水溶性辅料对非诺贝特与羟丙基-β-环糊精包合物的影响
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摘要
目的研究水溶性辅料对非诺贝特与羟丙基-β-环糊精之间包合作用的影响。方法采用相溶解度法进行非诺贝特的增溶实验,并用机械球磨法制备非诺贝特/羟丙基-β-环糊精的包合物以及含有少量水溶性辅料的三元体系。通过差示扫描量热法(DSC)、X射线衍射法(XRD)、红外光谱(FTIR)、核磁共振氢谱(~1H-NRM)、体外溶出及稳定性试验等对所制备的包合物进行验证。结果二元及三元体系的体外溶出率和稳定性结果表明,加入甘露醇、羟丙甲纤维素(HPMC)和泊洛沙姆188均能提高包合物的稳定性常数和包合率。此外,HPMC的加入可以使包合物更加稳定,体外溶出速率也有所提高。结论加入少量适当的水溶性辅料可以增强羟丙基-β-环糊精与药物的包合效果,并且形成更稳定的三元体系。
OBJECTIVE To study the effect of water-soluble materials on the inclusion complex of fenofibrate and hydroxypropyl-β-cyclodextrin. METHODS The inclusion complex of fenofibrate/hydroxypropyl-β-cyclodextrin and the ternary system containing water-soluble materials were obtained by ball milling. The inclusion complex was characterized by differential scanning calorimetry( DSC),powder X-ray diffractometry( XRD),Fourier-transformed infrared spectrophotometry( FTIR),~1H-NMR spectroscopy,as well as in vitro dissolution and stability test. RESULTS The stability tests and in vitro dissolution results showed that the addition of water-soluble materials could improve the stability constant and inclusion efficiency of the inclusion complex. Moreover,the addition of hydroxypropyl methylcellulose( HPMC) could result in a more stable complex and the in vitro dissolution rate of complex was also increased. CONCLUSION The addition of appropriate water-soluble materials could enhance the inclusion efficiency of hydroxypropyl-β-cyclodextrin with drugs and form a more stable system.
OBJECTIVE To study the effect of water-soluble materials on the inclusion complex of fenofibrate and hydroxypropyl-β-cyclodextrin. METHODS The inclusion complex of fenofibrate/hydroxypropyl-β-cyclodextrin and the ternary system containing water-soluble materials were obtained by ball milling. The inclusion complex was characterized by differential scanning calorimetry( DSC),powder X-ray diffractometry( XRD),Fourier-transformed infrared spectrophotometry( FTIR),~1H-NMR spectroscopy,as well as in vitro dissolution and stability test. RESULTS The stability tests and in vitro dissolution results showed that the addition of water-soluble materials could improve the stability constant and inclusion efficiency of the inclusion complex. Moreover,the addition of hydroxypropyl methylcellulose( HPMC) could result in a more stable complex and the in vitro dissolution rate of complex was also increased. CONCLUSION The addition of appropriate water-soluble materials could enhance the inclusion efficiency of hydroxypropyl-β-cyclodextrin with drugs and form a more stable system.
引文
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[2]BUCH P,MEYER C,LANGGUTH P.Improvement of the wettability and dissolution of fenofibrate compacts by plasma treatment[J].Int J Pharm,2011,416(1):49-54.
[3]HUANG Q P,WANG J X,ZHANG Z B,et al.Preparation of ultrafine fenofibrate powder by solidification process from emulsion[J].Int J Pharm,2009,368(1-2):160-164.
[4]ZHONG L,ZHU X,LUO X,et al.Dissolution properties and physical characterization of telmisartan-chitosan solid dispersions prepared by mechanochemical activation[J].Aaps Pharmscitech,2013,14(2):541-550.
[5]ALOISIO C,ANTIMISIARIS S G,LONGHI M R.Liposomes containing cyclodextrins or meglumine to solubilize and improve the bioavailability of poorly soluble drugs[J].J Mol Liq,2017,229:106-113.
[6]PEREIRA R A,ANCONI C P A,NASCIMENTOJR X S,et al.Stability and spatial arrangement of the 2,4-dichlorophenoxyacetic acid andβ-cyclodextrin inclusion compound:a theoretical study[J].Chem Phys Lett,2015,633(1):158-162.
[7]DU F,MENG H,XU K,et al.CPT loaded nanoparticles based on beta-cyclodextrin-grafted poly(ethylene glycol)/poly(L-glutamic acid)diblock copolymer and their inclusion complexes with CPT[J].Colloid Surface B,2014,113(1):230-236.
[8]FRACETO L F,GRILLO R.Cyclodextrin inclusion complexes loaded in particles as drug carrier systems[J].Curr Top Med Chem,2014,14(4):518-525.
[9]SANTOS C I A V,TEIJEIRO C,RIBEIRO A C F,et al.Drug delivery systems:study of inclusion complex formation for ternary caffeine-β-cyclodextrin-water mixtures from apparent molar volume values at 298.15 K and 310.15 K[J].J Mol Liquids,2016,223:209-216.
[10]SILVA C V,BARBOSA J A,FERRAZ M S,et al.Molecular modeling and cytotoxicity of diffractaic acid:HP-β-CD inclusion complex encapsulated in microspheres[J].Int J Biol Macromol,2016,92:494-503.
[11]JUN S W,KIM M S,KIM J S,et al.Preparation and characterization of simvastatin/hydroxypropyl-β-cyclodextrin inclusion complex using supercritical antisolvent(sas)process[J].Eur JPharm Biopharm,2007,66(3):413-421.
[12]BANCHERO M,MANNA L.Investigation of the piroxicam/hydroxypropyl-β-cyclodextrin inclusion complexation by means of a supercritical solvent in the presence of auxiliary agents[J].J Supercrit Fluid,2011,57(3):259-266.
[13]PATEL A R,VAVIA P R.Preparation and evaluation of taste masked famotidine formulation using drug/beta-cyclodextrin/polymer ternary complexation approach[J].Aaps Pharmscitech,2008,9(2):544-550.
[14]MOREIRA M P,ANDRADE G R S,ARAUJO M V G D,et al.Ternary cyclodextrin polyurethanes containing phosphate groups:synthesis and complexation of ciprofloxacin[J].Carbohyd Polym,2016,151:557-564.
[15]LIAO Y,ZHANG X,LI C,et al.Inclusion complexes of HP-β-cyclodextrin with agomelatine:preparation,characterization,mechanism study and in vivo evaluation[J].Carbohyd Polym,2016,147:415-425.
[16]RIBEIRO L,LOFTSSON T,FERREIRA D,et al.Investigation and physicochemical characterization of vinpocetine-sulfobutyl etherβ-cyclodextrin binary and ternary complexes[J].Chem Pharm Bull,2003,51(8):914-922.
[17]DANCIU C,SOICA C,OLTEAN M,et al Genistein in 1∶1 inclusion complexes with ramified cyclodextrins:theoretical,physicochemical and biological evaluation[J].Int J Mol Sci,2014,15(2):1962-1982.
[18]OL'KHOVICH M V,SHARAPOVA A V,LAVRENOV S N,et al.Inclusion complexes of hydroxypropyl-β-cyclodextrin with novel cytotoxic compounds:solubility and thermodynamic properties[J].Fluid Phase Equilibr,2014,384:68-72.
[19]SAUCEAU M,RODIER E,FAGES J.Preparation of inclusion complex of piroxicam with cyclodextrin by using supercritical carbon dioxide[J].J Supercrit Fluid,2008,47(2):326-332.
[20]LINARES M S,LONGHI M R.Effects of hydroxypropyl-beta-cyclodextrin on the chemical stability of a naphthoquinone in aqueous solutions[J].Pharmazie Die,2003,58(1):32.
[21]LIU B,ZHAO J,LIU Y,et al.Physicochemical properties of the inclusion complex of puerarin and glucosyl-β-cyclodextrin[J].JAgr Food Chem,2013,61(2):12501-12507.