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微环境pH对吲哚美辛固体分散体溶出行为的影响及评价

曹杰, 朱志凌, 袁梦, 柯学

曹杰, 朱志凌, 袁梦, 柯学. 微环境pH对吲哚美辛固体分散体溶出行为的影响及评价[J]. 中国药科大学学报, 2019, 50(6): 686-693. DOI: 10.11665/j.issn.1000-5048.20190608
引用本文: 曹杰, 朱志凌, 袁梦, 柯学. 微环境pH对吲哚美辛固体分散体溶出行为的影响及评价[J]. 中国药科大学学报, 2019, 50(6): 686-693. DOI: 10.11665/j.issn.1000-5048.20190608
CAO Jie, ZHU Zhiling, YUAN Meng, KE Xue. Effect and evaluation of microenvironment pH on dissolution behavior of indomethacin solid dispersion[J]. Journal of China Pharmaceutical University, 2019, 50(6): 686-693. DOI: 10.11665/j.issn.1000-5048.20190608
Citation: CAO Jie, ZHU Zhiling, YUAN Meng, KE Xue. Effect and evaluation of microenvironment pH on dissolution behavior of indomethacin solid dispersion[J]. Journal of China Pharmaceutical University, 2019, 50(6): 686-693. DOI: 10.11665/j.issn.1000-5048.20190608

微环境pH对吲哚美辛固体分散体溶出行为的影响及评价

Effect and evaluation of microenvironment pH on dissolution behavior of indomethacin solid dispersion

  • 摘要: 研究和评价微环境pH对无定型固体分散体溶出行为的影响及其可能的机制。以吲哚美辛(IND)为模型药物,Kollidon®; VA64为载体材料,通过热熔挤出法制备IND无定型固体分散体(SD),使用差示扫描量热法(DSC)与X射线粉末衍射法(PXRD)进行表征。考察微环境pH调节剂葡甲胺(MEG)加入前后对固体分散体在不同溶出介质中溶出行为的影响。设计实验从溶出介质浸润速度、微环境pH、药物溶出后再结晶等多角度评价溶出行为的差异。结果发现,MEG提供的碱性微环境加速IND的溶出,但是在不同溶出介质中,pH调节剂产生的微环境强度和持续时间、局部药物再结晶情况和介质浸润粉末速度均存在明显差异,且以上多种因素共同作用影响固体分散体中药物的溶出行为。
    Abstract: In this study, the effect of pH regulator meglumine(MEG)on the dissolution behavior of indomethacin(IND)amorphous solid dispersions was evaluated. The amorphous solid dispersion was prepared by hot-melt extrusion using IND and Kollidon® VA64 at a weight ratio of 1∶4, and extrudates were characterized using differential scanning calorimetry(DSC)and X-ray powder diffraction(PXRD). The dissolution behaviors of solid dispersions with or without MEG were investigated in three kinds of pH media. The effect of infiltration rate of media, microenvironmental pH(pHM)and recrystallization of drugs on drug dissolution were evaluated by designing the appropriate experiments. The results showed that the presence of MEG could accelerate the dissolution of IND from solid dispersions through providing an alkaline microenvironment, but in different dissolution media, the intensity and duration of alkaline microenvironment, recrystallization of local drug molecules and infiltration rate of media showed an obvious difference, and the above factors simultaneously affected the dissolution behavior of drugs from solid dispersions.
  • [1] Allesφ M,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.
    [2] Pore Y,Shinde V,Rao J.Physical stabilization of amorphous itraconazole in solid dispersions for improved dissolution profile[J].J App Pharm Sci,2016:037-044.
    [3] Dahan A,Beig A,Ioffe-Dahan V,et al.The twofold advantage of the amorphous form as an oral drug delivery practice for lipophilic compounds:increased apparent solubility and drug flux through the intestinal membrane[J].AAPS J,2013,15(2):347-353.
    [4] Wan SX,Sun YQ,Qi XX,et al.Improved bioavailability of poorly water-soluble drug curcumin in cellulose acetate solid dispersion[J].AAPS PharmSciTech,2012,13(1):159-166.
    [5] Shi XJ,Gao J,Liu ZL,et al.Enhanced dissolution of famotidine by cocrystal formation with tartaric acid and maleic acid[J].J China Pharm Univ(中国药科大学学报),2013,44(2):124-126.
    [6] Yoshida T,Kurimoto I,Yoshihara K,et al.Aminoalkyl methacrylate copolymers for improving the solubility of tacrolimus.I:evaluation of solid dispersion formulations[J].Int J Pharm,2012,428(1/2):18-24.
    [7] Chen YL,Liao JB,Liang YZ,et al.Characterization of solid dispersions of Patchouli alcohol with different polymers:effects on the inhibition of reprecipitation and the improvement of dissolution rate[J].Drug Dev Ind Pharm,2015,41(3):436-444.
    [8] Dengale SJ,Grohganz H,Rades T,et al.Recent advances in co-amorphous drug formulations[J].Adv Drug Deliv Rev,2016,100:116-125.
    [9] Vasconcelos T,Sarmento B,Costa P.Solid dispersions as strategy to improve oral bioavailability of poor water soluble drugs[J].Drug Discov Today,2007,12(23/24):1068-1075.
    [10] Dhumal RS,Kelly AL,York P,et al.Cocrystalization and simultaneous agglomeration using hot melt extrusion[J].Pharm Res,2010,27(12):2725-2733.
    [11] Dierickx L,Van Snick B,Monteyne T,et al.Co-extruded solid solutions as immediate release fixed-dose combinations[J].Eur J Pharm Biopharm,2014,88(2):502-509.
    [12] Patel PS,Raval JP,Patel HV.Review on the pharmaceutical applications of hot melt extruder[J].Asian J Pharm Clin Res,2010,3(2):80-83.
    [13] Patil H,Tiwari RV,Repka MA.Hot-melt extrusion:from theory to application in pharmaceutical formulation[J].AAPS PharmSciTech,2016,17(1):20-42.
    [14] Betageri G.Enhancement of dissolution of glyburide by solid dispersion and lyophilization techniques[J].Int J Pharm,1995,126(1/2):155-160.
    [15] Chiou WL,Riegelman S.Pharmaceutical applications of solid dispersion systems[J].J Pharm Sci,1971,60(9):1281-1302.
    [16] Xia YL,Yuan M,Deng YY,et al.Different effects of silica added internal or external on in vitro dissolution of indomethacin hot-melt extrudates[J].Int J Pharm,2017,534(1/2):272-278.
    [17] Srinarong P,Faber JH,Visser MR,et al.Strongly enhanced dissolution rate of fenofibrate solid dispersion tablets by incorporation of superdisintegrants[J].Eur J Pharm Biopharm,2009,73(1):154-161.
    [18] Yamashita S,Fukunishi A,Higashino H,et al.Design of supersaturable formulation of telmisartan with pH modifier:in vitro study on dissolution and precipitation[J].J Pharm Invest,2017,47(2):163-171.http://dx.doi.org/10.1007/s40005-017-0310-3.
    [19] Tran PH,Tran HT,Lee BJ.Modulation of microenvironmental pH and crystallinity of ionizable telmisartan using alkalizers in solid dispersions for controlled release[J].J Control Release,2008,129(1):59-65.
    [20] Bi MD,Kyad A,Kiang YH,et al.Enhancing and sustaining AMG 009 dissolution from a matrix tablet via microenvironmental pH modulation and supersaturation[J].AAPS PharmSciTech,2011,12(4):1157-1162.
    [21] Doherty C,York P.Microenvironmental pH control of drug dissolution[J].Int J Pharm,1989,50(3):223-232.
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出版历程
  • 刊出日期:  2019-12-24

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