淫羊藿素-泊洛沙姆188固体分散体的制备及溶出度研究
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摘要
目的:制备淫羊藿素-泊洛沙姆188固体分散体以提高淫羊藿素的溶出度。方法:以泊洛沙姆188为载体,采用熔融法制备固体分散体。通过体外溶出度比较,考察了载体泊洛沙姆188的用量(淫羊藿素-泊洛沙姆188质量之比为5∶1、3∶1、2∶1、1∶1、1∶3、1∶5、1∶7、1∶9、1∶11、1∶13、1∶15、1∶17、1∶19、1∶27、1∶31)、熔融温度(60、70、80℃)、冷却温度(-20、0、20℃)对固体分散体中淫羊藿溶出度的影响;同时比较了淫羊藿素原料药及其物理混合物、固体分散体的体外溶出度以证实固体分散体的形成。结果:所制固体分散体的淫羊藿素溶出度在一定程度上随载体比例增加而增加,当淫羊藿素与载体之比为1∶17~1∶27时淫羊藿素在120min时的溶出度均在90%以上;熔融温度、冷却温度经综合分析后分别确定为60、0℃;在溶出30 min时,固体分散体的溶出度是物理混合物的1.5倍。结论:制备的固体分散体显著提高了淫羊藿素的溶出度。
OBJECTIVE:To prepare icaritin-poloxamer 188 solid dispersions in order to increase the dissolution rate of icaritin.METHODS:With poloxamer 188 as the carrier,melting method was used to prepare solid dispersions.By comparing the in vitro dissolution rates,the effects of the content of poloxamer 188(the ratios of icaritin to poloxamer 188 were 5 ∶ 1,3 ∶ 1,2 ∶ 1,1 ∶ 1,1 ∶3,1 ∶ 5,1 ∶ 7,1 ∶ 9,1 ∶ 11,1 ∶ 13,1 ∶ 15,1 ∶ 17,1 ∶ 19,1 ∶ 27 and 1 ∶ 31),melting temperature(60,70 and 80 ℃)and cooling temperature(-20,0 and 20 ℃)on the dissolution rate of icaritin in the solid dispersions were investigated,and the in vitro dissolution rates of icaritin in its active pharmaceutical ingredient,physical mixture and solid dispersions were compared to confirm the formation of the solid dispersions.RESULTS:The dissolution rate of icaritin in the prepared solid dispersions increased to some extent as the proportion of the carrier increased.When the ratio of icaritin to the carrier was 1 ∶ 17-1 ∶ 27,the dissolution rate of icaritin at120 min was above 90%.Where melting temperature and cooling temperature were respectively determined as 60 ℃ and 0 ℃ after comprehensive comparison,the dissolution rate of icaritin in the solid dispersions was 1.5 times as much as that in the physical mixture at 30 min.CONCLUSIONS:The prepared solid dispersion has a significantly higher dissolution rate of icaritin.
OBJECTIVE:To prepare icaritin-poloxamer 188 solid dispersions in order to increase the dissolution rate of icaritin.METHODS:With poloxamer 188 as the carrier,melting method was used to prepare solid dispersions.By comparing the in vitro dissolution rates,the effects of the content of poloxamer 188(the ratios of icaritin to poloxamer 188 were 5 ∶ 1,3 ∶ 1,2 ∶ 1,1 ∶ 1,1 ∶3,1 ∶ 5,1 ∶ 7,1 ∶ 9,1 ∶ 11,1 ∶ 13,1 ∶ 15,1 ∶ 17,1 ∶ 19,1 ∶ 27 and 1 ∶ 31),melting temperature(60,70 and 80 ℃)and cooling temperature(-20,0 and 20 ℃)on the dissolution rate of icaritin in the solid dispersions were investigated,and the in vitro dissolution rates of icaritin in its active pharmaceutical ingredient,physical mixture and solid dispersions were compared to confirm the formation of the solid dispersions.RESULTS:The dissolution rate of icaritin in the prepared solid dispersions increased to some extent as the proportion of the carrier increased.When the ratio of icaritin to the carrier was 1 ∶ 17-1 ∶ 27,the dissolution rate of icaritin at120 min was above 90%.Where melting temperature and cooling temperature were respectively determined as 60 ℃ and 0 ℃ after comprehensive comparison,the dissolution rate of icaritin in the solid dispersions was 1.5 times as much as that in the physical mixture at 30 min.CONCLUSIONS:The prepared solid dispersion has a significantly higher dissolution rate of icaritin.
引文
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[2]牟关敏,蒲文臣,周敏,等.淫羊藿素的合成[J].有机化学,2013,33(6):1 298.
[3]包宇,杨建雄,孙润广.淫羊藿苷与脱水淫羊藿素的体外抗氧化研究[J].陕西师范大学学报:自然科学版,2012,40(3):67.
[4]贾晓斌,钱浅,孙娥,等.淫羊藿黄酮药动学研究进展[J].中成药,2012,34(11):2 193.
[5]刘凯杰,李超.淫羊藿药理研究进展[J].亚热带植物科学,2014,43(2):181.
[6]刘玉亮,梁广胜,魏强强,等.淫羊藿总黄酮及淫羊藿体外抗骨肉瘤的研究[J].中成药,2013,35(10):2 072.
[7]刘海培,孟繁华,郭继芬,等.淫羊藿素在大鼠体内的药动学研究[J].中国药学杂志,2010,45(7):539.
[8]陈周全,张宁.固体分散体技术在中药制剂中的应用概况[J].中国药房,2012,23(15):1 427.
[9]李标.固体分散体在药剂学中的应用[J].中国药房,2009,20(10):790.
[10]呼自顺.盐酸小檗碱泊洛沙姆188固体分散体的制备[J].中国药房,2010,21(11):990.
[11]张立.淫羊藿素血药浓度检测方法研究[J].湖北中医杂志,2013,35(12):66.
[12]刘海培,孟繁华,郭继芬,等.HPLC-MS/MS法分析大鼠体内淫羊藿素葡糖醛酸结合物[J].质谱学报,2010,31(6):376.
[13]Van den Mooter G,Wuyts M,Blaton N,et al.Physical stabilization of amorphous ketoconazole in solid dispersions with polyvinylpyrrolidone K25[J].Eur J Pharm Sci,2001,12(3):261.
[14]Weuts I,Kempen D,Six K,et al.Evaluation of different calorimetric methods to determine the glass transition temperature and molecular mobility below Tg for amorphous drugs[J].Int J Pharm,2003,259(1/2):17.