenous route of administration, an established rat model requiring surgery, and the proposed model after tracheal cannulation and esophageal li-gation. Although the pharmacokinetic parameters for the various models tested indicated bioavailabilities that were quite similar to that obtained by the intravenous route of administration, the drop in heart rates appeared to be more pronounced with the proposed model than with any of the other two models. In addition to its simplicity, the proposed rat model represents a less stressful and more physiological means of delivering a drug by the nasal route.     

一种简化的船舶辐射噪声源模型

船舶水下辐射噪声在近场具有复杂的空间强度分布,为了准确地分析船舶水下辐射噪声的特性,建立了一个由多极子组成的简化的船舶辐射噪声源模型.在证明了该模型的合理性之后,利用优化算法由船舶目标的不同航次的近场噪声数据反演出简化模型中的参数,并由反演得到的参数反算另一航次的声压值,然后将反算的声压值与理论声压值进行对比.仿真结果表明在船舶辐射噪声的近场,所建立的简化的船舶辐射噪声源模型是有效的.     

非连续增强复合材料应力分析的简化模型

本文建立了非连续增强复合材料应力分析的简化模型,在此基础上引入复变函数理论导出复合材料内部应力大小及分布的解析表达式,并利用计算机进行了数值分析,结果表明,在增强体端部有很大的应力集中。     

A Diffusion Model for Studying the Drug Release from Semisolid Dosage Forms I. Methodology Using Agar Gel as Diffusion Medium

Several ointment bases containing three sulfonamides widely different in their physicochemical properties were evaluated for their drug release properties using agar gel as the drug acceptor phase. The drug release/diffusion model was created by making an empty cylindrical core in the center of agar gel plate which was filled with ointment containing the drugs. The results showed that a linear correlation existed when the amount of drug released from each ointment was plotted against the logarithmic time. The solubility of drugs in the base and partition properties into the agar medium played the major role for the release of drugs. The effect of temperature on the diffusion into the acceptor phase was also recorded.     

A Diffusion Model for Studying the Drug Release from Semisolid Dosage Forms I. Methodology Using Agar Gel as Diffusion Medium

Abstract

Several ointment bases containing three sulfonamides widely different in their physicochemical properties were evaluated for their drug release properties using agar gel as the drug acceptor phase. The drug release/diffusion model was created by making an empty cylindrical core in the center of agar gel plate which was filled with ointment containing the drugs. The results showed that a linear correlation existed when the amount of drug released from each ointment was plotted against the logarithmic time. The solubility of drugs in the base and partition properties into the agar medium played the major role for the release of drugs. The effect of temperature on the diffusion into the acceptor phase was also recorded.     

非均质地基上条形基础动力阻抗函数的简化分析模型

本文在平面应变条件下,给出层状半无限地基动力阻抗函数的简化计算模型。在分析中,假定基础下部只有一定范围内的土体有效地参与波的传播与能量传递,同时略去水平与摇摆振动中的耦合影响。通过数值计算,研究了地基不均匀性以及土料特性的变化对动力阻抗函数的影响。     

A Kohlrausch Type Equation Based on a Simplified Cooperative Model

The differential equation is analysed, with n denoting the relaxing quantity, n = dn/dt(tis time), and a, band sconstants. Equations of this type have previously been shown to describe a large variety of relaxational patterns. Especially interesting is the close relationship with Bose–Einstein (B–E) like distributions and the underlying induction mechanisms. Here, the focus is on the special case of a= 0 which yields a generalised stretched exponential and, for certain variable ranges, the Kohlrausch (KWW) function in its usual form. The relaxation time is shown to depend strongly on the parameters entering the underlying differential equation. Conditions for constant are given.     

瓦楞纸板基于抗弯刚度的一种简化模型

基于等效抗弯刚度原理,对瓦楞纸板进行了简化,得到了瓦楞纸板的简化模型——等效板,并利用An-sys Workbench有限元软件对等效板有限元模型进行了屈曲分析,最后通过试验进行了验证。结果表明,通过抗弯刚度得到瓦楞纸板简化模型的方法简单可行。     

A New Simplified Local Density Model for Adsorption of Pure Gases and Binary Mixtures

Adsorption modeling is an important tool for process simulation and design. Many theoretical models have been developed to describe adsorption data for pure and multicomponent gases. The simplified local density (SLD) approach is a thermodynamic model that can be used with any equation of state and offers some predictive capability with adjustable parameters for modeling of slit-shaped pores. In previous studies, the SLD model has been utilized with the Lennard–Jones potential function for modeling of fluid–solid interactions. In this article, we have focused on application of the Sutherland potential function in an SLD–Peng–Robinson model. The advantages and disadvantages of using the new potential function for adsorption of methane, ethane, carbon dioxide, nitrogen, and three binary mixtures on two types of activated carbon are illustrated. The results have been compared with previous models. It is shown that the new SLD model can correlate adsorption data for different pressures and temperatures with minimum error.     

Application of the Isolated Perfused Rat Kidney Model to Assess Gender Effects on Drug Excretion

ABSTRACT

Purpose. To study the effect of gender on the renal disposition of two organic anions, p-aminohippuric acid (PAH) and furosemide (FSM) in the isolated perfused rat kidney (IPK). Methods. IPK experiments (3–4 per treatment group) were conducted using kidneys from male and female Sprague Dawley rats. PAH was administered as a continuous infusion (with loading dose, targeted steady-state concentration 10 ug/mL). FSM was added as a bolus dose (2.65 mg, targeted concentration 33 ug/mL). Urine was collected in 10-min. intervals and perfusate was sampled at the midpoint of each collection period. Control (drug naïve) perfusions were performed for both genders. PAH and FSM were measured by HPLC. Kidney viability (GFR [estimated using inulin clearance], sodium reabsorption, glucose reabsorption) was monitored continuously during each perfusion experiment (2-h duration). Results. Good kidney function was maintained across all study groups, and lower GFR estimates in female kidneys were due to differences in kidney weight. For PAH, kidney weight corrected renal clearance (0.88 ± 0.37 mL/min/g vs. 0.59 ± 0.19 mL/min/g) and excretion ratio (3.8 ± 1.7 vs. 2.2 ± 0.72) were significantly higher in male kidneys. For FSM, renal clearance was significantly lower in female (0.10 ± 0.05 mL/min/g) compared to male kidneys (0.15 ± 0.07 mL/min/g). Mass balance analysis showed that FSM cumulative urinary excretion was significantly higher and kidney accumulation was significantly lower in experiments with male kidneys. Conclusions. The study demonstrates that the IPK is a useful model to assess gender effects on renal drug disposition. The renal excretion of organic anions is reduced in female rats, possibly due to gender differences in expression and/or activity of membrane transporters (both basolateral and luminal) in the kidney.     

Simplified Model for the Critical Thermal-Conductivity Enhancement in Molecular Fluids

This paper reviews the available information for the thermal-conductivity enhancement. This enhancement can be represented by a simplified solution of the mode-coupling theory of critical dynamics with two critical amplitudes and one cutoff wave number as fluid-specific parameters. Using corresponding states, these fluid-specific parameters are correlated in terms of their dependence on the acentric factor. A universal representation of the critical enhancement of the thermal conductivity for a large number of molecular fluids is presented.     

全年干球温度简化分布模型及其应用

通过对全年干球温度概率分布的双波简化模型中分布参数物理意义的分析,在考虑冬夏季方差不相等的条件下提出了确定分布参数的方法,建立了全年干球温度的截尾正态分布简化模型.该模型的应用更为方便和精确,可方便地用来估算暖通空调建筑物的能耗、计算度日数和温频,可供暖通空调系统的设计、运行作参考.     

一种氨水水平降膜吸收传热模型

在Navier-Stokes方程的基础上,提出一种新的氨水降膜吸收传热模型,通过对降膜过程中的液膜流动特性进行了一维变换,采用Grank-Nicholson方法对降膜特性进行求解,然后根据实验验证了理论模型的仿真结果,实验数据和仿真数据的误差在17%以内,并根据实验数据拟合出了传热系数公式,确定了不同管径下液膜的最大体积流量。     

A Simplified Model to Estimate the Size Distribution Change of Polydispersed Aerosol for Cyclone Separator

ABSTRACT

Although the air-lift pump has been superseded by submersible pumps in raising water from wells and mines, it still provides an attractive means of lifting abrasive slurries because, unlike mechanical pumps, it has no moving parts to wear. However, current design of air-lift pumps must rely on empirical equations, or, at best, incremental computer solutions. Design is complicated by the fact that relative velocities of the phases change over the whole pump length. A new design equation is developed to predict the lift of an air-lift pump, given the flowrates of air, liquid and solid in the pump, and the dimensions of the air-lift tube. The new equation is baaed on well-established multiphase flow theory, and offers significant advantages over current design techniques. In combination with an equation for the overall pump efficiency, the new equation provides a method for optimizing the design parameters for the air-lift pump.     

Nasal Absorption of the Calcium Antagonist Nicardipine in Rats and Rhesus Monkeys

Nicardipine hydrochloride, a highly potent calcium entry channel blocker was administered intranasally to rats and rhesus monkeys. The Intranasal absorption of nicardipine in rats was studied with aqueous vehicles containing 0.1 M citrate buffer pH 3.5, 0.01 M acetate/propylene glycol (90:10 W/W) pH = 5.0, and a similar acetate/propylene glycol system containing sodium taurocholate. Peak plasma levels were found to occur 30 minutes after an Intranasal dose of 1.0 mg/kg, and the fraction absorbed using each of the vehicles described above was determined to be 0.85, 0.54, and 0.82 that of an equivalent Intravenous dose. These Initial screening studies were extended Into a monkey model system, with a similar group of formulations. The results obtained in the monkey were qualitatively similar to the data generated in the rat model with regard to rapid attainment of peak plasma levels and subsequent elimination from the plasma. The major difference between the two animal models studied was the significantly lower systemic availability observed in the monkey.     

Nasal Absorption of the Calcium Antagonist Nicardipine in Rats and Rhesus Monkeys

Abstract

Nicardipine hydrochloride, a highly potent calcium entry channel blocker was administered intranasally to rats and rhesus monkeys. The Intranasal absorption of nicardipine in rats was studied with aqueous vehicles containing 0.1 M citrate buffer pH 3.5, 0.01 M acetate/propylene glycol (90:10 W/W) pH = 5.0, and a similar acetate/propylene glycol system containing sodium taurocholate. Peak plasma levels were found to occur 30 minutes after an Intranasal dose of 1.0 mg/kg, and the fraction absorbed using each of the vehicles described above was determined to be 0.85, 0.54, and 0.82 that of an equivalent Intravenous dose. These Initial screening studies were extended Into a monkey model system, with a similar group of formulations. The results obtained in the monkey were qualitatively similar to the data generated in the rat model with regard to rapid attainment of peak plasma levels and subsequent elimination from the plasma. The major difference between the two animal models studied was the significantly lower systemic availability observed in the monkey.