丁烯氟虫腈微胶囊的制备及其性能研究

发布时间：2018-03-22 09:21

本文选题：丁烯氟虫腈　切入点：微胶囊　出处：《山东农业大学》2017年博士论文　论文类型：学位论文

【摘要】：微胶囊制剂具有缓释控释提高药效持效期的作用,对农药的减量增效具有重要的意义。但是作为不太成熟的小剂型品种,其制备方法较为单一,且对其性能检测和释放机理的研究较少。本文选取丁烯氟虫腈原药为研究对象,使用层层自组装技术制备了多种类型微胶囊,同时对其制备工艺路线进行了描述评价,并对各种类型微胶囊的性能进行了对比分析。首先确定了层层自组装技术制备微胶囊的最佳条件,然后研究了不同组装层数、不同囊壁材料、不同缓释条件、不同囊芯物状态对微胶囊释放的影响。最后通过模拟释放动力学方程研究了层层自组装技术制备微胶囊的释放机理。本文主要研究结果可概括如下:1.微胶囊的制备(1)采用层层自组装技术以壳聚糖和海藻酸钠为壁材制备微胶囊,研究了制备过程中不同条件的变化对微胶囊包封率和缓释性能的影响,从而确定最佳制备条件:每层囊壁的组装时间为20 min;组装温度为室温;聚电解质溶液中盐离子浓度为0.5 mol/L;pH值在5.1左右。(2)分别使用CS/ALG、CS/SL、PAH/PSS为壁材制备不同组装层数的微胶囊,制备过程中测定了不同组装层数微胶囊的Zeta电势、平均粒径和表观形貌。研究结果表明三类壁材制备微胶囊过程中变化规律基本相同:Zeta电势随着组装正负聚电解质的加入发生周期性变化;微胶囊的平均粒径随着组装层数的增加逐渐增加;微胶囊颗粒表面的粗糙度也随着组装层数的增加而增加;通过红外光谱分析也可证明带有相反电荷的聚电解质已经成功地将丁烯氟虫腈固体原药包裹在囊芯内。(3)以壳聚糖和SDS为壁材制备了包覆液体溶液、油悬浮剂和固体颗粒的微胶囊,其中,溶液为丁烯氟虫腈二氯甲烷溶液,油悬浮剂使用的介质油为玉米油,分散剂为3478B。通过测定制备过程中的Zeta电势的变化、光学显微镜观察微胶囊的表观形貌来确定成功制备了包覆不同囊芯物状态的微胶囊。2.微胶囊的表征(1)以壳聚糖和海藻酸钠为壁材制备了不同组装层数的微胶囊,测定了不同组装层数微胶囊的表观形貌、包封率和载药量、抗光解性能。研究结果表明:随着组装层数的增加,微胶囊表面的粗糙度明显增加;载药量和包封率均是先升高再降低,当组装层数为4层时载药量达到最大值55%,而组装层数为6层时包封率达到最大值83%;随着组装层数的增加微胶囊中原药的光解率先快速降低,当组装层数为6层时光解率降到了21.7%,随后趋于平稳;(2)使用上述三类壁材制备了组装4层的微胶囊,比较了不同壁材微胶囊的包封率、载药量、抗光解性能的差异。研究结果表明:载药量和包封率的差异相同,pah/pss为壁材制备的微胶囊载药量和包封率均最好,cs/sl为壁材制备的微胶囊次之,cs/alg为壁材制备的微胶囊的载药量和包封率最小;三类壁材制备微胶囊抗光解能力由强到弱依次是cs/alg、pah/pss、cs/sl。3.微胶囊释放规律的研究(1)组装层数对微胶囊释放性能的影响不同组装层数微胶囊的释放规律基本相同,释放速率先快速升高,然后放缓。随着组装层数的增加微胶囊的缓释能力逐渐增强。且瞬时释放的峰值向后推迟。(2)囊壁材料对微胶囊释放性能的影响pah/pss为壁材制备的微胶囊缓释性能最好,而以cs/sl和cs/alg为壁材制备的微胶囊的缓释性能相差不大。(3)缓释条件对微胶囊释放性能的影响以壳聚糖和海藻酸钠为壁材制备组装6层的微胶囊为研究对象,研究了缓释介质中乙醇含量、盐离子浓度、ph、温度对微胶囊缓释性能的影响。研究结果表明:随着缓释介质中乙醇含量的增加,其释放速率逐渐增加;而随着缓释介质中外加盐离子浓度的增加,微胶囊的释放速率降低;缓释介质的ph为中性或者偏碱性微胶囊的释放速率基本相同,ph值为5时释放速率明显升高;升高缓释介质的温度能够显著提高微胶囊的缓释速率。(4)囊芯物状态对微胶囊释放性能的影响测定了不同囊芯物状态微胶囊的缓释情况,使用动力学方程模拟了不同微胶囊的释放曲线,研究结果表明:三类微胶囊的释放规律大体相同,一开始都具有“突释现象”,接着释放就会逐渐放缓,当囊芯物是溶液时,微胶囊的释放速率最快,而当囊芯物是油悬浮剂时,释放的速率最慢。4.释放动力学研究(1)不同组装层数微胶囊释放动力学研究将组装4层、6层和8层的微胶囊累积释放质量百分数低于60%的释放数据代入ritger-pappas模型,得到相应的的n值非常相近,说明它们的释放机理相同,为fick扩散和溶出机理的偶合,也就是说药物从微胶囊中释放是溶出和扩散共同控制的过程。(2)不同囊心物状态微胶囊释放动力学研究使用动力学方程模拟释放曲线可以知道在突释阶段,囊芯物为固体或者油悬浮剂时用Higuchi模型拟合的效果最好,释放符合Fick定律,当囊芯物为溶液时,药物以零级释放,对应于溶出控制机理。进入缓释阶段后,囊芯物是固体或者溶液的微胶囊在缓释阶段使用一级释放动力学方程拟合的效果较好,而当囊芯物是油悬浮时,其释放动力学曲线仍符合Higuchi模型。
[Abstract]:The micro capsule has the effect of sustained release efficacy duration, is of great significance to the reduction efficiency. But as pesticide immature small dosage varieties, the preparation method is single, and to test its performance and release mechanism research is less. This paper selects butylenes fipronil for technical research the object, using the self-assembly technology to prepare various types of micro capsule, and its preparation process are described, and performance of various types of micro capsules were studied. Firstly, optimum conditions of self-assembly technique for preparing microcapsules were determined, and then study the different assembly layers, different capsule wall materials, different release conditions, effects of different capsule core material of the microcapsule release state. Finally, through the simulation of release kinetics of release mechanism of self-assembly technique for preparing microcapsules. The main Research results can be summarized as follows: 1. preparation of microcapsule (1) by self-assembly technique using chitosan and sodium alginate as wall material of microencapsulation, study the influence of different conditions in the process of preparation of encapsulation efficiency and release property of microcapsules, so as to determine the optimal preparation conditions: assembly time of each layer of the cyst wall was 20 min; the assembly room temperature; poly salt ion concentration in the electrolyte is 0.5 mol/L; the pH value is about 5.1. (2) using CS/ALG, CS/SL, microcapsule wall material of PAH/PSS were prepared with different number of layers, in the preparation process of measuring the Zeta potential of different assembly the number of microcapsules, the average particle size and surface morphology. The results show that variation of the three types of wall material of microencapsulation process is basically the same: Zeta potential with the periodic change of positive and negative assembly of polyelectrolytes; the average particle size of microcapsules with assembly layers The increased; microcapsule particle surface roughness also increased with the increase of the number of the layers increases; the infrared spectral analysis also proved that the oppositely charged polyelectrolyte has successfully butenefipronil solid TC wrapped in the capsule core. (3) the wall materials were prepared by liquid solution with chitosan and SDS, microcapsule, oil suspension and solid particles in solution for butene fipronil dichloromethane solution, medium oil suspending agent used for corn oil, dispersing agent 3478B. through the changes of Zeta potential in the preparation process of measurement, optical microscopy micro capsule to determine the apparent morphology characterization.2. microcapsules with different capsule core material state of the microcapsules were prepared (1) microcapsules prepared by different layers of assembled wall material prepared using chitosan and sodium alginate, different assembly layers of microcapsules to measure the apparent morphology, The encapsulation efficiency and drug loading, anti photolysis performance. The results show that: with the increase of the number of the layers, microcapsule surface roughness increased significantly; the drug loading and encapsulation efficiency were increased first and then decreased, when the assembly layer is 4 when the loading rate reaches the maximum value of 55%, and the assembly of 6 layer at the encapsulation efficiency reached the maximum 83%; with the increase of the number of micro capsule assembly photolysis central medicine quickly took the lead to reduce, when the assembly layer is 6 time solution rate dropped to 21.7%, then remained stable; (2) using the above three kinds of wall material was prepared by assembling micro capsule 4 layer, different wall microcapsule encapsulation efficiency, drug loading, different anti photolysis performance. The results show that: the difference of loading and entrapment efficiency of the same pah/pss as the wall material of microcapsule by drug loading and encapsulation efficiency were the best, cs/sl the wall material of microcapsules prepared by microencapsulated cs/alg as the wall material preparation The entrapment efficiency and drug loading capacity of three kinds of minimum; anti photolysis wall material of microcapsule is prepared from strong to weak cs/alg, pah/pss, cs/sl.3. microcapsules release (1) release of assembly layers to influence the release property of microcapsules in different layers of assembled microcapsules are basically the same, the release rate of the first fast increased, then slow. With the ability to increase the number of the layers sustained-release microcapsules gradually. And the peak instantaneous release postponed. (2) the capsule wall material effect on release property of microcapsule wall material of pah/pss microcapsules prepared by the good sustained-release properties, cs/sl and cs/alg as the release property of the microcapsule wall material preparation are similar. (3) sustained release conditions on the release properties of microcapsules using chitosan and sodium alginate as wall material to prepare microcapsule assembling 6 layer as the research object, the research content of ethanol release medium, salt ion concentration, PH, the effect of temperature on the release characteristics of the microcapsule. The results show that with the increase of ethanol release medium, its release rate gradually increased; with the increase of salt concentration and release medium, the release rate of microcapsules decreased; release medium pH for release rate or alkaline microcapsule basic the same, pH value is 5 when the release rate increased significantly; increased release medium temperature can significantly increase the release rate of microcapsules. (4) capsule core material state determination of different slow-release capsule core material of microcapsules of state influence the release property of microcapsules, the simulation curves of different release microcapsules using kinetic equation the research results show that, three kinds of microcapsules release roughly the same, beginning with "burst release phenomenon", and then release will gradually slow down, when the capsule core material is the solution, the release speed of microcapsule The fastest rate, and when the capsule core material is oil suspension agent, release kinetics of the release rate of the slowest.4. (1) of different layers assembled microcapsules release kinetics of the assembly of the 4 layer, 6 layer and 8 layer of microcapsules and the cumulative release percentage is lower than the quality of release data into the ritger-pappas model 60%, corresponding the n values are very similar, that they have the same release mechanism, Fick diffusion and dissolution mechanism of coupling, that is to say the drug release from the microcapsule is dissolution and diffusion of the common control. (2) different capsule heart state micro capsule release kinetics using dynamic equation simulation release curve can know in the stage of burst release, capsule core material is solid or oil suspension fitted with Higuchi model had the best effect, release consistent with Fick's law, when the capsule core material for solution, drug release to zero level, corresponding to the dissolution into the release control mechanism. After the stage, the solid core of the capsule is solid or solution microcapsule. In the slow release stage, the first order release kinetics equation is better. When the core is oil suspension, the release kinetics curve is still consistent with the Higuchi model.

【学位授予单位】：山东农业大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：TQ450.6

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