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

doi:10.3969/j.issn.1004-1524.2021.03.04

Acta Agriculturae Zhejiangensis ›› 2021, Vol. 33 ›› Issue (3): 404-412.DOI: 10.3969/j.issn.1004-1524.2021.03.04

• Animal Science • Previous Articles Next Articles

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:2021-03-25 Published:2021-03-25
Contact: ZHANG Jiyu

Abstract

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

CLC Number:

S859.5

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.

Figures/Tables 12

References 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

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

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Figures/Tables 12

References 19

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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