微型化介质研磨法制备塞来昔布纳米混悬剂
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摘要
目的:采用微型化介质研磨法制备塞来昔布(CB)纳米混悬剂(CB-NS),增加其溶出度。方法:以平均粒径(PS)、多分散度指数(PDI)和稳定系数(SI)为指标,采用Box-Behnken设计-效应面法优化CB-NS的工艺参数,并对其进行扫描电镜观察、X射线衍射分析及体外溶出度考察。结果:最优工艺参数为氧化锆珠子5.0 ml,研磨速度1 300 r/min,研磨时间8.0 h;以最优工艺参数制得的CB-NS的PS为(307±10) nm,PDI为0.281±0.013,SI为0.71±0.04;扫描电镜结果与激光粒度仪测试结果接近;CB-NS中CB的结晶度有一定程度减弱;CB-NS的体外溶出度明显高于原料药和物理混合物。结论:微型化介质研磨法可成功制备CB-NS,且工艺简单,稳定可行,可为CB-NS的制备提供新的参考。
OBJECTIVE: To prepare celecoxib(CB) nanosuspension(CB-NS) by miniaturized medium grinding method, so as to increase its dissolution. METHODS: The average particle size(PS), polydispersity index(PDI) and stability coefficient(SI) were set as indices, Box-Behnken method was adopted to optimize the technological parameter of CB-NS and conducted scanning electron microscope(SEM) observation, X-ray diffraction analysis and vitro dissolution inspection. RESULTS: The optimal technological parameter was 5.0 ml of zirconia bead, grinding speed of 1 300 r/min and grinding time of 8.0 h; the PS of obtained CB-NS was(307±10) nm, with PDI of 0.281±0.013 and SI of 0.71±0.04; the results of SEM were close to those of laser particle analyzer; the crystallinity of CB in CB-NS had a certain weakening; the vitro dissolution of CB-NS was significantly higher than that of bulk drug and physical mixture. CONCLUSIONS: The miniaturized medium grinding method can successfully prepare CB-NS, with simple, stable and feasible process, which can provide a new reference for the preparation of CB-NS.
OBJECTIVE: To prepare celecoxib(CB) nanosuspension(CB-NS) by miniaturized medium grinding method, so as to increase its dissolution. METHODS: The average particle size(PS), polydispersity index(PDI) and stability coefficient(SI) were set as indices, Box-Behnken method was adopted to optimize the technological parameter of CB-NS and conducted scanning electron microscope(SEM) observation, X-ray diffraction analysis and vitro dissolution inspection. RESULTS: The optimal technological parameter was 5.0 ml of zirconia bead, grinding speed of 1 300 r/min and grinding time of 8.0 h; the PS of obtained CB-NS was(307±10) nm, with PDI of 0.281±0.013 and SI of 0.71±0.04; the results of SEM were close to those of laser particle analyzer; the crystallinity of CB in CB-NS had a certain weakening; the vitro dissolution of CB-NS was significantly higher than that of bulk drug and physical mixture. CONCLUSIONS: The miniaturized medium grinding method can successfully prepare CB-NS, with simple, stable and feasible process, which can provide a new reference for the preparation of CB-NS.
引文
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[13] 安宁,谢鹏,王敏,等.塞来昔布载药胶束的制备与大鼠体内药动学研究[J].解放军药学学报,2018,34(1):30-33.
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[15] 黄婷,林巧平,钱勇,等.塞来昔布纳米晶体的制备与表征[J].中国医药工业杂志,2015,46(4):358-363.
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[2] Kim HI,Park SY,Park SJ,et al.Development and Evaluation of a Reconstitutable Dry Suspension to Improve the Dissolution and Oral Absorption of Poorly Water-Soluble Celecoxib[J].Pharmaceutics,2018,10(3):140.
[3] Hokuto D,Nomi T,Kawaguchi C,et al.The Administration of Cele-coxib as an Analgesic after Liver Resection Is Safe[J].Dig Surg,2017,34(2):108-113.
[4] Mammoto T,Fujie K,Mamizuka N,et al.Effects of postoperative administration of celecoxib on pain management in patients after total knee arthroplasty:study protocol for an open-label randomized controlled trial[J].Trials,2016,17:45.
[5] Zhou F,Du Y,Huang W,et al.The efficacy and safety of early initi-ation of preoperative analgesia with celecoxib in patients under-went arthroscopic knee surgery:A randomized,controlled study[J].Medi-cine(Baltimore),2017,96(42):e8234.
[6] Lainé AL,Price D,Davis J,et al.Enhanced oral delivery of celecoxib via the development of a supersaturable amorphous formulation utili-sing mesoporous silica and co-loaded HPMCAS[J].Int J Pharm,2016,512(1):118-125.
[7] Van N,Hien,Park,et al.Improving the dissolution rate of a poorly water-soluble drug via adsorption onto pharmaceutical diluents[J].J Drug Deliv Sci Tec,2016,35:146-154.
[8] Sudhakar B,Nagajyothi K,Murthy KV.Nanosuspensions as a vers-atile carrier based drug delivery system-an overview[J].Curr Drug Deliv,2014,11(3):299-305.
[9] Lu Y,Qi J,Dong X,et al.The in vivo fate of nanocrystals[J].Drug Discov Today,2017,22(4):744-750.
[10] Romero GB,Keck CM,Müller RH.Simple low-cost miniaturization approach for pharmaceutical nanocrystals production[J].Int J Ph-arm,2016,501(1-2):236-244.
[11] 申宝德,连王权,沈成英,等.微型化介质研磨法制备难溶性黄酮类化合物纳米混悬剂[J].中草药,2017,48(21):4413-4418.
[12] Dong X,Niu Y,Ding Y,et al.Formulation and Drug Loading Feat-ures of Nano-Erythrocytes[J].Nanoscale Res Lett,2017,12(1):202.
[13] 安宁,谢鹏,王敏,等.塞来昔布载药胶束的制备与大鼠体内药动学研究[J].解放军药学学报,2018,34(1):30-33.
[14] 吴铭芳,许文佳,祖元刚,等.桦木酸纳米粒的制备与表征[J].中国药房,2017,28(31):4445-4448.
[15] 黄婷,林巧平,钱勇,等.塞来昔布纳米晶体的制备与表征[J].中国医药工业杂志,2015,46(4):358-363.
[16] 刘阳,谢锦,许俊男,等.药物固体纳米晶体稳定性关键影响因素的研究进展[J].中国医药工业杂志,2018,49(8):1073-1082.