响应面法优化沙拉沙星/β-环糊精包合物制备工艺与稳定性评价

doi:10.3969/j.issn.1004-1524.2021.03.04

浙江农业学报 ›› 2021, Vol. 33 ›› Issue (3): 404-412.DOI: 10.3969/j.issn.1004-1524.2021.03.04

响应面法优化沙拉沙星/β-环糊精包合物制备工艺与稳定性评价

姜兴粲¹^,²^,³, 李冰¹^,²^,³, 杨敏¹^,²^,³, 张继瑜¹^,²^,³^,^*()

1.农业农村部兽用药物创制重点实验室,甘肃兰州 730050
2.甘肃省新兽药工程重点实验室,甘肃兰州 730050
3.中国农业科学院兰州畜牧与兽药研究所,甘肃兰州 730050

收稿日期:2020-01-25 出版日期:2021-04-02 发布日期:2021-03-25
通讯作者: 张继瑜
作者简介:*, 张继瑜,E-mail: infzjy@sina.com
姜兴粲(1994—),男,山东菏泽人,硕士研究生,主要从事兽医药理学与毒理学研究。E-mail: Jiangxingcan0908@163.com
基金资助:
“十二五”国家科技支撑计划(2015BAD1101);国家现代农业产业技术体系专项(CAR-37)

Optimization of preparation technology and stability evaluation of sarafloxacin/β-cyclodextrin inclusion complex by response surface method

JIANG Xingcan¹^,²^,³, LI Bing¹^,²^,³, YANG Min¹^,²^,³, ZHANG Jiyu¹^,²^,³^,^*()

1. Key Laboratory of Veterinary Pharmaceutical Development, Ministry of Agriculture and Rural Affairs, Lanzhou 730050, China
2. Key Laboratory of New Animal Drug Project of Gansu Province, Lanzhou 730050, China
3. Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China

Received:2020-01-25 Online:2021-04-02 Published:2021-03-25
Contact: ZHANG Jiyu

摘要/Abstract

摘要：

为制备沙拉沙星/β-环糊精包合物微囊,解决沙拉沙星原药溶解度低,理化性质不稳定的问题。通过响应面法优化沙拉沙星/β-环糊精包合物的制备工艺,采用液相色谱法对沙拉沙星/β-环糊精包合物进行载药量及溶解度测定,以干燥失重试验和影响因素试验对沙拉沙星/β-环糊精包合物的含水量与稳定性进行评价。结果显示,优化后的包合工艺参数为沙拉沙星与β-环糊精摩尔比1∶2,搅拌温度50 ℃,搅拌时间4 h,喷雾干燥工艺为温度160 ℃,泵速6.3 r·min ^-1。液相色谱方法学结果表明:沙拉沙星在质量浓度9.94~99.40 μg·mL ^-1范围内,线性关系优良,回归方程为Y=34.66X-15.867,相关系数为0.999 9。影响因素试验与干燥失重试验表明,制备的沙拉沙星/β-环糊精包合物物理化学性质稳定,包合物含水量小于2%,流动性良好。结果表明,沙拉沙星/β-环糊精包合物的成功制备明显改善了药物的理化性质,对沙拉沙星的应用与推广具有积极作用。

关键词: 沙拉沙星, β-环糊精;, 包合物, 制备工艺, 响应面法

Abstract: To prepare sarafloxacin/β-cyclodextrin inclusion complex microcapsules, and to solve the problems of low solubility and unstable physicochemical properties of sarafloxacin, the preparation process of sarafloxacin/β-cyclodextrin inclusion complex was optimized by response surface method, and the drug loading and solubility of sarafloxacin/β-cyclodextrin inclusion complex were determined by high performance liquid chromatography(HPLC). The water content and stability of sarafloxacin/β-cyclodextrin inclusion complex were evaluated by drying weight loss test and influencing factors experiment. The results showed that the optimized inclusion process parameters were as follows: molar ratio of sarafloxacin to β-cyclodextrin 1:2, stirring temperature 50 ℃, stirring time 4 h, spray drying temperature 160 ℃, pump speed 6.3 r?min-1. The results of the liquid chromatographic methodology verified showed that the linear relationship of sarafloxacin was good in the range of 9.94~99.40 μg?mL-1. The regression equation was Y=34.66X-15.867, and the correlation coefficient was 0.999 9. The experiments of influencing factors and drying weight loss showed that the physical and chemical properties of the prepared sarafloxacin/β-cyclodextrin inclusion complex were stable, the water content of the inclusion complex was less than 2%, and the fluidity was good. The results showed that the successful preparation of sarafloxacin/β-cyclodextrin inclusion complex significantly improved the physical and chemical properties of the drug and played a positive role in the application and popularization of sarafloxacin.

Key words: sarafloxacin, β-cyclodextrin;, inclusion complex, preparation technology, response surface method

中图分类号:

S859.5

姜兴粲, 李冰, 杨敏, 张继瑜. 响应面法优化沙拉沙星/β-环糊精包合物制备工艺与稳定性评价[J]. 浙江农业学报, 2021, 33(3): 404-412.

JIANG Xingcan, LI Bing, YANG Min, ZHANG Jiyu. Optimization of preparation technology and stability evaluation of sarafloxacin/β-cyclodextrin inclusion complex by response surface method[J]. Acta Agriculturae Zhejiangensis, 2021, 33(3): 404-412.

图/表 12

参考文献 19

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水平 Level	SAR与β-CD摩尔比 Molar ratio of SAR and β-CD	θ/℃	t/h
1	1∶1	40	3
2	1∶2	50	4

水平 Level	SAR与β-CD摩尔比 Molar ratio of SAR and β-CD	θ/℃	t/h
1	1∶1	40	3
2	1∶2	50	4

水平 Level	进气温度 Intake air temperature/℃	泵速 Pump speed/(r·min^-1)
1	135	6.0
2	150	6.3
3	165	6.6

水平 Level	进气温度 Intake air temperature/℃	泵速 Pump speed/(r·min^-1)
1	135	6.0
2	150	6.3
3	165	6.6

方差来源 Variance source	均方 Mean square	自由度 df	均方差 Mean square error	F值 F value	P值 P value
模型 Model	4083.69	9	453.74	19.46	0.0004
A	1128.13	1	1128.13	48.37	0.0002
B	338.00	1	338.00	14.49	0.0067
C	528.13	1	528.13	22.65	0.0021
AB	36.00	1	36.00	1.54	0.2541
AC	156.25	1	156.25	6.70	0.0360
BC	16.00	1	16.00	0.69	0.4348
A²	671.12	1	671.12	28.78	0.0010
B²	295.33	1	295.33	12.66	0.0092
C²	725.33	1	725.33	31.10	0.0008
残差 Residual	163.25	7	23.32
失拟项 Lack of fit	163.25	3	54.42
纯误差 Pure error	0.000	4	0.000

响应面法优化沙拉沙星/β-环糊精包合物制备工艺与稳定性评价

Optimization of preparation technology and stability evaluation of sarafloxacin/β-cyclodextrin inclusion complex by response surface method

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图/表 12

参考文献 19

相关文章 9

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Metrics

本文评价

方差来源 Variance source	均方 Mean square	自由度 df	均方差 Mean square error	F值 F value	P值 P value
模型 Model	21397.99	5	4279.60	17.84	0.0007
D	7285.53	1	7285.53	30.38	0.0009
E	7285.53	1	7285.53	30.38	0.0009
DE	2500.00	1	2500.00	10.42	0.0145
D²	2445.65	1	2445.65	10.20	0.0152
E²	2445.65	1	2445.65	10.20	0.0152
残差 Residual	1678.93	7	239.85
失拟项 Lack of fit	1678.93	3	559.64
纯误差 Pure error	0.000	4	0.000

初始质量 Initial weight/g	3 h后质量 Weight after 3 h/g	3 h后质量损失 Weight loss after 3 h/g	4 h后质量损失 Weight loss after 4 h/g	4.5 h后质量损失 Weight loss after 4.5 h/g
1.1165	1.1151	0.0014	0.0006	0.0002
0.9058	0.9043	0.0015	0.0005	0.0002
0.9675	0.9660	0.0015	0.0005	0
1.2946	1.2932	0.0014	0.0006	0
1.1341	1.1327	0.0014	0.0007	0.0002
1.0125	1.0111	0.0014	0.0005	0.0001

保存时间 Storage time/d	批次 Number	相对含量 Relative content/%	单一杂质 Single impurity/%	总杂质 Total impurities/%	有关物质 Relative substance/%
5	1	100.35	<0.5	<1.0	<0.5
	2	99.21	<0.5	<1.0	<0.5
	3	100.16	<0.5	<1.0	<0.5
10	1	96.11	<0.5	<1.0	<0.5
	2	99.76	<0.5	<1.0	<0.5
	3	100.91	<0.5	<1.0	<0.5

保存时间 Storage time/d	批次 Number	相对含量 Relative content/%	单一杂质 Single impurity/%	总杂质 Total impurities/%	有关物质 Relative substance/%
5	1	96.43	<0.5	<1.0	<0.5
	2	98.05	<0.5	<1.0	<0.5
	3	97.21	<0.5	<1.0	<0.5
10	1	95.61	<0.5	<1.0	<0.5
	2	95.33	<0.5	<1.0	<0.5
	3	96.02	<0.5	<1.0	<0.5

保存时间 Storage time/d	批次 Number	吸湿后质量增加比例 Hygroscopic weight gain	相对含量 Relative content/%	单一杂质 Single impurity/%	总杂质 Total impurities/%	有关物质 Relative substance/%
5	1	<5%	96.54	<0.5	<1.0	<0.5
	2	<5%	100.03	<0.5	<1.0	<0.5
	3	<5%	98.65	<0.5	<1.0	<0.5
10	1	<5%	95.39	<0.5	<1.0	<0.5
	2	<5%	100.10	<0.5	<1.0	<0.5
	3	<5%	98.05	<0.5	<1.0	<0.5

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批次 Number	载药量 Drug loading/%	溶解度 Solubility/(mg·mL^-1)
1	90.17	15.08
2	90.48	15.08
3	90.34	13.92

批次 Number	载药量 Drug loading/%	溶解度 Solubility/(mg·mL^-1)
1	90.17	15.08
2	90.48	15.08
3	90.34	13.92