白屈菜红碱固体分散体的制备及其理化性质和抗氧化活性研究(1)
中圖分类号 R944.2+4 文献标志码 A 文章编号 1001-0408(2020)09-1054-08
DOI 10.6039/j.issn.1001-0408.2020.09.07
摘 要 目的：制备白屈菜红碱(CHE)固体分散体(SD)，优化其处方工艺，并对所制产品进行表征和体外抗氧化活性考察。方法：采用紫外分光光度法测定SD中CHE的含量;在单因素试验的基础上，以产品收率为指标，以制备方法、载体材料种类、载体比例(药物-载体材料质量比)为考察因素，采用L9(34)正交试验优化SD的处方工艺并进行验证。在检测溶解度和累积溶出度的基础上，采用热分析法、X-射线衍射法和扫描电子显微镜等技术对产品进行物相表征;以抗坏血酸为阳性对照，采用1，1-二苯基-2-三硝基苯肼法(DPPH)测定产品的体外抗氧化活性。结果：CHE检测质量浓度的线性范围为2.4～5.6 μg/mL，定量限、检测限分别为0.066 9、0.022 1 μg/mL;精密度、稳定性、重复性试验的RSD均小于2%，加样回收率为97.50%～99.25%(RSD<1%，n=3)。最优制备工艺是以聚乙二醇6000(PEG 6000)为载体、载体比例为1 ∶ 3，采用溶剂法制备。按最优工艺制得3批CHE-PEG-SD，验证试验结果显示，其在15 min时的累积溶出度为(61.72±0.67)%，收率为(99.04±0.83)%。表征结果显示，制成CHE-PEG-SD后，其溶解度(3.725 mg/mL)和累积溶出度(61.72%，15 min)均高于CHE原料药[0.098 mg/mL，6.24%(180 min)];其吸热峰、晶体吸收峰均较原料药和载体有所移动甚至消失，CHE以非晶态均匀分散于载体中。体外抗氧化试验结果显示，不同质量浓度的CHE-PEG-SD均具有一定的DPPH自由基清除能力，半数抑制浓度为0.124 mg/mL，但高于抗坏血酸的0.041 mg/mL。结论：所建含量测定方法简便、准确;优化的SD处方工艺稳定、可行;所制CHE-PEG-SD的溶解度增大，体外溶出增多，且具有一定的体外抗氧化活性。
关键词 白屈菜红碱;固体分散体;工艺优化;体外溶出;表征;抗氧化活性
Preparation of Chelerythrine Solid Dispersion and Study on Its Physicochemical Properties and Antioxidant Activity
WANG Yun1，2，3，LI Pingping1，3，4，GAO Zhenshen1，ZHANG Xiaoping1，3，WANG Zhen1，ZHOU Hong3，5，6(1. College of Pharmacy， Linyi University， Shandong Linyi 276005， China; 2. College of Life Science and Biopharmaceutics， Shenyang Pharmaceutical University， Liaoning Benxi 117004， China; 3. Shandong Fuyang Energy Conservation Technology Co.， Ltd.， Shandong Linyi 276005， China; 4. Dept. of Pharmaceutical Engineering， College of Chemistry and Pharmacy， Guangxi Normal University， Guangxi Guilin 541004， China; 5. College of Chemistry and Molecular Engineering， Qingdao University of Science and Technology， Shandong Qingdao 266042， China; 6. Key Laboratory of Optic-electric Sensing and Analytical Chemistry for Life Science， Ministry of Education， Shandong Qingdao 266042， China)
ABSTRACT OBJECTIVE： To prepare Chelerythrine (CHE) solid dispersion (SD)， optimize the formulation technology， characterize its preparation and investigate its in vitro antioxidant activity. METHODS： The content of CHE in SD was determined by UV spectrophotometry. Based on single factor tests， using the product yield as index， using preparation method， carrier material type， carrier material proportion (drug-carrier material mass ratio) as factors， the formulation technology of SD was optimized by L9(34) orthogonal test and validated. Based on solubility and accumulative dissolution determination， the product was characterized with thermal analyssis， X-ray diffraction and scanning electron microscope. Using ascorbic acid as positive control， in vitro antioxidant activity of the product was determined by DPPH method. RESULTS： The linear range of CHE was 2.4-5.6 μg/mL; quantitation limit and detection limit were 0.066 9， 0.022 1 μg/mL; RSDs of precision， stability and reproducibility tests were all lower than 2%; recoveries were 97.50%-99.25%(RSD<1%，n=3). The optimal preparation technology included using PEG 6000 as carrier material， carrier material ratio of 1 ∶ 3， prepared by solvent method. Three batches of CHE-PEG-SD were prepared. Verification test results showed that the accumulative dissolution of CHE-PEG-SD was (61.72±0.67)% at 15 min， and the yield was (99.04±0.83)%. The results of characterization showed that after CHE-PEG-SD prepared， its solubility (3.725 mg/mL) and accumulative dissolution (61.25%， 15 min) were higher than CHE raw material [0.098 mg/mL， 6.24% (180 min)]. The endothermic peak and crystal absorption peak moved or even disappeared compared with raw material and the carrier material， and CHE was uniformly dispersed in the carrier material as an amorphous state. Results of in vitro antioxidation test showed that different concentration of CHE-PEG-SD showed certain ability of DPPH free radical scavenging， and the IC50 was 0.124 mg/mL， higher than 0.041 mg/mL of ascorbic acid. CONCLUSIONS： Established content determination method is simple and accurate. The optimal SD formulation technology is stable and feasible. The solubility of prepared CHE-PEG-SD increases， and the dissolution in vitro increases， showing certain in vitro oxidation resistance., 百拇医药(王云 李平平 高振珅 张晓萍 王振 周宏)
DOI 10.6039/j.issn.1001-0408.2020.09.07
摘 要 目的：制备白屈菜红碱(CHE)固体分散体(SD)，优化其处方工艺，并对所制产品进行表征和体外抗氧化活性考察。方法：采用紫外分光光度法测定SD中CHE的含量;在单因素试验的基础上，以产品收率为指标，以制备方法、载体材料种类、载体比例(药物-载体材料质量比)为考察因素，采用L9(34)正交试验优化SD的处方工艺并进行验证。在检测溶解度和累积溶出度的基础上，采用热分析法、X-射线衍射法和扫描电子显微镜等技术对产品进行物相表征;以抗坏血酸为阳性对照，采用1，1-二苯基-2-三硝基苯肼法(DPPH)测定产品的体外抗氧化活性。结果：CHE检测质量浓度的线性范围为2.4～5.6 μg/mL，定量限、检测限分别为0.066 9、0.022 1 μg/mL;精密度、稳定性、重复性试验的RSD均小于2%，加样回收率为97.50%～99.25%(RSD<1%，n=3)。最优制备工艺是以聚乙二醇6000(PEG 6000)为载体、载体比例为1 ∶ 3，采用溶剂法制备。按最优工艺制得3批CHE-PEG-SD，验证试验结果显示，其在15 min时的累积溶出度为(61.72±0.67)%，收率为(99.04±0.83)%。表征结果显示，制成CHE-PEG-SD后，其溶解度(3.725 mg/mL)和累积溶出度(61.72%，15 min)均高于CHE原料药[0.098 mg/mL，6.24%(180 min)];其吸热峰、晶体吸收峰均较原料药和载体有所移动甚至消失，CHE以非晶态均匀分散于载体中。体外抗氧化试验结果显示，不同质量浓度的CHE-PEG-SD均具有一定的DPPH自由基清除能力，半数抑制浓度为0.124 mg/mL，但高于抗坏血酸的0.041 mg/mL。结论：所建含量测定方法简便、准确;优化的SD处方工艺稳定、可行;所制CHE-PEG-SD的溶解度增大，体外溶出增多，且具有一定的体外抗氧化活性。
关键词 白屈菜红碱;固体分散体;工艺优化;体外溶出;表征;抗氧化活性
Preparation of Chelerythrine Solid Dispersion and Study on Its Physicochemical Properties and Antioxidant Activity
WANG Yun1，2，3，LI Pingping1，3，4，GAO Zhenshen1，ZHANG Xiaoping1，3，WANG Zhen1，ZHOU Hong3，5，6(1. College of Pharmacy， Linyi University， Shandong Linyi 276005， China; 2. College of Life Science and Biopharmaceutics， Shenyang Pharmaceutical University， Liaoning Benxi 117004， China; 3. Shandong Fuyang Energy Conservation Technology Co.， Ltd.， Shandong Linyi 276005， China; 4. Dept. of Pharmaceutical Engineering， College of Chemistry and Pharmacy， Guangxi Normal University， Guangxi Guilin 541004， China; 5. College of Chemistry and Molecular Engineering， Qingdao University of Science and Technology， Shandong Qingdao 266042， China; 6. Key Laboratory of Optic-electric Sensing and Analytical Chemistry for Life Science， Ministry of Education， Shandong Qingdao 266042， China)
ABSTRACT OBJECTIVE： To prepare Chelerythrine (CHE) solid dispersion (SD)， optimize the formulation technology， characterize its preparation and investigate its in vitro antioxidant activity. METHODS： The content of CHE in SD was determined by UV spectrophotometry. Based on single factor tests， using the product yield as index， using preparation method， carrier material type， carrier material proportion (drug-carrier material mass ratio) as factors， the formulation technology of SD was optimized by L9(34) orthogonal test and validated. Based on solubility and accumulative dissolution determination， the product was characterized with thermal analyssis， X-ray diffraction and scanning electron microscope. Using ascorbic acid as positive control， in vitro antioxidant activity of the product was determined by DPPH method. RESULTS： The linear range of CHE was 2.4-5.6 μg/mL; quantitation limit and detection limit were 0.066 9， 0.022 1 μg/mL; RSDs of precision， stability and reproducibility tests were all lower than 2%; recoveries were 97.50%-99.25%(RSD<1%，n=3). The optimal preparation technology included using PEG 6000 as carrier material， carrier material ratio of 1 ∶ 3， prepared by solvent method. Three batches of CHE-PEG-SD were prepared. Verification test results showed that the accumulative dissolution of CHE-PEG-SD was (61.72±0.67)% at 15 min， and the yield was (99.04±0.83)%. The results of characterization showed that after CHE-PEG-SD prepared， its solubility (3.725 mg/mL) and accumulative dissolution (61.25%， 15 min) were higher than CHE raw material [0.098 mg/mL， 6.24% (180 min)]. The endothermic peak and crystal absorption peak moved or even disappeared compared with raw material and the carrier material， and CHE was uniformly dispersed in the carrier material as an amorphous state. Results of in vitro antioxidation test showed that different concentration of CHE-PEG-SD showed certain ability of DPPH free radical scavenging， and the IC50 was 0.124 mg/mL， higher than 0.041 mg/mL of ascorbic acid. CONCLUSIONS： Established content determination method is simple and accurate. The optimal SD formulation technology is stable and feasible. The solubility of prepared CHE-PEG-SD increases， and the dissolution in vitro increases， showing certain in vitro oxidation resistance., 百拇医药(王云 李平平 高振珅 张晓萍 王振 周宏)
参见：首页 > 中医药 > 中药专业 > 中草药汇编 > 中药大典 > 全草类 > 白屈菜