他克莫司固体分散体的制备及肠吸收研究
Preparation and gastrointestinal absorption kinetics of tacrolimus solid dispersion
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摘要: 制备他克莫司固体分散体，提高他克莫司的溶解度、促进药物吸收。采用不同的水溶性载体制备固体分散体，通过体外溶出度实验筛选出最优处方，采用扫描电子显微镜法(SEM)、X射线衍射法(XRD)、差示扫描量热法(DSC)对最优处方的固体分散体进行结构表征，并通过大鼠在体胃肠吸收实验研究其在胃肠道吸收特性。体外溶出结果表明，采用水溶性载体羟丙甲纤维素(HPMC E3)制备的固体分散体溶出速率最快；SEM、XRD和DSC结果表明，他克莫司以无定形形态分布于载体HPMC E3中；大鼠在体胃肠吸收实验结果表明，以HPMC E3为载体制备的固体分散体在胃肠道吸收比原料药显著增加。故以HPMC E3为载体制备他克莫司固体分散体可以有效提高溶解度，促进药物吸收。Abstract: To prepare tacrolimus solid dispersion to increase the solubility and bioavailability of tacrolimus. Tacrolimus solid dispersions were prepared by different water-soluble carriers, which were evaluated by in vitro drug dissolutions to select the optimal formulation. The optimal tacrolimus solid dispersion was evaluated by scanning electron microscopy(SEM), X-ray diffraction(XRD)and differential scanning calorimetry(DSC), and its gastrointestinal absorption kinetics was studied in rats. The results showed that tacrolimus solid dispersion with HPMC E3 as carrier had the fastest dissolution rate. SEM, XRD and DSC studies indicated that tacrolimus was distributed within the carrier HPMC E3 in amorphous form. Gastrointestinal absorption experiments in rats demonstrated that the optimal formulation remarkably increased oral absorption of tacrolimus. These results demonstrate that a novel tacrolimus solid dispersion with HPMC E3 as carrier may be an advantageous dosage form of tacrolimus, boosting the solubility and absorption in gastrointestinal tract.
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Keywords:
- tacrolimus /
- solid dispersion /
- HPMC /
- dissolution /
- gastrointestinal absorption
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[1] Liu F, Wei JF, Meng L, et al. New development in macrolide immunosuppressant[J].Chin New Drugs J(中国新药杂志),2014,22(1):61-66. [2] Liu YS,Gao S,Ke X,et al.Recent research advances in solid dispersions of poorly soluble drugs[J].Prog Pharm Sci(药学进展),2013,37(4):166-173. [3] Yan F,Ke X,Ping QN,et al.Preparation of baicalein solid dispersions and oral bioavailability in rats[J].J China Pharm Univ(中国药科大学学报),2008,39(5):406-411. [4] Zhang Q, Zhang MX, Zhang J, et al. Studies on the intestinal absorption kinetics of tacrolimus in rats[J].Chin Hosp Pharm J(中国医院药学杂志),2010,30(8):639-642. [5] Veloxis Pharma Inc.Modified release tacrolimus compositions:CN,1859910A[P].2006-11-08[2016-03-11] . [6] Arik D, Brady T, Gordon L, et al. Segmental-dependent membrane permeability along the intestine following oral drug administration:evaluation of a triple single-pass intestinal perfusion(TSPIP)approach in the rat[J].Eur J Pharm Sci,2009,36:320-329. [7] Ying J,Lyu Y,Du GH.New development in amorphous drug[J].Acta Pharm Sin(药学学报),2009,44(5):443-448. [8] Astellas Pharma Inc.Tacrolimus sustained release pharmaceutical composition:EP,2119442A[P].2009-11-18[2016-03-11] .
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