杨佳佳 李婉蓉 彭剑青 肖婷 吴林菁 周雪 杨增秋 姜丰 丁杨 沈祥春 陶玲

中圖分类号 R944.1 文献标志码 A 文章编号 1001-0408（2020）14-1704-07

DOI 10.6039/j.issn.1001-0408.2020.14.08

摘 要 目的：优化香茅醇亚微乳的制备工艺。方法：采用高效液相色谱法测定香茅醇亚微乳中的香茅醇含量;采用高速剪切分散-高压均质法制备香茅醇亚微乳，以离心稳定常数（ke）、粒径为指标，对其处方及工艺进行优化并进行验证;测定所得制剂的载药量的包封率。结果：香茅醇检测质量浓度的线性范围为4～64 μg/mL（R 2= 0.999 9）;精密度、稳定性（24 h）、重复性试验的RSD均小于3%;加样回收率为97.64%～101.97%（RSD=2.28%，n=3）、97.71%～99.50%（RSD=1.29%，n=3）、96.87%～101.48%（RSD=2.86%，n=3）。最优处方为大豆油+中链甘油三酯（1 ∶ 1，g/g）总质量3.75 g，1.2%大豆磷脂0.6 g，胆固醇0.06 g，香茅醇1.25 g，0.6%油酸钠0.3 g，15-羟基硬脂酸聚乙二醇酯0.75 g，泊洛沙姆188 0.75 g，加水至50 mL。最优工艺为于4 ℃下以13 000 r/min高速剪切5 min制得初乳后，经稀盐酸调pH至7，再以600 Bar高压均质5 min。按最优处方及工艺制备的3批香茅醇亚微乳的平均粒径为（91.05±0.26）nm，多分散系数为（0.20±0.01），Zeta电位为（-30.86±0.39）mV，ke值为9.23，香茅醇的平均含量为（100.21±0.01）%;载药量为（2.481 7±0.000 7）mg/mL，包封率为（99.27±0.03）%。结论：优化所得处方及工艺稳定、可行。

关键词 香茅醇;亚微乳;高速剪切分散-高压均质法;处方;工艺;优化;高效液相色谱法;含量

Study on Optimization of Formulation and Technology of Citronellol Submicroemulsion

YANG Jiajia1，LI Wanrong1，PENG Jianqing1，XIAO Ting1，WU Linjing1，ZHOU Xue1，YANG Zengqiu1，JIANG Feng1，DING Yang2，SHEN Xiangchun1，TAO Ling1（1. School of Pharmacy， Guizhou Medical University/Engineering Center for the Highly Efficient Utilization of Natural Medicine Resources in Guizhou Province/Key Lab for Pharmacology and Pharmacogenesis Evaluation of Natural Medicine in Guizhou Universities/Guizhou Medical University-Guiyang Joint Key Laboratory/Key Laboratory for Optimal Utilization of Natural Medicine Resources， Guiyang 550025， China; 2. Pharmaceutics Teaching and Research Section， China Pharmaceutical University/State Key Laboratory of Bioactive Substance and Function of Natural Medicines， Nanjing 210009， China）

ABSTRACT   OBJECTIVE： To optimize the preparation technology of citronellol submicroemulsion. METHODS： The content of citronellol in Citronellol submicroemulsion was determined by HPLC. Citronellol submicroemulsion by high-speed shearing dispersion-high pressure homogenization method， with centrifugation stability constant （ke） and particle size were used as evaluation indexes. Its formulation and preparation technology were optimized and validated. Drug-loading amount and encapsulation rate of the preparation were detected. RESULTS： The linear range of citronellol were 4-64 μg/mL （R 2=0.999 9）. RSDs of precision， stability （24 h） and reproducibility tests were all lower than 3%. The recoveries were 97.64%-101.97%（RSD=2.28%，n=3）， 97.71%-99.50%（RSD=1.29%，n=3）， 96.87%-101.48%（RSD=2.86%，n=3）. The optimal formulation included that total weight of soybean oil and medium chain triglycerides （1 ∶ 1，g/g） was 3.75 g， 1.2% soybean phospholipid was 0.6 g， cholesterol was 0.06 g， citronellol was 1.25 g， 0.6 % sodium oleate was 0.3 g， 15-hydroxystearic acid polyethylene glycol ester was 0.75 g， poloxamer 188 was 0.75 g， water added to 50 mL. After prepared by optimal technology at 4 ℃ which contained shearing speed of 13 000 r/min， lasting for 5 min， primary emulsion was adjusted to pH 7 with dilute hydro- chloric acid， and homogenized with 600 Bar high pressure for 5 min. The parameters of Citronellol submicroemulsion accor- ding to optimal formulation and technology contained mean particle size of （91.05±0.26） nm， PDI of （0.20±0.01）， Zeta-potential of （-30.86±0.39） mV， average content of citronellol （100.21±0.01） %， the drug-loading amount was （2.481 7±0.000 7） mg/mL， the encapsulation rate was （99.27±0.03）%. CONCLUSIONS： The optimal formulation and technology is stable and feasible.

KEYWORDS   Citronellol; Submicroemulsion; High-speed shearing dispersion-high pressure homogenization method; Formula- tion;Technology; Optimization; HPLC; Content

香茅醇是一种于香茅属植物香茅[Cymbopogon citratus （dC.） Stapf]精油中发现的单萜烯类化合物[1]。目前，香茅醇已被作为添加剂广泛应用于烟草、日化及食品领域[2-3]。有研究发现，该化合物具有抗菌、抗炎、镇痛、抗氧化和抗肿瘤等药理作用[4-5]。本课题组前期研究发现，香茅醇对人喉癌上皮细胞Hep-2具有显著的增殖抑制作用。但因香茅醇挥发性较强，对光线、氧气、温度等条件较敏感，且难溶于水，故其临床应用受到限制[6]。……