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。 In this paper, paracetamol was used as a model drug to study the synergistic effect of lipid encapsulation and β-cyclodextrin (β-CD) inclusion on poorly soluble bitter drugs. By establishing a kinetic model to calculate the distribution of drugs in different preparation units such as medium, lipid-coated particles and molecular inclusion, and to control the concentration of free drug that produces bitterness, the preparation and characterization of paracetamol lipid microspheres On the basis of this, the amount of β-CD was determined and the synergistic drug delivery system was obtained. 1H nuclear magnetic resonance (NMR) and molecular simulation were used to characterize the flavonoids. The electronic tongue was used to evaluate the flavoring effect. Results The lipid microspheres showed a first order release with a rate constant of 0.001 270 s-1. Therefore, the ratio of β-CD to acetaminophen was 6.74:1 (w / w). Synergistic drug delivery system acetaminophen 1H NMR characteristic peak value of the chemical shift values ​​are increased, and the phenolic hydroxyl oxygen and imine nitrogen and β-CD, respectively, in the formation of hydrogen on the hydroxyl group intermolecular hydrogen key. The electronic tongue test combined with principal component analysis (PCA) showed that the order of bitterness was: synergistic delivery system ≈ lipid microspheres <β-CD inclusion