目的:制备芦荟大黄素固体分散体(AE-SD),并测定AE和AE-SD在体内的代谢过程。
方法:以PEG-6000和PVP-K30为载体,通过溶剂蒸发或溶剂熔融制备AE-SD。热重分析,X射线衍射光谱,差示扫描量热法,利用傅里叶变换红外光谱和扫描电子显微镜对AE-SD的物理状态进行了鉴定。通过溶出度测定方法筛选出最佳处方。使用凤凰软件,对AE悬浮液和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体内行为的改变。在小鼠中评估急性毒性,并以生理毒性作为毒性的判定标准。
结果: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形式,并增加药物分散程度。因此,它更适合作为AE-SD的载体材料。泊洛沙姆(POL)的加入更有利于固体分散体的稳定性,并可以减少PVP的用量。溶出试验证实,AE与复合载体AE-PVP-POL的最佳配比为1:2:2,溶出效果最佳。根据药代动力学比较,与AE相比,AE-SD中药物吸收更快,并迅速达到血药浓度峰值,AE-SD的Cmax大于AE,AE-SD的t1/2和平均停留时间小于AE。结果表明,AE-SD中的药物代谢较好,停留时间较短。毒理学研究表明,AE和AE-SD均无毒性。
结论:本文确定,制备固体分散体后,药物的溶解度可以增加,如体外溶出实验所证明的。体内药代动力学研究证实,AE-SD可以提高AE在体内的生物利用度,为AE制剂的研发提供了新的概念。
OBJECTIVE: To prepare aloe-emodin solid dispersion (AE-SD) and determine the metabolic process of AE and AE-SD in vivo.
METHODS: AE-SD was prepared viasolvent 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 viathe dissolution degree determination method. Using Phoenix software, AE suspension and AE-SD were subjected to a pharmacokinetic comparison study analyzing the alteration of behavior in vivo 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.
RESULTS: 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.
CONCLUSIONS: This paper established that the solubility of the drug could be increased after preparing a solid dispersion, as demonstrated by in vitro dissolution experiments. In vivo pharmacokinetics studies confirmed that AE-SD could improve the bioavailability of AE in vivo, providing a new concept for the research and development of AE preparations.