马钱子碱包合物微孔渗透泵控释片的制备
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摘要
目的制备马钱子碱包合物微孔渗透泵控释片。方法制备包合物以提高马钱子碱溶解度及体外溶出度,再将其制成微孔渗透泵控释片。在单因素试验基础上,以促渗聚合物(聚氧乙烯WRS-N-10)用量、包衣增重、致孔剂(聚乙二醇400)用量、增塑剂(邻苯二甲酸二乙酯)用量为影响因素,累积释放度为评价指标,正交试验优化处方。结果最佳处方为聚氧乙烯WRS-N-10用量10 mg,包衣增重3.5%,聚乙二醇400用量30%,邻苯二甲酸二乙酯用量25%,12 h内累积释放度88.44%。微孔渗透泵控释片体外释药行为符合零级模型,在12 h内恒速释药。结论马钱子碱包合物微孔渗透泵控释片处方合理,释药稳定。
AIM To prepare the microporous osmotic pump controlled-release tablets of brucine inclusion compounds.METHODS The inclusion compounds were prepared to increase solubility and in vitro dissolution rate of brucine, followed by the preparation of osmotic pump controlled-release tablets. With permeation enhancing polymer(polyoxyethylene WRS-N-10) consumption, coating weight gain, pore-forming agent(polyethylene glycol 400) consumption and plasticizer(diethyl phthalate) consumption as influencing factors, accumulative release rate as an evaluation index, the formulation was optimized by orthogonal test on the basis of single factor test.RESULTS The optimal formulation was determined to be 10 mg for polyoxyethylene WRS-N-10 consumption, 3.5% for coating weight gain, 30% for polyethylene glycol 400 consumption, and 25% for diethyl phthalate consumption, the accumulative release rate was 88.44% within 12 h. Releasing drug at a constant speed within 12 h, the in vitro drug release behaviors of microporous osmotic pump controlled-release tablets accorded with zero-order model.CONCLUSION The microporous osmotic pump controlled-release tablets of brucine inclusion compounds exhibit reasonable formulation and stable drug release.
AIM To prepare the microporous osmotic pump controlled-release tablets of brucine inclusion compounds.METHODS The inclusion compounds were prepared to increase solubility and in vitro dissolution rate of brucine, followed by the preparation of osmotic pump controlled-release tablets. With permeation enhancing polymer(polyoxyethylene WRS-N-10) consumption, coating weight gain, pore-forming agent(polyethylene glycol 400) consumption and plasticizer(diethyl phthalate) consumption as influencing factors, accumulative release rate as an evaluation index, the formulation was optimized by orthogonal test on the basis of single factor test.RESULTS The optimal formulation was determined to be 10 mg for polyoxyethylene WRS-N-10 consumption, 3.5% for coating weight gain, 30% for polyethylene glycol 400 consumption, and 25% for diethyl phthalate consumption, the accumulative release rate was 88.44% within 12 h. Releasing drug at a constant speed within 12 h, the in vitro drug release behaviors of microporous osmotic pump controlled-release tablets accorded with zero-order model.CONCLUSION The microporous osmotic pump controlled-release tablets of brucine inclusion compounds exhibit reasonable formulation and stable drug release.
引文
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[7] 王周丽,贝永燕,朱爱军,等.蛇床子素β-环糊精包合物分散片的制备及大鼠体内药动学研究[J].中成药,2012,34(10):1887-1892.
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[11] 吴先闯,郝海军,宋晓勇,等.白芍总苷微孔渗透泵片的研制及体外同步释放性研究[J].中药材,2016,39(2):363-366.
[12] 邓向涛,郝海军,韩茹,等.黄芩素包合物单层渗透泵片制备工艺研究[J].第二军医大学学报,2015,36(5):513-517.
[13] 郭留城,杜利月,郝海军,等.青藤碱固体脂质纳米粒凝胶骨架缓释片的制备及处方优化[J].中国医院药学杂志,2018,38(18):1893-1897.
[14] 邓向涛,郝海军,王思寰,等.蛇床子素包合物凝胶骨架片的制备及体外释放[J].时珍国医国药,2016,27(7):1644-1646.
[15] 曹伶俐,刘刚,胡彬,等.槲皮素固体脂质纳米粒凝胶骨架缓释片制备工艺研究[J].中药材,2016,39(6):1369-1371.
[16] 杨宁辉,付金芳,曹伶俐.蛇床子素渗透泵控释片制备工艺的优化及其体外释药行为[J].中成药,2018,40(9):1954-1958.
[17] 郝海军,贾幼智,韩茹,等.坎地沙坦酯固体分散体单层渗透泵片的制备[J].中国新药杂志,2015,24(5):570-575.
[18] 吴先闯,郝海军,宋晓勇,等.白藜芦醇单层渗透泵片的制备工艺研究及评价[J].中药材,2015,38(8):1732-1735.
[19] 周昌妮,冯青云,徐如冰,等.星点设计-效应面法优化复方葛黄微孔渗透泵片的处方组成[J].中国实验方剂学杂志,2016,22(10):20-24.
[20] 陈晓莉,李永吉,王录娜,等.HPLC法测定马钱子缓释片中士的宁与马钱子碱[J].哈尔滨商业大学学报(自然科学版),2013,29(4):390-393.
[21] 王洪珍,张炜煜.益髓通经缓释颗粒的质量控制[J].中国医院药学杂志,2013,33(16):1361-1364.
[2] 邹莹,裘涛,杨峰.炙马钱子对实验性自身免疫性重症肌无力大鼠免疫调节机制研究[J].中华中医药杂志,2015,30(8):2994-2998.
[3] Yin W, Wang T S, Yin F Z, et al. Analgesic and anti-inflammatory properties of brucine and brucine N-oxide extracted from seeds of Strychnos nux-vomica[J]. J Ethnopharmacol, 2003, 88(2-3): 205-214.
[4] 何晓玮,范晓萍,钟涛,等.马钱子碱新型给药系统治疗类风湿性关节炎的研究进展[J].中华中医药学刊,2015,33(12):2908-2911.
[5] 管庆霞,郭玉岩,赵权涛,等.正交实验法优选马钱子碱固体脂质纳米粒制备工艺[J].时珍国医国药,2012,23(12):3063-3064.
[6] 潘娅,张燕君,谢昭朐,等.马钱子碱-β-环糊精包合物的制备及表征[J].中成药,2013,35(8):1805-1808.
[7] 王周丽,贝永燕,朱爱军,等.蛇床子素β-环糊精包合物分散片的制备及大鼠体内药动学研究[J].中成药,2012,34(10):1887-1892.
[8] Cui H M, Wu F L. Pharmacokinetics of Eb and its hydroxypropyl-β-cyclodextrin inclusion complex in rats[J]. J Chin Pharm Sci, 2010, 19(1): 52-58.
[9] 吴小娟,马凤森,郑高利.马钱子吲哚类生物碱毒性研究进展[J].中药药理与临床,2016,32(6):231-235.
[10] 吴先闯,郝海军,宋晓勇,等.槲皮素包合物微孔渗透泵片制备工艺[J].中成药,2015,37(6):1205-1209.
[11] 吴先闯,郝海军,宋晓勇,等.白芍总苷微孔渗透泵片的研制及体外同步释放性研究[J].中药材,2016,39(2):363-366.
[12] 邓向涛,郝海军,韩茹,等.黄芩素包合物单层渗透泵片制备工艺研究[J].第二军医大学学报,2015,36(5):513-517.
[13] 郭留城,杜利月,郝海军,等.青藤碱固体脂质纳米粒凝胶骨架缓释片的制备及处方优化[J].中国医院药学杂志,2018,38(18):1893-1897.
[14] 邓向涛,郝海军,王思寰,等.蛇床子素包合物凝胶骨架片的制备及体外释放[J].时珍国医国药,2016,27(7):1644-1646.
[15] 曹伶俐,刘刚,胡彬,等.槲皮素固体脂质纳米粒凝胶骨架缓释片制备工艺研究[J].中药材,2016,39(6):1369-1371.
[16] 杨宁辉,付金芳,曹伶俐.蛇床子素渗透泵控释片制备工艺的优化及其体外释药行为[J].中成药,2018,40(9):1954-1958.
[17] 郝海军,贾幼智,韩茹,等.坎地沙坦酯固体分散体单层渗透泵片的制备[J].中国新药杂志,2015,24(5):570-575.
[18] 吴先闯,郝海军,宋晓勇,等.白藜芦醇单层渗透泵片的制备工艺研究及评价[J].中药材,2015,38(8):1732-1735.
[19] 周昌妮,冯青云,徐如冰,等.星点设计-效应面法优化复方葛黄微孔渗透泵片的处方组成[J].中国实验方剂学杂志,2016,22(10):20-24.
[20] 陈晓莉,李永吉,王录娜,等.HPLC法测定马钱子缓释片中士的宁与马钱子碱[J].哈尔滨商业大学学报(自然科学版),2013,29(4):390-393.
[21] 王洪珍,张炜煜.益髓通经缓释颗粒的质量控制[J].中国医院药学杂志,2013,33(16):1361-1364.