药用肠溶包衣材料的合成研究
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摘要
使用含羧基功能单体甲基丙烯酸(MAA),采用间歇聚合和种子半连续乳液聚合方法制备了具有肠溶性的共聚物乳液。简化了包衣生产过程,克服了使用有机溶剂带来的污染,而且共聚物具有自增塑效果,避免了增塑剂的使用。
水溶性单体MAA的共聚使得乳液聚合体系较为复杂,本文系统研究了乳化剂种类和用量、引发剂用量、聚合温度、功能单体含量和单体加料方式及加料速率对聚合体系稳定性、转化率和共聚物膜性能的影响。结果表明:阴离子型乳化剂SDS与非离子型乳化剂OP-10(3 : 2)复配且用量为3%时乳化效果最佳;少量MAA(2wt%)的引入可以提高聚合速率,但是当MAA含量较高(>30wt%)时,它的存在使得体系稳定性、转化率都有所下降;减慢单体的加料速率可以抑制MAA的均聚倾向,提高聚合稳定性和单体转化率。研究了在种子乳液聚合过程中乳胶粒径随时间的变化,结果表明加料速率加快、单体中MAA含量增大都使乳胶粒聚并现象明显,粒径增大。研究了乳液成膜后肠溶性的影响因素,结果表明:MAA含量增大、共聚程度增加、链转移剂的使用均有利于提高肠溶性。
采用TEM、IR、1H-NMR、DSC对共聚物进行了表征:TEM结果表明聚合物乳液的粒径在80nm左右,具有典型的核壳结构;DSC数据显示聚合物具有单一的Tg,不存在相分离;使用IR、1H-NMR分析了共聚物的组成,采用种子半连续乳液聚合,减慢单体滴加速度可以使共聚物组成与单体组成基本相同。
利用电导滴定和酸值滴定数据分析了MAA在乳胶粒内部、乳胶粒表面以及水溶液中的分布。结果表明:MAA用量增加、单体加料速度增大,水相MAA浓度随之增加,因而MAA水相均聚程度增加,导致乳胶粒内部MAA含量减少。
The copolymer latex of Methacrylic acid(MAA), which can be used as enteric-soluble coating materials, was prepared in both batch and semi-batch seeded emulsion copolymerizations. The effects of emulsifier type and amount, initiator amount, copolymerization temperature, content of MAA, monomers feeding rate on the latex stability and monomers conversion were investigated. It was shown that a percentage of 2 wt.% MAA in monomers led to the acceleration of polymerization rate, while emulsion stability was not affected obviously. When the percentage of MAA was increased, more than 30 wt.%,the coagulation between latex particles and coagulum became serious with increasing MAA contents especially in the batch polymerization processes. However, the solubility of copolymers in alkali medium increased with increasing MAA contents in copolymer.
It was shown that a reduction of the monomers feeding rate is favorable to the process. The growth of particles was studied primarily in the semi-batch seeded emulsion copolymerization, it was shown that the decrease of the monomers feeding rate and MAA content can promote copolymerization, obtaining smaller particles. Factors that influenced the enteric-solubility of the film were also studied. An increase of MAA content and decrease of the molecular weight of copolymer will favor the solution process.
TEM result showed that the latex diameter was about 80nm, with a core-shell structure. The copolymer was also determined by 1H-NMR, IR, DSC spectra. The distribution of MAA in latex inside, latex surface, aqueous phase were characterized by conductometric and acidimetric titration.It was shown that the MAA concentration in aqueous phase increased with the increase of monomers feeding rate and MAA content,thus MAA in copolymer reduced due to the increasing tendency of MAA homopolymerization in water.
水溶性单体MAA的共聚使得乳液聚合体系较为复杂,本文系统研究了乳化剂种类和用量、引发剂用量、聚合温度、功能单体含量和单体加料方式及加料速率对聚合体系稳定性、转化率和共聚物膜性能的影响。结果表明:阴离子型乳化剂SDS与非离子型乳化剂OP-10(3 : 2)复配且用量为3%时乳化效果最佳;少量MAA(2wt%)的引入可以提高聚合速率,但是当MAA含量较高(>30wt%)时,它的存在使得体系稳定性、转化率都有所下降;减慢单体的加料速率可以抑制MAA的均聚倾向,提高聚合稳定性和单体转化率。研究了在种子乳液聚合过程中乳胶粒径随时间的变化,结果表明加料速率加快、单体中MAA含量增大都使乳胶粒聚并现象明显,粒径增大。研究了乳液成膜后肠溶性的影响因素,结果表明:MAA含量增大、共聚程度增加、链转移剂的使用均有利于提高肠溶性。
采用TEM、IR、1H-NMR、DSC对共聚物进行了表征:TEM结果表明聚合物乳液的粒径在80nm左右,具有典型的核壳结构;DSC数据显示聚合物具有单一的Tg,不存在相分离;使用IR、1H-NMR分析了共聚物的组成,采用种子半连续乳液聚合,减慢单体滴加速度可以使共聚物组成与单体组成基本相同。
利用电导滴定和酸值滴定数据分析了MAA在乳胶粒内部、乳胶粒表面以及水溶液中的分布。结果表明:MAA用量增加、单体加料速度增大,水相MAA浓度随之增加,因而MAA水相均聚程度增加,导致乳胶粒内部MAA含量减少。
The copolymer latex of Methacrylic acid(MAA), which can be used as enteric-soluble coating materials, was prepared in both batch and semi-batch seeded emulsion copolymerizations. The effects of emulsifier type and amount, initiator amount, copolymerization temperature, content of MAA, monomers feeding rate on the latex stability and monomers conversion were investigated. It was shown that a percentage of 2 wt.% MAA in monomers led to the acceleration of polymerization rate, while emulsion stability was not affected obviously. When the percentage of MAA was increased, more than 30 wt.%,the coagulation between latex particles and coagulum became serious with increasing MAA contents especially in the batch polymerization processes. However, the solubility of copolymers in alkali medium increased with increasing MAA contents in copolymer.
It was shown that a reduction of the monomers feeding rate is favorable to the process. The growth of particles was studied primarily in the semi-batch seeded emulsion copolymerization, it was shown that the decrease of the monomers feeding rate and MAA content can promote copolymerization, obtaining smaller particles. Factors that influenced the enteric-solubility of the film were also studied. An increase of MAA content and decrease of the molecular weight of copolymer will favor the solution process.
TEM result showed that the latex diameter was about 80nm, with a core-shell structure. The copolymer was also determined by 1H-NMR, IR, DSC spectra. The distribution of MAA in latex inside, latex surface, aqueous phase were characterized by conductometric and acidimetric titration.It was shown that the MAA concentration in aqueous phase increased with the increase of monomers feeding rate and MAA content,thus MAA in copolymer reduced due to the increasing tendency of MAA homopolymerization in water.
引文
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