HPMCAS/PVP K30胡椒碱双载体无定型固体分散体的制备及其体外溶出测定
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摘要
为提高胡椒碱(Piperine,Pip)的体外溶出,本文对Pip的双载体无定型态固体分散体制备技术进行研究。将醋酸羟丙基甲基纤维素琥珀酸酯(HPMC-AS)的3种异构体(HPMC-AS-HF、HPMC-AS-MF、HPMCAS-LF,分别简称为HF、MF和LF)和聚乙烯吡咯烷酮PVP K30(K30)按一定比例混合作为载体,并通过超饱和测试测定其对Pip溶液超饱和度的影响。使用溶剂法制备Pip双载体无定型态固体分散体,并运用差示扫描量热法(DSC)和红外光谱(IR)对Pip双载体固体分散体进行表征。实验结果显示K30/HF、K30/LF、K30/MF 3种组合均对Pip有一定的增溶作用,HF与MF可以提高溶液的超饱和度。当双载体固体分散体载药量为10%时,其溶出速度和稳定性按比例顺序为K30/HF>K30/MF>K30/LF。当MF/HF比例为1∶1或4∶1时效果最佳。随着MF占比增大,双载体固体分散体的溶出速度加快,稳定性下降。因此,双载体无定型态固体分散体对于维持胡椒碱的超饱和作用和提高体外溶出度都有显著效果。
In order to improve the in vitro dissolution of piperine(Pip),the preparation technology of Pip doublecarrier amorphous solid dispersion was studied. Three isomers of hydroxypropyl methylcellulose acetate succinate(HPMC-AS)(HPMC-AS-HF,HPMC-AS-MF,HPMC-AS-LF,referred to as HF,MF and LF,respectively)and polyvinyl pyrrolidone PVP K30(K30) were mixed as a carrier in a certain ratio,and its effect on the super saturation of Pip solution was determined by super saturation test. The Pip dual-carrier amorphous solid dispersion was prepared by solvent method,and the Pip dual-carrier solid dispersion was characterized by differential scanning calorimetry(DSC) and infrared spectroscopy(IR). The experiment results showed that the combination of K30/HF,K30/LF and K30/MF all had a certain solubilization effect on Pip,and HF and MF could increase the super saturation of the solution. When the dual carrier solid dispersion was loaded at 10%,the dissolution rate and stability were in the order of K30/HF > K30/MF > K30/LF. When the MF/HF ratio was 1∶1 or 4∶1,the effect was the best. As the MF ratio increased,the dissolution rate of the dual carrier solid dispersion increased and the stability decreased. Therefore,the dual-carrier amorphous solid dispersion has a significant effect on maintaining the super saturation of pip and improving the dissolution in vitro.
In order to improve the in vitro dissolution of piperine(Pip),the preparation technology of Pip doublecarrier amorphous solid dispersion was studied. Three isomers of hydroxypropyl methylcellulose acetate succinate(HPMC-AS)(HPMC-AS-HF,HPMC-AS-MF,HPMC-AS-LF,referred to as HF,MF and LF,respectively)and polyvinyl pyrrolidone PVP K30(K30) were mixed as a carrier in a certain ratio,and its effect on the super saturation of Pip solution was determined by super saturation test. The Pip dual-carrier amorphous solid dispersion was prepared by solvent method,and the Pip dual-carrier solid dispersion was characterized by differential scanning calorimetry(DSC) and infrared spectroscopy(IR). The experiment results showed that the combination of K30/HF,K30/LF and K30/MF all had a certain solubilization effect on Pip,and HF and MF could increase the super saturation of the solution. When the dual carrier solid dispersion was loaded at 10%,the dissolution rate and stability were in the order of K30/HF > K30/MF > K30/LF. When the MF/HF ratio was 1∶1 or 4∶1,the effect was the best. As the MF ratio increased,the dissolution rate of the dual carrier solid dispersion increased and the stability decreased. Therefore,the dual-carrier amorphous solid dispersion has a significant effect on maintaining the super saturation of pip and improving the dissolution in vitro.
引文
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[2]DOUCETTE C D,HILCHIE A L,LIWSKI R,et al.Adietary phyto-chemical,inhibits angiogenesis[J].J Nutr Biochem,2013(24):231e239.
[3]LI S,WANG C,WANG M W,et al.Antidepressant like effects of piperine in chronic mild stress treated mice and its possible mechanisms[J].Life Sciences,2007,80(15):1373-1381.
[4]VAIBHAV K,SHRIVASTAVA P,JAVED H,et al.Piperine suppresses cerebral ischemia-reperfusion-induced inflammation through the repression of COX-2,NOS-2,and NF-κB in middle cerebral artery occlusion rat model.[J].Molecular and Cellular Biochemistry,2012,367(1/2):73-84.
[5]ATAL N,BEDI K L.Bioenhancers:Revolutionary concept to market[J].Journal of Ayurveda and Integrative Medicine,2010,1(2):96-99.
[6]SINGH S,JAMWAL S,KUMAR P.Piperine enhances the protective effect of curcumin against 3-NP induced neurotoxicity:Possible neurotransmitters modulation mechanism[J].Neurochemical Research,2015,40(8):1758-1766.
[7]PACHAURI M,GUPTA E D,GHOSH P C.Piperine loaded PEG-PLGA nanoparticles:Preparation,characterization and targeted delivery for adjuvant breast cancer chemotherapy[J].Journal of Drug Delivery Science and Technology,2015,29:269-282.
[8]SHIN S C.Studies on hydrophobic drug-soluble carrier coprecitates(Ⅱ)[J].Archives of Pharmacal Research,1979,2(1):49-64.
[9]KARAVAS E,KTISTIS G,XENAKIS A,et al.Effect of hydrogen bonding interactions on the release mechanism of felodipine from nanodispersions with polyvinylpyrrolidone[J].European Journal of Pharmaceutics and Biopharmaceutics,2006,63(2):103-114.
[10]谢燕,邹珊珊,李国文,等.醋柳黄酮固体分散体的制备研究[J].中草药,2010,41(9):1469-1473.
[11]宗莉,肖衍字,陈伶俐.用二元载体固体分散技术提高尼索地平溶出度和调节溶出速率[J].中国药学杂志2005,40(3):203-206.
[12]张烨,郑颖,土一涛.复方丹参制剂的质量研究[J].中成药,2009,31(12):1855-1860.
[13]BOGHRA R J,KOTHAWADE P C,BELGAMWAR VS,et al.Solubility,dissolution rate and bioavailability enhancement of irbesartan by solid dispersion technique[J].Chem Pharm Bull(Tokyo),2011,59(4):438-41.
[14]上海医药工业设计院药物制剂教研部.药用辅料应用技术[M].第2版.北京:中国医药科技出版社,2002:72.
[15]李鑫,史金儒,羊梦诗,等.胡椒生物碱提取,几何结构以及红外光谱的研究[J].光谱学与光谱分析,2016,36(7):2082-2088.