季铵化聚丙烯酸树脂Ⅳ交联型骨架片的制备及防滥用性能考察  

Preparation of Matrix Tablets with Cross-linked Quaternized Polyacrylic ResinⅣand Its Anti-abuse Performance

作　　者：王莉 哈及尼沙[1] 李凤和 李效文 姚日生[3] WANG Li;Hajinisa;LI Fenghe;LI Xiaowen;YAO Risheng(College of Pharmacy,Xinjiang Medical University,Urumqi 830011;Anhui Ansheng Biochemical Technology Co.,Ltd.,Hefei 230002;Dept.of Pharmaceutical Science and Engineering,Hefei University of Technology,Hefei 230009)

机构地区：[1]新疆医科大学药学院,新疆乌鲁木齐830011 [2]安徽安生生物化工科技有限责任公司,安徽合肥230002 [3]合肥工业大学药物科学与工程系,安徽合肥230009

出　　处：《中国医药工业杂志》2021年第9期1208-1214,1223,共8页Chinese Journal of Pharmaceuticals

基　　金：新疆天然药物活性组分与释药技术重点实验室(XJDX1713);国家“重大新药创制”科技重大专项——聚丙烯酸酯共聚物水分散体关键技术开发及应用(2018ZX09721002)。

摘　　要：阿片类药物误用和滥用日益增加,需要新型高性能防药物滥用的辅料。为此,本研究以聚丙烯酸树脂Ⅳ的结构特点为出发点,先进行季铵化处理,再采用制剂后固态交联法以阿司匹林为模型药制备防滥用制剂。考察了所得完整和非完整的片剂在无水乙醇中60 min的溶出量,以表征溶剂提取效果。结果表明,60 min内无水乙醇对完整片剂中药物的最大提取率仅为(5.82±0.59)%;对非完整片剂中药物的提取率较高,且固化温度对提取率有显著影响:50℃固化的片剂的提取率在60 min时高达(65.8±0.5)%,而60和70℃固化的片剂中药物提取率低于10%。体外释放试验表明,该片剂在pH 1.2盐酸中的释放速度和程度随着固化温度的升高而降低,在pH 6.8磷酸盐缓冲液中6 h累积释放率大于60%。本试验表明,季铵化聚丙烯酸树脂Ⅳ不仅可作为防滥用药物制剂的特种辅料,同时也可作为药物缓控释制剂的常规辅料。With the increasing of misuse and abuse of opioids,new high-performance excipients are needed to prevent drug abuse.According to the structural characteristics of polyacrylic acid resinⅣ,we firstly synthesized the quaternized polyacrylic acid resinⅣ.Then,the anti-abuse tablets were prepared with aspirin as a model drug and the above resin by curing at different temperatures(namely cross-linking in solid state).The dissolution amount of the intact and incomplete tablets at 60 min in absolute ethanol were used as the indicator of the solvent extraction effect.The results showed that the maximun extraction rate of the drug from the intact tablet was(5.82±0.59)%.To incomplete tablets,the curing temperature had a significant effect on the extraction rate.The extraction rate of the drug from the incomplete tablets cured at 50℃reached(65.8±0.5)%within 60 min,while the extraction rates of the incomplete tablets cured at 60 and 70℃were less than 10%.The in vitro release test showed that the release rate and extent of the tablets in pH 1.2 hydrochloric acid decreased with the increasing of the curing temperature,but the cumulative release rates in pH 6.8 phosphate buffer for 6 h of the tablets cured at different temperatures were all above 60%.In conclusion,the quaternized polyacrylic acid resinⅣcan not only be used as a special excipient for anti-abuse formulation,but also as a conventional excipient for sustained-and controlled-release preparations.

关 键 词：季铵化改性 聚丙烯酸树脂Ⅳ 骨架片 防滥用 交联 释放 

分 类 号：R944.4[医药卫生—药剂学]