药学学报, 2014, 49(3): 392-398
引用本文:
李雪, 郭桢, 郝结兵, 李彪, 刘从镖, 郭涛, 李海燕, 石森林, 汪六一, 张继稳. 脂质包裹与环糊精包合的协同矫味研究[J]. 药学学报, 2014, 49(3): 392-398.
LI Xue, GUO Zhen, HAO Jie-bing, LI Biao, LIU Cong-biao, GUO Tao, LI Hai-yan, SHI Sen-lin, WANG Liu-yi, ZHANG Ji-wen. Synergetic taste masking of lipid coating and β-cyclodextrin inclusion[J]. Acta Pharmaceutica Sinica, 2014, 49(3): 392-398.

脂质包裹与环糊精包合的协同矫味研究
李雪1,2, 郭桢2,4, 郝结兵3, 李彪3, 刘从镖2, 郭涛2, 李海燕2, 石森林1, 汪六一3, 张继稳1,2
1. 浙江中医药大学, 浙江 杭州 310000;
2. 中国科学院上海药物研究所, 上海 201203;
3. 海南卫康制药(潜山)有限公司, 安徽 安庆 246000;
4. 英国Bradford大学, Bradford, West Yorkshire BD7 1DP
摘要:
本文以对乙酰氨基酚为模型药物,研究脂质包裹与β-环糊精(β-CD)包合对难溶性苦味药物的协同矫味。通过建立动力学模型,计算药物在介质、脂质包裹微粒和分子包合等不同制剂单元中的分布,以控制产生苦味的游离药物浓度为目的,在制备、表征对乙酰氨基酚脂质微球基础上,确定β-CD用量,获得协同矫味给药体系,对其进行1H核磁共振(1H NMR)和分子模拟表征,并采用电子舌评价其矫味效果。结果脂质微球呈现一级释放,其速率常数为0.001 270 s-1,据此确定β-CD与对乙酰氨基酚的用量比为6.74:1(w/w)。协同矫味给药体系中对乙酰氨基酚1H NMR特征峰的化学位移值均增大,且酚羟基上的氧及亚胺基上的氮分别与β-CD中羟基上的氢形成分子间氢键。电子舌实验结合主成分分析(PCA)得到的苦味顺序为:协同矫味给药体系 ≈ 脂质微球<β-CD包合物<对乙酰氨基酚原料药,确证了脂质包裹与β-CD分子包合的协同矫味效果。综上,脂质包裹微球以物理包裹方式阻滞药物释放,β-CD通过分子间氢键对游离对乙酰氨基酚进行包合,有效降低产生苦味的游离药物浓度,实现了协同矫味。
关键词:    矫味      脂质微球      β-环糊精      电子舌      对乙酰氨基酚     
Synergetic taste masking of lipid coating and β-cyclodextrin inclusion
LI Xue1,2, GUO Zhen2,4, HAO Jie-bing3, LI Biao3, LIU Cong-biao2, GUO Tao2, LI Hai-yan2, SHI Sen-lin1, WANG Liu-yi3, ZHANG Ji-wen1,2
1. Zhejiang Chinese Medical University, Hangzhou 310000, China;
2. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China;
3. Hainan Weikang Pharmaceutical Co., LTD, Anqing 246000, China;
4. University of Bradford, Bradford, West Yorkshire BD7 1DP, United Kingdom
Abstract:
Paracetamol was used as a model drug in this study to investigate the synergetic effects of lipid coating and β-cyclodextrin (β-CD) inclusion for masking the bitter taste of poorly soluble drugs. To control the concentration as low as possible of the free drug which produced a bitter taste, a kinetic model was established to calculate the drug distribution theoretically among the free drug in medium, lipid coated particles and molecular inclusion on the basis of the preparation and characterization of the lipid microspheres, so as to select the proper amount of β-CD. Finally, the synergetic drug delivery systems were prepared and characterized by 1H nuclear magnetic resonance (1H NMR), molecular simulation and the electronic tongue. As a result, the drug release rate constant (k) of the lipid microspheres coated with octadecanol was determined as 0.001 270 s-1. Then, the synergetic drug delivery systems were prepared with the ratio of 6.74:1 (w/w) for β-CD and paracetamol. The chemical shift values for the fingerprint peaks of paracetamol all increased and hydrogen bonds were formed between the oxygen on the phenolic hydroxyl group, the nitrogen on the imino in paracetamol and the hydrogens on the hydroxyl groups in β-CD. The results tested by the electronic tongue indicated that the paracetamol, lipid microspheres, β-CD inclusion and their mixture showed different taste characteristics, with the bitterness order of the synergetic drug delivery systems ≈ lipid microspheres < β-CD inclusion < paracetamol, which confirmed the synergetic taste masking effects of lipid coating and β-CD molecular inclusion. In summary, the synergetic taste masking was jointly achieved through the retard of the drug release by the lipid coating and the inclusion of the free paracetamol by β-CD through hydrogen bonds.
Key words:    taste masking    lipid microsphere    β-cyclodextrin    electronic tongue    paracetamol   
收稿日期: 2013-10-09
基金项目: null
通讯作者: 张继稳 Tel/Fax:86-21-20231980,E-mail:jwzhang@simm.ac.cn;汪六一 Tel/Fax:86-556-8965095,E-mail:wangfeng1962@163.com;石森林 Tel/Fax:86-571-86613524,E-mail:pjstone@163.com
Email: jwzhang@simm.ac.cn;wangfeng1962@163.com;pjstone@163.com
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