【作者】 苏保卫；

【导师】 王世昌； 王志；

【作者基本信息】 天津大学 ， 化学工程， 2004， 博士

【摘要】 制药行业中大量使用的有机溶剂造成了较严重的环境污染;另一方面,药物生产中广泛采用的真空蒸发浓缩工艺,不仅能耗较高,产品纯度低,且易破坏抗菌活性,亟待开发新的分离浓缩工艺。本文即以此为工业背景,以克林霉素磷酸酯(Clindamycin Phosphate,以下简称 CLP)树脂解吸液(乙醇水溶液)作为研究对象,筛选了适合于该溶液分离浓缩的纳滤膜,进行了纳滤浓缩实验研究,系统研究了该溶液纳滤分离过程中的影响因素、传递特性与膜污染现象,建立了工业试验装置并成功运行。 首先考察了乙醇水溶液的通量和纯水通量的差异,结果表明乙醇水溶液的通量均小于纯水通量。然后通过实验,筛选出适合 CLP 乙醇水溶液浓缩分离的纳滤膜:DL 和 DK 膜,两种膜对 CLP 的表观截留率均在 99%以上,且可保持较高的通量。采用 DL 膜,系统地考察了压力、温度、切向流速和进料浓度等对 CLP乙醇水溶液纳滤膜过程的影响,并筛选出合适的操作条件。 对本实验体系,适宜的操作压力为 1.2~1.6MPa,温度为 40~50?C。切向流速对纳滤膜的通量有较大影响,宜采用较高的切向流速;进料浓度较高时,易形成膜面结晶,从而造成通量的较快下降。 纳滤浓缩实验将 CLP 乙醇水溶液由 40g/L 浓缩至 90g/L,随浓缩过程的进行,通量呈逐渐下降趋势,透过液浓度小于 0.5g/L,截留率保持在 99%以上。在此基础上,采用 DL2540 膜元件,在生产现场进行了实际料液的浓缩实验,截留率达到 99%以上。 膜样品在 65?C 的乙醇水溶液中浸泡 420 小时后,对 CLP 的截留率仍可达到96%,表现出了很好的耐溶剂性能。 对膜外传递和膜内传递进行了理论探索,建立了描述膜外传递的圆形膜池平行板间错流过滤模型—改进的 WZY 模型,实验结果表明,在进料浓度为 60g/L以下时,本文模型与实验值符合较好,而当进料浓度高于 60g/L 时,实验值比预测值略低。利用该模型对 CLP 乙醇水溶液的纳滤分离过程进行了较全面的预测,考察了压力、温度、切向流速、膜池通道的长度与缝宽等因素对过程的影响。在其它条件不变的情况下,流速越大,进料浓度越高,流道越窄、越短,浓差极化程度就越小,从而就越有利于纳滤过程;而较低的压差和较低的温度有利于保持较低的浓差极化程度。建立了描述膜内传递的 ESHPS 模型,并用来估算纳滤膜的结构参数,估算的 DL 纳滤膜的平均孔半径约为 0.6nm。对膜中传递速率的分析表明,本实验体系中,扩散传递与对流传递相比,前者起主导作用。 XPS 测试结果显示,在较低的进料浓度下膜面有微量的 CLP 存在,进一步 I<WP=4>分析表明膜与 CLP 的相互作用为较弱的物理吸附。SEM 观察结果表明,在较高的进料浓度(大于 60g/L)下,CLP 在膜面上易形成结晶。考虑到处理的是药物体系,我们采用了气液两相流冲洗和热水冲洗两种膜清洗方案,前者对于低浓度进料比较有效,后者对高浓度进料产生的膜面结晶的清洗效果较好,清洗后通量完全恢复。建立了 CLP 纳滤浓缩的工业试验装置并成功运行,膜元件为 DL8040。为期半年的运行结果表明,纳滤膜的性能稳定,对 CLP 的截留率可达到 98%。进行了 CLP 树脂解吸液纳滤浓缩工程项目的经济分析,结果表明该项目具有很好的经济效益,且社会效益和环境效益显著。更多还原

【Abstract】 Pharmaceuticals are indispensable for human being. However, large amounts oforganic solvents are used for the production of pharmaceuticals, some of them may berejected into air and water, causing severely environmental pollution. Meanwhile, theenergy consumption of vacuum evaporation utlized to concentrate the dilutepharmaceutical solution is high. Furthermore, owing to the heat sensitivity, thepharmaceuticals may be damaged to some extent by vacuum evaporation, thusresulting in a low product purity and the destruction of antibacterial activity.Therefore it is urgent to develop a new separation and concentration technology. Most pharmaceutical molecular weights are smaller than 1000 Dalton, which liein the nanofiltration molecular weight cut-off range. It is promising to utilizenanofiltration for pharmaceutical organic solution or aqueous organic solutionseparation and concentration. However, the application in organic solution or aqueousorganic solution is relatively scarce. Based on the above background, the feasibility of NF concentration of thepharmaceutical aqueous organic solution was carried out using clindamycin phosphate(CLP) ethanol aqueous solution as model solution. The most suitable membrane wasscreened out and the effects of various factors on the performance of NF membranewere investigated, the characteristics of mass transfer and the mechanism and cure ofmembrane fouling were also studied. The difference between the permeate flux of ethanol-water mixture and the purewater was experimentally studied, the result shows that the former is quite small thanthe latter. And then DL and DK membrane, which are screened out experimentally,have high rejection of more than 99% while remaining a high permeate flux, thepermeate flux of DL is even higher than DK. Using DL membrane, the effects ofpressure, temperature, bulk velocity in the channel, and the concentration of the feedsolution on the separtion process were experimentally investigated. The suitableoperating pressure range is in the range of 1.2 to 1.6MPa, the suitable temperaturerange is 40~50?C. Bulk velocity has much effect on the performance of the membrane.Higher Bulk velocity is preferred in the nanofiltration process. Feed concentrationalso has great effect on the performance of DL membrane. At higher feedconcentration, CLP may form surface crystallization, resulting in the decrease of thepermeate flux. III<WP=6>The anti-solvent property of DL membrane was investigated. DL can withstandethanol-water mixture at temperature higher than 65?C, while remaining a rejection of96%. The nanofiltration concentration of CLP aqueous ethanol solution by DLmembrane was investigated, the solution was concentrated from 40g/L up to 90 g/L.With the increase of the concentration of the pharmaceutical, the permeate fluxdecreases gradually. However, the rejection is higher than 99%. the permeateconcentration remains lower than 0.5g/L, which was suitable for serving as desorptingsolvent. Pilot scale experiment was performed in the pharmaceutical factory with DL2540 membrane to concentrate CLP resin desorption solution, the rejection of CLPwas higher than 99%. The mass transfer phenomena outside and inside the membrane wereinvestigated. A parallel plate crossflow filtration model -modified WZY model, wasestablished. The permeate flux predicted by the modified WZY model agrees with theexperimental value quite well at concentration lower than 60g/L. However, itoverestimated the permeate flux at concentration higher than 60g/L which is due tothe surface crystalization. The nanofiltration separation process of CLP aqueousethanol solution was predicted using the modified WZY model, and the effects ofpressure, temperature, bulk velocity, and length and width of the channel on theprocess were predicted. Higher feed flow rate and feed concentration of CLP,narrower membrane cell channel and shorter channel length, will cause更多还原