Key Laboratory of Basic and Application Research of Beiyao, Heilongjiang University of Chinese Medicine, Ministry of Education, Harbin 150040, China.
College of Pharmacy, Harbin Medical University, Harbin 150081, China.
J Tradit Chin Med. 2024 Feb;44(1):54-62. doi: 10.19852/j.cnki.jtcm.20231110.002.
To prepare aloe-emodin solid dispersion (AE-SD) and determine the metabolic process of AE and AE-SD .
AE-SD was prepared solvent evaporation or solvent melting using PEG-6000 and PVP-K30 as carriers. Thermogravimetric analysis, X-ray diffraction spectroscopy, differential scanning calorimetry, Fourier transform infrared spectroscopy and scanning electron microscopy were used to identify the physical state of AE-SD. Optimal prescriptions were screened the dissolution degree determination method. Using Phoenix software, AE suspension and AE-SD were subjected to a pharmacokinetic comparison study analyzing the alteration of behavior after AE was prepared as a solid dispersion. Acute toxicity was assessed in mice, and the physiological toxicity was used as the determination criterion for toxicity.
AE-SD showed that AE existed in the carrier in an amorphous state. Compared with polyethylene glycol, polyvinylpyrrolidone (PVP) inhibited AE crystallization, causing the drug to transform from a dense crystalline state to an amorphous form and increasing the degree of drug dispersion. Therefore, it was more suitable as a carrier material for AE-SD. The addition of poloxamer (POL) was more beneficial to the stability of solid dispersions and could reduce the amount of PVP. The dissolution test confirmed that the optimal ratio of AE to the composite vector AE-PVP-POL was 1：2：2, and its dissolution effect was also optimal. Based on the pharmacokinetic comparison, the drug absorption was faster and quickly reached the peak of blood drug concentration in AE-SD compared to AE, the Cmax of AE-SD was greater than that of AE, and t1/2 and mean residence time of AE-SD were less than AE. The results showed that the drug metabolism in AE-SD was better, and the residence time was shorter. The toxicology study showed that both AE and AE-SD had no toxicity.
This paper established that the solubility of the drug could be increased after preparing a solid dispersion, as demonstrated by dissolution experiments. pharmacokinetics studies confirmed that AE-SD could improve the bioavailability of AE , providing a new concept for the research and development of AE preparations.
制备大黄素固体分散体（AE-SD）并确定 AE 和 AE-SD 的代谢过程。
采用聚乙二醇 6000（PEG-6000）和聚乙烯吡咯烷酮 K30（PVP-K30）为载体，通过溶剂蒸发或溶剂熔融法制备 AE-SD。采用热重分析（TGA）、X 射线衍射光谱（XRD）、差示扫描量热法（DSC）、傅里叶变换红外光谱（FTIR）和扫描电子显微镜（SEM）对 AE-SD 的物理状态进行鉴定。筛选最佳处方，确定溶解度测定方法。采用 Phoenix 软件，对 AE 混悬液和 AE-SD 进行药代动力学比较研究，分析 AE 制备为固体分散体后行为的变化。采用小鼠急性毒性试验，以生理毒性为毒性判断标准。
AE-SD 表明 AE 以无定形状态存在于载体中。与聚乙二醇相比，聚乙烯吡咯烷酮（PVP）抑制 AE 结晶，使药物从致密结晶状态转变为无定形状态，增加药物分散程度，更适合作为 AE-SD 的载体材料。加入泊洛沙姆（POL）更有利于固体分散体的稳定性，可以减少 PVP 的用量。溶出试验证实，AE 与复合载体 AE-PVP-POL 的最佳比例为 1：2：2，其溶出效果也最佳。基于药代动力学比较，AE-SD 的药物吸收更快，血药浓度峰值迅速达到，与 AE 相比，AE-SD 的 Cmax 更大，t1/2 和平均驻留时间均小于 AE。结果表明，AE-SD 中的药物代谢更好，驻留时间更短。毒理学研究表明，AE 和 AE-SD 均无毒性。
本研究通过溶出实验证实，制备固体分散体后药物的溶解度可以提高。药代动力学研究证实，AE-SD 可以提高 AE 的生物利用度，为 AE 制剂的研究与开发提供了新的思路。
