芪苓制剂超微粉的稳定性研究
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摘要
本研究以黄芪甲苷及白术内酯Ш为主要检测指标。采用影响因素试验分析影响芪苓制剂超微粉稳定性的因素,寻找适合芪苓制剂超微粉的包装方法及廉价有效的药物稳定剂和抗氧化剂。采用加速稳定性试验确定芪苓制剂超微粉的有效期。试验结果如下:
1、建立了ELSD-HPLC测定芪苓制剂超微粉中黄芪甲苷含量的方法。芪苓制剂超微粉用甲醇提取,后用液-液萃取纯化。色谱条件:色谱柱Eclipse XDB-C18,流动相为乙腈-水(30:70),柱温25℃。测得芪苓制剂超微粉中黄芪甲苷含量为545.79μg·g -1。
2、建立了DAD-HPLC测定芪苓制剂超微粉中白术内酯Ⅲ含量的方法。芪苓制剂超微粉用甲醇提取,后用固相萃取小柱纯化。色谱条件:色谱柱ZORBAX SB-C18,流动相为甲醇-乙腈-水(30:30:40),检测波长220 nm,柱温30℃。测得芪苓制剂超微粉中白术内酯Ⅲ含量为97.14μg·g -1。
3、影响因素试验
⑴高温试验:芪苓制剂超微粉于60oC条件下放置10d,定时取样检测。结果显示,温度对芪苓制剂超微粉的稳定性影响较大。10天内,黄芪甲苷的含量降至66.54%;白术内酯Ⅲ的含量降至12.68%。
⑵高湿试验:芪苓制剂超微粉于25oC、RH90%±5%条件下放置10d,定时取样检测。结果显示,湿度度对芪苓制剂超微粉的稳定性影响较大。10天内,黄芪甲苷的含量降至47.50%,白术内酯Ⅲ的含量降至79.80%。
⑶强光照试验:芪苓制剂超微粉于光照4500±500XL条件下放置10d,定时取样检测。结果显示,光照对芪苓制剂超微粉的稳定性影响均较大。10天内,黄芪甲苷的含量降至74.20%,白术内酯Ⅲ的含量降至65.43%。
4、稳定剂、抗氧化剂及包装及的选择
⑴包装的选择:将芪苓制剂超微粉的不同包装品于60oC加速条件下放置10 d,于5 d,10 d取样检测。结果表明,真空包装与密封包装效果无显著差异;PET-铝箔-PE复合包装袋优于LDPE尼龙复合包装袋。
⑵稳定剂及抗氧化剂的选择:将含有不同抗氧化剂及稳定剂的芪苓制剂超微粉于60oC加速条件下放置5 d,取样检测。结果如下:稳定剂PVP可以有效抑制芪苓制剂超微粉的褐变,减慢黄芪甲苷含量下降速度、减缓白术内酯Ш的含量变化;异VC钠可以有效抑制芪苓制剂超微粉的褐变,减缓白术内酯Ш的含量变化。稳定剂优化试验结果表明芪苓制剂超微粉中异VC钠添加量在2%～5%,PVP添加量在3%～5%较为适宜。
5、加速稳定性试验
含有2%异VC钠、3% PVP芪苓制剂超微粉由PET-铝箔-PE复合袋密封包装于40oC、RH75%的加速条件下放置6个月。至6月时黄芪甲苷的含量约降至89%;白术内酯Ш的含量约降至93%。故此,以黄芪甲苷、白术内酯Ш为检测指标时,芪苓制剂超微粉的有效期约为24个月。
AstragalosideⅣand ActractylenolideⅢwere the main indexes in this study. Effect-factors test was used to Analyze the factors affecting the stability of ultra micro powder of Qi-Ling medicament, and to search appropriate packaging, and cheap and effective drugs stabilizer and antioxidant for ultra micro powder of Qi-Ling medicament. The validity period of medicament of Qi-Ling ultra micro powder was determined by accelerated stability test. The results are as follows:
1 A test method by ELSD-HPLC for AstragalosideⅣin ultra micro powder of Qi-Ling medicament was established. AstragalosideⅣwas extracted with methanol, then purified by liquid-liquid extraction from ultra micro powder of Qi-Ling medicament. The optimal conditions of separation and detection were achieved on a C18 analytical column with an mobile phase consisting of acetonitrile-water (30:70). The column temperature was maintained at 25℃. The content of AstragalosideⅣin ultra micro powder of Qi-Ling medicament was 545.79μg·g -1.
2 A test method by DAD-HPLC for ActractylenolideⅢin ultra micro powder of Qi-Ling medicament was established. ActractylenolideⅢwas extracted with methanol, then purified by SPE from ultra micro powder of Qi-Ling medicament. The optimal conditions of separation and detection were achieved on a C18 analytical column with a mobile phase consisting of methanol-acetonitrile-water (30:30:40) at the flow-rate of 1mL·min-1. The detection wavelength was 220nm. The column temperature was maintained at 30℃. The content of ActractylenolideⅢin ultra micro powder of Qi-Ling medicament was 97.14μg·g -1.
3 Effect-factors test
⑴High-temperature test: Ultra micro powder of Qi-Ling medicament was put in the conditions of 60oC for 10 days, sampled and measured timing. The results showed that, the temperature seriously effected the stability of ultra micro powder of Qi-Ling medicament. The content of AstragalosideⅣdeduced to 66.54%, and the content of ActractylenolideⅢdecreased to 12.68% within 10 days.
⑵High-humidity test: Ultra micro powder of Qi-Ling medicament was put in the conditions of 25oC, RH90%±5% for 10 days, sampled and measured timing. The results showed that: High-humidity extremely effected the stability of ultra micro powder of Qi-Ling medicament. The content of AstragalosideⅣdeduced to 47.50%, the content of ActractylenolideⅢdeceased to 79.80%.
⑶High-intensity light test: Ultra micro powder of Qi-Ling medicament was put in the conditions of 4500±500XL for 10 days, sampled and measured timing. The results showed that: the light exceedingly effected the stability of ultra micro powder of Qi-Ling medicament. The content of AstragalosideⅣdeduced to74.20%, the content of ActractylenolideⅢdecreased to 65.43% within 10 days.
4 The choice of packaging, stabilizer and antioxidant
⑴Packaging choice: Different bulk product of ultra micro powder of Qi-Ling medicament was put in the condition of 60oC for 10 days, and sampled and measured at the 5th, the 10th.The results showed that the effects of vacuum-packed and sealed package were no significantly different; PET-Al-PE Strip Packaging was superior to LDPE nylon Strip Packaging.
⑵Stabilizer and antioxidant choice: Ultra micro powder of Qi-Ling medicament with different stabilizer and antioxidants was put in the condition of 60oC for 5 days, sampled and measured. The results showed that PVP could effectively inhibit brown of ultra micro powder of Qi-Ling medicament, and the content of AstragalosideⅣand ActractylenolideⅢchanged; D-Sodium isoascorbiate could effectively inhibit ultra micro powder of Qi-Ling medicament browning, inhibit content of ActractylenolideⅢchanged. D-Sodium isoascorbiate was befittingly appended in 2%～5% and PVP was befittingly appended in 3%～5%, determined by stabilizer optimal experiment.
5 Accelerated stability test
Ultra micro powder of Qi-Ling medicament with 2% D-Sodium isoascorbiate, 3% PVP, packaged by PET-Al-PE Strip Packaging was put the accelerated condition of 40oC, RH75% for 6 months. The content of AstragalosideⅣdeduced to about 89% and the content of ActractylenolideⅢdecreased to about 93% at the 6th month. Therefore, using AstragalosideⅣand ActractylenolideⅢas the main indexes, the validity period of ultra micro powder of Qi-Ling medicament was about 24 months.
1、建立了ELSD-HPLC测定芪苓制剂超微粉中黄芪甲苷含量的方法。芪苓制剂超微粉用甲醇提取,后用液-液萃取纯化。色谱条件:色谱柱Eclipse XDB-C18,流动相为乙腈-水(30:70),柱温25℃。测得芪苓制剂超微粉中黄芪甲苷含量为545.79μg·g -1。
2、建立了DAD-HPLC测定芪苓制剂超微粉中白术内酯Ⅲ含量的方法。芪苓制剂超微粉用甲醇提取,后用固相萃取小柱纯化。色谱条件:色谱柱ZORBAX SB-C18,流动相为甲醇-乙腈-水(30:30:40),检测波长220 nm,柱温30℃。测得芪苓制剂超微粉中白术内酯Ⅲ含量为97.14μg·g -1。
3、影响因素试验
⑴高温试验:芪苓制剂超微粉于60oC条件下放置10d,定时取样检测。结果显示,温度对芪苓制剂超微粉的稳定性影响较大。10天内,黄芪甲苷的含量降至66.54%;白术内酯Ⅲ的含量降至12.68%。
⑵高湿试验:芪苓制剂超微粉于25oC、RH90%±5%条件下放置10d,定时取样检测。结果显示,湿度度对芪苓制剂超微粉的稳定性影响较大。10天内,黄芪甲苷的含量降至47.50%,白术内酯Ⅲ的含量降至79.80%。
⑶强光照试验:芪苓制剂超微粉于光照4500±500XL条件下放置10d,定时取样检测。结果显示,光照对芪苓制剂超微粉的稳定性影响均较大。10天内,黄芪甲苷的含量降至74.20%,白术内酯Ⅲ的含量降至65.43%。
4、稳定剂、抗氧化剂及包装及的选择
⑴包装的选择:将芪苓制剂超微粉的不同包装品于60oC加速条件下放置10 d,于5 d,10 d取样检测。结果表明,真空包装与密封包装效果无显著差异;PET-铝箔-PE复合包装袋优于LDPE尼龙复合包装袋。
⑵稳定剂及抗氧化剂的选择:将含有不同抗氧化剂及稳定剂的芪苓制剂超微粉于60oC加速条件下放置5 d,取样检测。结果如下:稳定剂PVP可以有效抑制芪苓制剂超微粉的褐变,减慢黄芪甲苷含量下降速度、减缓白术内酯Ш的含量变化;异VC钠可以有效抑制芪苓制剂超微粉的褐变,减缓白术内酯Ш的含量变化。稳定剂优化试验结果表明芪苓制剂超微粉中异VC钠添加量在2%～5%,PVP添加量在3%～5%较为适宜。
5、加速稳定性试验
含有2%异VC钠、3% PVP芪苓制剂超微粉由PET-铝箔-PE复合袋密封包装于40oC、RH75%的加速条件下放置6个月。至6月时黄芪甲苷的含量约降至89%;白术内酯Ш的含量约降至93%。故此,以黄芪甲苷、白术内酯Ш为检测指标时,芪苓制剂超微粉的有效期约为24个月。
AstragalosideⅣand ActractylenolideⅢwere the main indexes in this study. Effect-factors test was used to Analyze the factors affecting the stability of ultra micro powder of Qi-Ling medicament, and to search appropriate packaging, and cheap and effective drugs stabilizer and antioxidant for ultra micro powder of Qi-Ling medicament. The validity period of medicament of Qi-Ling ultra micro powder was determined by accelerated stability test. The results are as follows:
1 A test method by ELSD-HPLC for AstragalosideⅣin ultra micro powder of Qi-Ling medicament was established. AstragalosideⅣwas extracted with methanol, then purified by liquid-liquid extraction from ultra micro powder of Qi-Ling medicament. The optimal conditions of separation and detection were achieved on a C18 analytical column with an mobile phase consisting of acetonitrile-water (30:70). The column temperature was maintained at 25℃. The content of AstragalosideⅣin ultra micro powder of Qi-Ling medicament was 545.79μg·g -1.
2 A test method by DAD-HPLC for ActractylenolideⅢin ultra micro powder of Qi-Ling medicament was established. ActractylenolideⅢwas extracted with methanol, then purified by SPE from ultra micro powder of Qi-Ling medicament. The optimal conditions of separation and detection were achieved on a C18 analytical column with a mobile phase consisting of methanol-acetonitrile-water (30:30:40) at the flow-rate of 1mL·min-1. The detection wavelength was 220nm. The column temperature was maintained at 30℃. The content of ActractylenolideⅢin ultra micro powder of Qi-Ling medicament was 97.14μg·g -1.
3 Effect-factors test
⑴High-temperature test: Ultra micro powder of Qi-Ling medicament was put in the conditions of 60oC for 10 days, sampled and measured timing. The results showed that, the temperature seriously effected the stability of ultra micro powder of Qi-Ling medicament. The content of AstragalosideⅣdeduced to 66.54%, and the content of ActractylenolideⅢdecreased to 12.68% within 10 days.
⑵High-humidity test: Ultra micro powder of Qi-Ling medicament was put in the conditions of 25oC, RH90%±5% for 10 days, sampled and measured timing. The results showed that: High-humidity extremely effected the stability of ultra micro powder of Qi-Ling medicament. The content of AstragalosideⅣdeduced to 47.50%, the content of ActractylenolideⅢdeceased to 79.80%.
⑶High-intensity light test: Ultra micro powder of Qi-Ling medicament was put in the conditions of 4500±500XL for 10 days, sampled and measured timing. The results showed that: the light exceedingly effected the stability of ultra micro powder of Qi-Ling medicament. The content of AstragalosideⅣdeduced to74.20%, the content of ActractylenolideⅢdecreased to 65.43% within 10 days.
4 The choice of packaging, stabilizer and antioxidant
⑴Packaging choice: Different bulk product of ultra micro powder of Qi-Ling medicament was put in the condition of 60oC for 10 days, and sampled and measured at the 5th, the 10th.The results showed that the effects of vacuum-packed and sealed package were no significantly different; PET-Al-PE Strip Packaging was superior to LDPE nylon Strip Packaging.
⑵Stabilizer and antioxidant choice: Ultra micro powder of Qi-Ling medicament with different stabilizer and antioxidants was put in the condition of 60oC for 5 days, sampled and measured. The results showed that PVP could effectively inhibit brown of ultra micro powder of Qi-Ling medicament, and the content of AstragalosideⅣand ActractylenolideⅢchanged; D-Sodium isoascorbiate could effectively inhibit ultra micro powder of Qi-Ling medicament browning, inhibit content of ActractylenolideⅢchanged. D-Sodium isoascorbiate was befittingly appended in 2%～5% and PVP was befittingly appended in 3%～5%, determined by stabilizer optimal experiment.
5 Accelerated stability test
Ultra micro powder of Qi-Ling medicament with 2% D-Sodium isoascorbiate, 3% PVP, packaged by PET-Al-PE Strip Packaging was put the accelerated condition of 40oC, RH75% for 6 months. The content of AstragalosideⅣdeduced to about 89% and the content of ActractylenolideⅢdecreased to about 93% at the 6th month. Therefore, using AstragalosideⅣand ActractylenolideⅢas the main indexes, the validity period of ultra micro powder of Qi-Ling medicament was about 24 months.
引文
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