辛伐他汀与阿司匹林共无定形复合物的制备
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摘要
目的制备辛伐他汀-阿司匹林共无定形复合物,并考察其溶出情况。方法利用溶剂蒸发法制备不同摩尔比的辛伐他汀与阿司匹林样品;采用差示扫描量热分析法(DSC)和粉末X射线衍射法(PXRD)对所制不同摩尔比的辛伐他汀-阿司匹林样品进行表征测定;利用HPLC法对辛伐他汀-阿司匹林共无定形样品进行溶出度测定。结果 DSC和PXRD结果表明,在不同摩尔比的辛伐他汀-阿司匹林样品中,只有摩尔比为2∶1的辛伐他汀-阿司匹林复合物为共无定形药物;溶出测定结果表明,共无定形样品中辛伐他汀的溶出度相对于原料药辛伐他汀有很大提高,但阿司匹林的溶出度没有明显提高。结论辛伐他汀-阿司匹林共无定形复合物的制备,为临床多药联合使用、减少患者用药品种数和提高药物治疗效果提供了新思路和理论基础。
Objective To prepare simvastatin-aspirin co-amorphous and investigate their dissolution.Methods Simvastatin-aspirin coamorphous complex in different molar ratios was prepared by solvent evaporation technique.The physicochemical properties of coamorphous complex were characterized by differential scanning calorimetry(DSC)and powder X-ray diffraction methods(PXRD).The dissolution of the co-amorphous was investigated by HPLC.Results DSC and PXRD analysis suggested that simvastatin and aspirin with the mole ratio of 2∶1presented as an amorphous substance in different mole ratios of simvastatin and aspirin samples.The accumulated dissolution rate of simvastatin in simvastatin-aspirin co-amorphous complex was improved,but aspirins rate was not.Conclusion The preparation of simvastatin-aspirin co-amorphous complex provided new strategies for decreasing the numbers of drugs used in patients,reducing drug interactions and improving the patients medication compliance.
Objective To prepare simvastatin-aspirin co-amorphous and investigate their dissolution.Methods Simvastatin-aspirin coamorphous complex in different molar ratios was prepared by solvent evaporation technique.The physicochemical properties of coamorphous complex were characterized by differential scanning calorimetry(DSC)and powder X-ray diffraction methods(PXRD).The dissolution of the co-amorphous was investigated by HPLC.Results DSC and PXRD analysis suggested that simvastatin and aspirin with the mole ratio of 2∶1presented as an amorphous substance in different mole ratios of simvastatin and aspirin samples.The accumulated dissolution rate of simvastatin in simvastatin-aspirin co-amorphous complex was improved,but aspirins rate was not.Conclusion The preparation of simvastatin-aspirin co-amorphous complex provided new strategies for decreasing the numbers of drugs used in patients,reducing drug interactions and improving the patients medication compliance.
引文
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[15]李扬,惠静.阿司匹林联合头孢哌酮对急性脑卒中患者生化指标的影响[J].西北药学杂志,2018,33(5):668-671.
[16]陈娟,郭慧慧,张建军,等.共无定形辛伐他汀-格列齐特的理化性质[J].中国药科大学学报,2015,46(3):301-308.
[17]Dengale S J,Ranjan O P,Hussen S S,et al.Preparation and characterization of co-amorphous ritonavir-indomethacin systems by solvent evaporation technique:improved dissolution behavior and physical stability without evidence of intermolecular interactions[J].Eur J Pharm Sci,2014,62(4):57-64.
[18]L9bmann K,Grohganz H,Laitinen R,et al.Amino acids as coamorphous stabilizers for poorly water soluble drugspart 1:preparation,stability and dissolution enhancement[J].Eur J Pharm Biopharm,2013,85(3):873-881.
[19]Shayanfar A,Ghavimi H,Hamishehkar H,et al.Coamorphous atorvastatin calcium to improve its physicochemical and pharmacokinetic properties[J].J Pharm Pharm Sci,2013,16(4):577-587.
[20]申亚静,覃蕾,衡伟利,等.他达拉非-达泊西汀共无定形物的形成及其溶出度与稳定性的评价[J].药学学报,2018,53(7):1162-1168.
[21]Laitinen R,L9bmann K,Strachan C J,et al.Emerging trends in the stabilization of amorphous drugs[J].Int J Pharm,2013,453(1):65-79.
[2] Plosker G L,McTavish D.Simvastatin.A reappraisal of its pharmacology and therapeutic efficacy in hypercholeste-rolaemia[J].Drugs,1995,50(2):334-363.
[3] Lu Q,Zografi G.Phase behavior of binary and ternary amorphous mixtures containing indomethacin,citric acid,and PVP[J].Pharm Res,1998,15(8):1202-1206.
[4] Di L,Fish P V,Mano T.Bridging solubility between drug discovery and development[J].Drug Discov Today,2012,9(17):486-495.
[5] L9bmann K,Laitinen R,Grohganz H,et al.Coamorphous drug systems enhanced physical stability and dissolution rate of indomethacin and naproxen[J].Mol Pharm,2011,8(5):1919-1928.
[6]郭慧慧,苗娜娜,李腾飞,等.共无定形药物——新型单相无定形二元体系[J].化学进展,2014,26(2):478-486.
[7] Soica C,Oprean C,Borcan F,et al.The synergistic biologic activity of oleanolic and ursolic acids in complex with hydroxypropyl-γ-cyclodextrin[J].Molecules,2014,19(4):4924-4940.
[8] Qian S,Heng W L,Wei Y F,et al.Coamorphous lurasidone hydrochloride-saccharin with charge-assisted hydrogen bonding interaction shows improved physical stability and enhanced dissolution with pH-independent solubility behavior[J].Cryst Growth Des,2015,15(6):2920-2928.
[9] Qian S,Li Z,Heng W L,et al.Charge-assisted intermolecular hydrogen bond formed in coamorphous system is important to relieve the pH-dependent solubility behavior of lurasidone hydrochloride[J].RSC Adv,2016,6(108):106396-106412.
[10]L9bmann K,Strachan C,Grohganz H,et al.Co-amorphous simvastatin and glipizide combinations show improved physical stability without evidence of intermolecular interactions[J].Eur J Pharm Biopharm,2012,81(1):159-169.
[11]Lobmann K,Laitinen R,Grohganz H,et al.Coamorphous drug systems:enhanced physical stability and dissolution rate of indomethacin and naproxen[J].Mol Pharm,2011,8(5):1919-1928.
[12]Cattaneo M,Angelo A D,Canciani M T,et al.Effect of oral aspirin on plasma levels of vitamin K-dependent clotting factors-studies in healthy volunteers[J].Thromb Haemost,1988,59(3):540.
[13]Buczko W,Mogielnicki A,Kramkowski K,et al.Aspirin and the fibrinolytic response[J].Thromb Res,2003,110(5):331-334.
[14]AllesM,Chieng N,Rehder S,et al.Enhanced dissolution rate and synchronized release of drugs in binary systems through formulation:amorphous naproxen-cimetidine mixtures prepared by mechanical activation[J].J Control Release,2009,136(1):45-53.
[15]李扬,惠静.阿司匹林联合头孢哌酮对急性脑卒中患者生化指标的影响[J].西北药学杂志,2018,33(5):668-671.
[16]陈娟,郭慧慧,张建军,等.共无定形辛伐他汀-格列齐特的理化性质[J].中国药科大学学报,2015,46(3):301-308.
[17]Dengale S J,Ranjan O P,Hussen S S,et al.Preparation and characterization of co-amorphous ritonavir-indomethacin systems by solvent evaporation technique:improved dissolution behavior and physical stability without evidence of intermolecular interactions[J].Eur J Pharm Sci,2014,62(4):57-64.
[18]L9bmann K,Grohganz H,Laitinen R,et al.Amino acids as coamorphous stabilizers for poorly water soluble drugspart 1:preparation,stability and dissolution enhancement[J].Eur J Pharm Biopharm,2013,85(3):873-881.
[19]Shayanfar A,Ghavimi H,Hamishehkar H,et al.Coamorphous atorvastatin calcium to improve its physicochemical and pharmacokinetic properties[J].J Pharm Pharm Sci,2013,16(4):577-587.
[20]申亚静,覃蕾,衡伟利,等.他达拉非-达泊西汀共无定形物的形成及其溶出度与稳定性的评价[J].药学学报,2018,53(7):1162-1168.
[21]Laitinen R,L9bmann K,Strachan C J,et al.Emerging trends in the stabilization of amorphous drugs[J].Int J Pharm,2013,453(1):65-79.