微滤法精制何首乌水提液的研究

目的对无机陶瓷膜微滤技术精制何首乌水提液的效果进行初步评价。方法用孔径为0．2μm的无机陶瓷膜对何首乌水提液进行微滤，对提取液微滤前后在性状、总固体、二苯乙烯苷含量、膜通量等方面的变化进行对比分析。结果何首乌水提液微滤前为浑浊溶液，微滤后为澄清溶液，透过液固体去除率为67．9％、二苯乙烯苷含量是水提取液中的2．04倍，膜通量的衰减具有一定的规律性。结论无机陶瓷膜微滤技术对何首乌提取液有较好的精制效果。     

超滤技术分离中药有效成分的实验研究

通过实验，研究膜分离主要影响因素与提取物中有效成分的转移率、药液的膜通量和干膏（固体物）降低率3个指标的关系，探讨膜分离技术分离中草药有效成分的先进性、适用性与经济性。以提取物中有效成分的转移率、药液的膜通量和干膏（固体物）降低率3个考察指标作为评价的标准，对中药苦玄参、黄芩、黄柏水提液进行超滤实验。结果表明，超滤技术不仅能除去大部分杂质，而且能较为有效地保留有效成分。在实验中并对膜孔径、操作温度、料液浓度和操作压力等主要影响因素进行了研究。     

陶瓷膜微滤复方板蓝根利咽颗粒水提液的膜清洗工艺优选

目的：优选0．2μm Al2 O3陶瓷膜微滤复方板蓝根利咽颗粒水提液的膜清洗工艺。方法以膜通量恢复率为指标,优选被污染陶瓷膜的清洗剂、清洗剂浓度、清洗温度、清洗时间等清洗工艺参数。结果陶瓷膜微滤复方板蓝根利咽颗粒水提液10min后,药液膜通量已达稳态膜通量,衰减为初始水通量1740L／（m2? h）的14％～22％,即244L／（m2? h）～383L／（m2? h）,说明陶瓷膜已被污染;该体系陶瓷膜的最优清洗工艺为：复方板蓝根利咽颗粒水提液经陶瓷膜微滤结束后,分别用10kg 室温饮用水在进口压力0．2MPa、膜面流速5m／s 的条件下清洗3次,1次1min,再用10kg 60℃0．5％次氯酸钠溶液在相同微滤条件下清洗30min,膜通量恢复率可达90％以上。结论优选的陶瓷膜清洗工艺稳定、简便、快速,为复方板蓝根利咽颗粒水提液大批量陶瓷膜精制清洗工艺提供依据。     

无机陶瓷膜超滤精制金茵利胆胶囊的工艺研究

目的 考察氧化铝无机陶瓷膜精制金茵利胆胶囊水提液的最佳膜孔径及最优操作条件。方法 以金茵利胆胶囊水提液为研究对象，采用单因素试验法，以绿原酸转移率、膜通量等为评价指标，优化在不同药液浓度及不同操作压力条件下水提液的精制效果。结果 针对本体系，选用孔径为0.2 μm的无机陶瓷膜，药液浓度0.05 g·mL^-1，操作压力0.6 MPa条件下，膜通量和绿原酸的转移率都较高。结论 无机陶瓷膜在精制金茵利胆胶囊中药水提液过程中具有很好的适用性，为后期的工业化生产奠定了理论基础。     

超滤法纯化栀子中栀子苷工艺研究

目的探讨采用超滤膜法分离技术纯化栀子中栀子苷的工艺。方法以平均膜通量、栀子苷膜透过率和干膏中栀子苷的质量分数为评价指标进行正交实验设计，对料液的浓度(A)、操作压力（B）、料液温度（C）、料液流速（D）四个因素进行优选。结果优选工艺为A2B1C3D3，即料液浓度为生药量0.12 g·mL 1，操作压力为0.15 MPa，料液温度为40 ℃，料液流速为15 mL·min 1时纯化效果最好。结论所选择的膜分离技术纯化栀子中栀子苷的工艺操作简单可靠，纯化效率高。     

多效膜蒸馏技术在中药提取液浓缩中的应用研究

利用多效膜蒸馏技术对中药提取液进行浓缩.考察了进料温度T1、料液加热温度T3和料液流量对膜通量和造水比的影响.结果显示T1升高时膜通量下降而造水比升高;T3升高时膜通量和造水比随之增加;料液流速增加会使膜通量增加,而造水比随之降低;随着浓缩的进行,膜通量和造水比逐渐降低.通过30d连续操作,发现膜组件的操作性能保持稳定.说明使用多效膜蒸馏可将中药提取液浓缩16倍以上,操作温度为70℃时,膜通量可达3L·m-2.h-1,造水比可达7.     

葡萄糖氧化酶电极中酶固定化的研究

研究了以丝纤维为载体，三聚氯氰为交联剂固定化葡萄糖氧化酶膜的方法和条件。实验表明，用二氧六环－二甲苯（质量比１１）为三聚氯氰的溶剂，固定化酶膜效果较好。酶的偶联条件以温度２５℃、ｐＨ＝９、酶液浓度４ｍｇ／ｍｌ为最佳，此时固定化酶膜稳定性好，反复使用３０次酶膜活性保留９０％以上，贮存在离子强度较高的溶液中，酶膜的半衰期为４０～５０周。     

液膜技术分离回收发酵废液中土霉素的试验研究

在萃取的基础上，进行了乳状液膜分离萃取发酵废液中土霉素的试验研究。液膜体系组成为：氯代十六烷基吡啶(PCC)为载体，Span—80为表面活性剂，异辛醇为助溶剂，煤油为稀释剂，盐酸水溶液为膜内相。通过试验考察了液膜组成、膜内比(Roi)、表面活性剂用量、内相HCl浓度、萃取搅拌速度、外水相pH、以及乳水比(Rew)和萃取时间等因素对萃取率的影响，找出了一个较为适宜的液膜组成和萃取操作的工艺条件，对发酵废液中土霉素的萃取率达到61．33％。     

重楼乙醇提取液的微滤过程

重楼乙醇提取液可用陶瓷微滤膜处理.考察了不同材料及孔径的膜分离性能,以及操作压力、料液浓度等因素对微滤的影响.并针对污染体系的特性,比较各种膜清洗剂的清洗效果,结果显示0.2μm的ZrO2膜较适合.操作压力、流速和反冲方法均显著影响膜通量.     

乳状液膜法提取青霉素及亮氨酸时溶胀现象的研究

研究了用乳状液膜法提取青霉素及亮氨酸时膜相添加剂、内外相浓度梯度、载体、搅拌速率及表面活性剂浓度对液膜溶胀的影响。结果表明 :液膜溶胀中渗透溶胀占主要地位 ;渗透溶胀随载体浓度的增大而增大 ;搅拌速率的增大对夹带溶胀的影响小 ,但可以增大渗透溶胀。     

Study of protein adsorption effects on crossflow filtration using BSA and milk protein

Three membrane materials were tested under similar conditions to determine the effects of membrane material on the performance and cleanability of the filters. The membrane materials investigated were stabilized cellulose (Hydrosart, Sartorius Corporation), cellulose triacetate, and polyethersulfone; all having a 10 kilodalton molecular weight cutoff. Stabilized cellulose is a cellulose-based membrane material, modified for low non-specific protein adsorption combined with high pH-resistance. When analyzing the data, three phenomena were considered: adsorption of protein to the membrane, gel layer formation, and osmotic pressure due to concentration polarization. Throughout these studies, the effects of a gel layer and the osmotic pressure were approximately equivalent in all cassettes. However, the stabilized cellulose was resistant to protein adsorption while the other two membranes exhibited significant decreases in permeate flux due to adsorption. Using a 0.2% BSA (MW = 67,000 kD) solution with a crossflow rate of 5 L/min and transmembrane pressure of 35 psi, the permeate flux through the stabilized cellulose membrane was 3% lower than the baseline saline flux, whereas the cellulose triacetate and polyethersulfone membranes lost 33% and 60% of baseline flux, respectively. The decrease in flux occurring in the latter two membranes is due to adsorption. Another study evaluated adsorption by alternating between crossflow and static operation. After three cycles, the stabilized cellulose maintained the original crossflow flux level. The polyethersulfone lost cumulatively 17% of its crossflow flux after three cycles and the cellulose triacetate lost 13%. The stabilized cellulose and polyethersulfone membranes were also evaluated using a milk solution. The results indicate that the stabilized cellulose is not susceptible to adsorption of any of the milk components while the polyethersulfone permeate flux was limited by adsorption. The saline flux of the stabilized cellulose immediately after testing with the milk solution was 3% lower than the baseline flux, while the polyethersulfone membrane saline flux was 81% lower. The results consistently indicated that, unlike the cellulose triacetate and polyethersulfone membranes, the stabilized cellulose membrane was not subject to adsorption.     

膜组合技术浓缩辅羧酶

选用高抗污染聚偏氟乙烯(PVDF)超滤膜与醋酸纤维素(CA)反渗透膜相结合的技术浓缩辅羧酶,考察了膜品种的选择、浓缩倍数与通量的关系及膜通量的可恢复性等因素,确定了优化的膜组合技术,可省去一道活性炭吸附工序.由于膜工艺去除了97%的水分,使辅羧酶浓度由初始的0.25%提高到9.4%,降低了成本,缩短了生产周期.     

Effects of concentration boundary layers in a transport of electrolyte solutions through horizontal mounted polymeric membrane

The results of experiment of diffusive transmembrane transport in a single-membrane osmotic-diffusive electrochemical cell were presented. In all experiments one of the vessels was filed with pure water, and the second one--with aqueous potassium chloride solution in aqueous ammonia solutions of constant concentration. The flux of potassium chloride was assigned according to the following measure procedure. In a first step we assigned the time dependence of potassium chloride flux in conditions of uniform mechanically stirred solution with speed of 500 rpm. In a second step those characteristics were assigned in conditions of mechanically unstirred solution. Each experiment was made for two configurations of gravitational membrane system: (i) with the water in a vessel above the membrane and solution below it (configuration A) (ii) with the solution in a vessel above the membrane and water below it (configuration B). Taking under the consideration the values of potassium chloride flux in steady state for different solution concentration of the same substances and the same configurations of membrane system, the dependencies of potassium chloride flux from the solution concentration differences were made appropriately. On the base of those experiments the solute flux concentration boundary layers effects (jCBLE) were counted. Moreover it was shown that single-membrane osmotic-diffusive electrochemical cell has rectifier and amplifying of diffusive flow features. The coefficients, appropriately, of asymmetry and amplification of diffusive flux are the measurements of those features.     

A model for alcohol-enhanced permeation through polydimethylsiloxane membranes

In this study the influence of paraben concentration on flux from solution in 1-propanol through polydimethylsiloxane membranes was investigated. Alcohol was sorbed by the polymer membrane leading to changes in membrane dimensions and increased membrane capacity to contain paraben (partition coefficient). Diffusion coefficients were not significantly influenced by alcohol sorption. Flux was increased 5-30 fold over nonimbibed donors such as water and polyols. An increase in paraben concentration reduced alcohol activity, its uptake by the membrane, and consequently the partition coefficient of paraben. As a result, flux increased with paraben concentration, reached a peak, and then declined. Maximal membrane concentration involves a trade-off between alcohol-membrane interaction (solvent activity) and paraben concentration, and occurred at paraben concentrations in the range of 1.3 to 1.4 mmol/g. At equimolar concentrations, flux was highest for methylparaben and declined as the series was ascended. Differences in flux between parabens at a specified molar concentration were due only to differences in diffusivity.     

Effect of the Tubing Material Used in Peristaltic Pumping in Tangential Flow Filtration Processes of Biopharmaceutics on Particle Formation and Flux

Tangential flow filtration (TFF) is a central step in manufacturing of biopharmaceutics. Membrane clogging leads to decreased permeate flux, longer process time and potentially complete failure of the process. The effect of peristaltic pumping with tubings made of three different materials on protein particle formation during TFF was monitored via micro flow imaging, turbidity and photo documentation. At low protein concentrations, pumping with a membrane pump resulted in a stable flux with low protein particle concentration. Using a peristaltic pump led to markedly higher protein particle formation dependent on tubing type. With increasing protein particle formation propensity of the tubing, the permeate flux rate became lower and the process took longer. The protein particles formed in the pump were captured in the cassette and accumulated on the membrane leading to blocking. Using tubing with a hydrophilic copolymer modification counteracted membrane clogging and flux decrease by reducing protein particle formation. In ultrafiltration mode the permeate flux decrease was governed by the viscosity increase rather than by the protein aggregation; but using modified tubing is still beneficial due to a lower particle burden of the product. In summary, using tubing material for peristaltic pumping in TFF processes which leads a less protein particle formation, especially tubing material with hydrophilic modification, is highly beneficial for membrane flux and particle burden of the product.     

Time evolution of NaCl flux through the microbial cellulose membrane with concentration polarization

The method of solute permeability coefficient and solute fluxes appointment for the membrane, based on monitoring of changes of conductivity of electrolyte solutions was presented. It was stated that during mechanical stirring of solutions the coefficient of NaCl permeability for microbial cellulose membrane (Biofill) did not depend on configuration of the membrane system and concentrations of solutions. Time characteristics of NaCl flux through the membrane Biofill oriented in horizontal plane were measured and modeled. The changes of NaCl fluxes through the membrane Biofill caused by concentration boundary layers build up on both sides of the membrane depended on NaCl concentrations and configuration of the membrane system. The differences between fluxes in different configurations of the membrane system were observed after time depended on initial concentrations in chambers. After that time, for configuration with solution with higher density over the membrane (configuration B) the NaCl flux through the membrane was greater than for configuration with solution with lower density over the membrane (configuration A). Besides it was stated that the coefficient of concentration polarization for configuration B was higher than for configuration A for all studied NaCl concentrations. Increase of mean concentration in the membrane at the initial moment caused increase (for configuration B) and lack of changes (for configuration A) of concentration polarization coefficient in the steady state of the membrane system. The interpretation of experimental results was made on the basis of Kedem-Katchalsky equations for the membrane system.     

Streaming gravity-diffusive effect for a series of two flat polymeric membranes oriented horizontally

In this paper the results of study flux gravidiffusive effect for a double-membrane osmotic-diffusive cell, in which series of two (Ml and M(r)), microporous and symmetrical flat polymeric membranes (Nephrophane and Cellulose IMP-1). These membranes separate three compartments (l, m, r) containing the heterogeneous and binary (aqueous glucose or ethanol solutions) or ternary (glucose solutions in 0.75 mole.l-1 aqueous ethanol solution or ethanol solutions in 0.1 mole.l-1 aqueous glucose solution) non-ionic solutions. The solution concentrations fulfil the condition Ckl > Ckm > Ckr. The inter-membrane compartment (m) consists of the infinitesimal layer of solution. The volume of compartment m and external compartment (l and r) fulfill the conditions Vm-->0 and Vl = Vr-->infinity respectively. The study of flux gravidiffusive effect for configurations A and B of the double-membrane osmotic-diffusive cell were elaborated. In configuration A solution was placed in compartment below membrane M(r) and water above membrane Ml. In configuration B solution was placed in compartment above membrane Ml and water below membrane Ml. These results are interpreted in terms of the convective instability that increases the diffusive permeability coefficients of complexes: concentration boundary layers/membrane Ml or M(r)/concentration boundary layer.     

Gravitational effects in the passive osmotic flows across polymeric membrane of electrolytic solutions

Results of experimental study of volume flux in one-membrane system were presented. This system contains horizontal, microporous and symmetrical flat polymeric membrane (Nephrophan), which separate water and electrolyte solution. As binary solutions, aqueous ammonia solutions, which density is lower than water density, were used. As ternary solutions the ammonia with KC1 (0.1 or 0.2 mole.l-1) in aqueous solution were used. The density of ternary solutions was lower, higher or the same as water density. Two configurations of membrane system (A and B) in gravitational field were studied. In configuration A, water was in compartment over the membrane and the solution was under the membrane. In configuration B the succession was reverse. The thermodynamic model of flux graviosmotic effect was elaborated, and the calculations of this effect were performed for A and B configurations of one membrane system. The experimental results are interpreted in terms of gravitational instability that reduces concentration boundary layer dimensions and increases the diffusion permeability coefficient value of the complex: boundary layer/membrane/boundary layer.     

Enhancements and Limits in Drug Membrane Transport Using Supersaturated Solutions of Poorly Water Soluble Drugs

Amorphous solid dispersions (ASDs) give rise to supersaturated solutions (solution concentration greater than equilibrium crystalline solubility). We have recently found that supersaturating dosage forms can exhibit the phenomenon of liquid–liquid phase separation (LLPS). Thus, the high supersaturation generated by dissolving ASDs can lead to a two-phase system wherein one phase is an initially nanodimensioned and drug-rich phase and the other is a drug-lean continuous aqueous phase. Herein, the membrane transport of supersaturated solutions, at concentrations above and below the LLPS concentration has been evaluated using a side-by-side diffusion cell. Measurements of solution concentration with time in the receiver cell yield the flux, which reflects the solute thermodynamic activity in the donor cell. As the nominal concentration of solute in the donor cell increases, a linear increase in flux was observed up to the concentration where LLPS occurred. Thereafter, the flux remained essentially constant. Both nifedipine and felodipine solutions exhibit such behavior as long as crystallization is absent. This suggests that there is an upper limit in passive membrane transport that is dictated by the LLPS concentration. These results have several important implications for drug delivery, especially for poorly soluble compounds requiring enabling formulation technologies. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:2736–2748, 2014