青霉素亚砜结晶生长与成核动力学

第 65 卷 第 1 期 2014 年 1 月
化 工 学 报 CIESC Journal
Vol.65 No.1 January · 182·
青霉素亚砜结晶生长与成核动力学
井丁丁 1,2，张美景 2，王永莉 2，王静康 2
(1 天大方圆工业结晶科技有限公司，天津 300457；2 天津大学化工学院，化学工程联合国家重点实验室，天津 300072) 摘要：利用 Mydlarz 和 Jones 模型 (MJ2)，对乙酸丁酯中青霉素亚砜的成核与生长动力学进行研究。通过矩量法 对 MJ2 模型进行处理后，利用晶体产品的粒度分布计算得到青霉素亚砜的生长速率与成核速率，然后利用最小二 乘法拟合回归求解出成核与生长动力学方程参数。通过实验设计考察了过饱和度、温度与搅拌速度对青霉素亚砜 晶体成核和生长过程的影响。研究表明青霉素亚砜晶体生长速率随过饱和度比的增加呈现指数型增长，确定青霉 素亚砜晶体生长属于晶体表面生长控制过程。 由于高速搅拌会增加青霉素亚砜晶体的破碎， 促进了二次成核过程， 随着搅拌速度的增加，晶体生长速率出现小幅下滑，而成核速率则明显升高。青霉素亚砜成核与生长动力学研究 将有助于工业生产过程优化。 关键词：结晶；动力学；矩量法；成核； 晶体生长；青霉素亚砜 DOI：10.3969/j.issn.0438-1157.2014.01.023 中图分类号：TQ 463+.3 文献标志码：A 文章编号：0438—1157（2014）01—0182—08
V ΔLΔn = (Qi ni ΔLΔt + Vn1G2 Δt ) − (QnΔLΔt + Vn2G2Δt ) +
V ( B − D ) Δ LΔ t
(2)
1
1.1
Theory
Population balance Crystal size distribution is one of the most important characters of crystal product and related to crystal nucleation rate and residence time in crystallization. Crystal nucleation kinetics of certain system under certain conditions can be obtained with the analysis on crystal size distribution, so that some approaches could be applied to improve the process of crystallization. Population density is the number of crystals per unit volume of crystal magma with the crystal size L−1. The expression range of ΔL, with unit of #· μm−1· of population density is
Abstract：The crystal growth and nucleation kinetics of penicillin sulfoxide in butyl acetate were studied with Mydlarz & Jones model, which fits the experimental values best. After the model was treated by moment transformation, the crystal growth and nucleation rates were calculated from the crystal size distribution. The parameters in crystallization kinetic functions were obtained with the least square method. The effects of supersaturation ratio, temperature and agitator speed were examined. In conclusion, the crystal growth of penicillin sulfoxide is controlled by surface growth because the growth rate increases greatly with the increase of supersaturation ratio. High agitator speed results in the breakage of penicillin sulfoxide crystals and improves the secondary nucleation. As a result, crystal growth rate decreases and nucleation rate increases with the increase of agitator speed. The study on crystal growth and nucleation kinetics will be beneficial to the industrial production of penicillin sulfoxide. Key words: crystallization; kinetics; moment transformation；nucleation; crystal growth; penicillin sulfoxide
Crystal growth and nucleation kinetics of penicillin sulfoxide
JING Dingding1,2, ZHANG Meijing2, WANG Yongli2, WANG Jingkang2
（1Tianda Fangyuan Industrialization Crystallization Technology Co.Ltd., Tianjin 300457, China; 2State Key Laboratory of Chemical Engineering，School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072，China）
Received date：2013-06-17. Corresponding author: Prof. WANG Jingkang, jkwang@ Foundation item: suppence Foundation of China(20836005).
density of feed ni , volumetric flow rate of discharge Q, and mean population density of discharge n . Let G be the crystal growth rate. Within time Δt, the cumulant of crystal population is V ΔLΔn , the population of crystal entering the crystallizer is Qi ni ΔLΔt , the population of crystal from the crystallizer is QnΔLΔt , the population of crystal grown in the range is Vn1G2 Δ t , the population of crystal grown outside the range is Vn2 G2 Δt , the population of the new generation is VBΔLΔt , and the population of disappeared crystal is VDΔLΔt . The relation can be expressed as
ΔL → 0
The crystallizer used most frequently in industry is mixed suspension mixed product removal (MSMPR) crystallizer. The concentration of the system is well-distributed, in which the suspension density and crystal size distribution are considered uniform. Both feed and discharge have the same crystal size distribution and suspension density. This assumption can simplify the crystallizer design greatly. In an MSMPR crystallizer, the breakage is little, so birth rate B = 0 and death rate D = 0. The feed does not contain crystalline, then ni = 0. In an infinitesimal time Δt, ΔL is close to 0. For a process in steady state, ∂n = 0 , so the population balance is simplified to ∂t
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井丁丁等：青霉素亚砜结晶生长与成核动力学
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kinetic study is the basic for designing crystallization reactor and guiding industrial production[1]. Penicillin sulfoxide[2-4] is used to produce 7phenylacetamidodesacetoxy-cephalosporin acid,which is the precursor of 7-amino-3- desacetoxycephalosporanic acid, by catalytic ring-enlargement reaction[5-9]. The crystal of penicillin sulfoxide grown from butyl acetate displays a bi-pyramidal morphology. Penicillin sulfoxide with different morphology presents different physical and chemical properties such as dissolution rate, melting point, density, hardness and appearance [10]. The crystallization process determines the quality of penicillin sulfoxide, such as crystal size distribution and purity, so researches on crystallization kinetics are necessary. The technology of preparing penicillin sulfoxide is advanced and a patent is applied. The new process has following advantages: simpler process, higher purity, better crystal size distribution, and less waste water. For its industrial production, its crystallization kinetics is investigated in this study.