Page 80 - 《中国药房》2022年4期

神经酸口服乳剂的处方及制备工艺优化 Δ

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陈文静 ，付加雷 ，孙丹丹 ，于蓓蓓 ，生立嵩 ，闫雪生 （1.山东中医药大学药学院，济南 250355；2.山东省中
医药研究院，济南 250014）
中图分类号 R943 文献标志码 A 文章编号 1001-0408（2022）04-0458-07
DOI 10.6039/j.issn.1001-0408.2022.04.13
摘 要 目的 制备神经酸口服乳剂，对其处方及制备工艺进行优化，并考察其稳定性。方法 通过机械法制备神经酸口服乳剂。
在单因素实验的基础上，以乳剂外观、离心稳定性、离心稳定常数（Ke ）、粒径为指标，采用正交实验设计，以油酸用量、辛基苯酚聚
氧乙烯醚-10用量、丙二醇用量为因素，对其处方进行优化；以乳化温度、剪切时间、高压均质压力、高压均质循环次数为因素，对其
制备工艺进行优化；采用高效液相色谱法测定神经酸含量，采用高温试验、加速试验和长期试验考察神经酸口服乳剂的稳定性。
结果 最优处方及制备工艺为神经酸原料药1 g、油酸用量5％、辛基苯酚聚氧乙烯醚-10用量4％、丙二醇用量2％、乳化温度60 ℃、
剪切时间 2 min、高压均质压力 40 MPa、高压均质循环 2 次。经 3 次实验验证，所得神经酸口服乳剂的平均粒径为 158.05 nm
（RSD＝1.58％，n＝3），平均Ke为0.39（RSD＝1.49％，n＝3），外观呈均一乳白色，均无分层现象。高温试验结果显示，神经酸口服
乳剂在高温环境中易出现分层现象，神经酸的含量有所增加；加速试验及长期试验结果显示，神经酸口服乳剂在室温下放置6个
月的外观、神经酸含量均无明显变化。结论 所得最优处方及制备工艺稳定、可行，可用于神经酸口服乳剂的制备；神经酸口服乳
剂不适宜放置于高温环境中，在室温环境下放置6个月的稳定性较好。
关键词 神经酸口服乳剂；处方优化；制备工艺优化；正交实验设计；高效液相色谱法；样品稳定性

Optimization of formulation and preparation technology of Neuritic acid oral emulsion
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CHEN Wenjing ，FU Jialei ，SUN Dandan ，YU Beibei ，SHENG Lisong ，YAN Xuesheng（1. School of Pharmacy，
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Shandong University of Traditional Chinese Medicine，Jinan 250355，China；2. Shandong Academy of Chinese
Medicine，Jinan 250014，China）
ABSTRACT OBJECTIVE To prepare Neuritic acid oral emulsion，to optimize its formulation and preparation technology，and
to investigate its stability. METHODS Neuritic acid oral emulsion was prepared by mechanical method. On the basis of single
factor experiment，the appearance，centrifugal stability，centrifugal stability constant （Ke ） and particle size of the emulsion as
indexes，the formulation was optimized by orthogonal design，taking the dosage of oleic acid，octylphenol polyoxyethylene
ether-10 and propylene glycol as factors，the preparation technology was optimized by taking emulsification temperature，shear
time，pressure of high-pressure homogenization and cycle times of high-pressure homogenization as factors. The content of neuritic
acid was determined by high performance liquid chromatography. The stability of Neuritic acid oral emulsion was investigated by
high temperature test，accelerated test and long-term test. RESULTS The optimal formulation and preparation technology were as
follows：neuritic acid of 1 g，oleic acid of 5％ ，octylphenol polyoxyethylene ether-10 of 4％ ，propylene glycol of 2％ ，
emulsification temperature of 60 ℃ ，shear time of 2 min，homogenization pressure of 40 MPa and cycle times of twice. After

three experiments，the average particle size of Neuritic acid oral emulsion was 158.05 nm（RSD＝1.58％，n＝3），the average Ke
was 0.39（RSD＝1.49％，n＝3），and the appearance was uniform milky white，there was no stratification. The results of high
temperature test showed that Neuritic acid oral emulsion was prone to stratification in high temperature environment，and the
content of neuritic acid increased. The results of accelerated test and long-term test showed that there was no significant change in
the appearance or the content of neuritic acid when Neuritic acid oral emulsion was placed at room temperature for 6 months.
CONCLUSIONS The formulation and preparation technology are stable and feasible，and can be used for the preparation of
Neuritic acid oral emulsion. Neuritic acid oral emulsion should not be placed in high temperature environment. It has good stability
at room temperature for 6 months.
KEYWORDS Neuritic acid oral emulsion；formulation optimization；preparation technology optimization；orthogonal design；
high performance liquid chromatography；sample stability
神经酸是一种含 24 个碳原子和 1 个双键的不饱和
Δ 基金项目：山东省中医药科技发展计划项目（No.2019-0209）
脂肪酸，最早被发现于哺乳动物的神经组织中 。神经
[1]
＊硕士研究生。研究方向：中药制剂新剂型、新制剂及物质基
酸是构成大脑神经细胞和神经组织的核心天然成分，能
础。E-mail：chwjzyy@163.com
# 通信作者：研究员，硕士生导师，硕士。研究方向：中药制剂新 促进受损神经组织修复和再生，对防止脑神经细胞衰老
[2]
剂型、新制剂及物质基础。E-mail：tcmyxs@126.com 有很大作用 。神经酸具有多种药理活性，如健脑益智、
·458 · China Pharmacy 2022 Vol. 33 No. 4 中国药房 2022年第33卷第4期