目的研究氯雷他定自微乳制剂自乳化能力和体内药动学特征。方法绘制三元相图，考察最优处方的粒径、Zeta电位、稳定性。比较氯雷他定自微乳制剂与市售片剂的体外溶出度。采用LC-MS/MS测定Beagle犬血药浓度，与市售片剂比较，研究氯雷他定自微乳制剂的相对生物利用度。结果氯雷他定自微乳制剂加水乳化后的平均粒径为（28.15±1.65）nm。以蒸馏水为溶出介质，15min溶出80%以上。比格犬体内药动学结果表明，自微乳制剂的最大血药浓度ρmax是片剂的9倍，并且AUC0-t是片剂的5.3倍。结论自微乳制剂可以显著提高氯雷他定的体外溶出度和体内吸收。
Abstract
OBJECTIVE To evaluate the dissolution behavior in vitro and the pharmacokinetic behavior of loratadine self-microemulsifying formulation in Beagle dogs. METHODS The formulation was optimized based on the ternary phase diagram. The stability, particle size and Zeta potential of the formulation after emulsification in water were examined. The accumulated dissolution of the loratadine self-microemulsifying formulation in vitro was tested. The plasma concentrations were determined by LC-MS/MS and the pharmacokinetic behavior of the self-emulsifying formulation was evaluated by comparison with the commercial tablets. RESULTS The optimized self-emulsifying formulation was dispersed rapidly into water and the particle size of the formed emulsion was (28.15±1.65) nm. The dissolution of loratadine from the self-microemulsifying formulation at 15 min was more than 80%, much higher than that of the commercial product, which was less than 10%. The ρmax of the loratadine self-microemulsifying formulation was 9-fold of that of the marketed tablets, and the AUC0-t increased to 5.3 times of that of the tablets. CONCLUSION The self-microemulsifying drug delivery systems can increase loratadine dissolution in vitro and bioavailability in vivo significantly .
关键词
氯雷他定 /
自乳化 /
溶出 /
生物利用度
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Key words
loratadine /
self-emulsifying /
dissolution /
bioavailability
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中图分类号：
R969.1
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参考文献
[1] TANG J L, SUN J, HE Z G. Self-emulsifying drug delivery systems; Strategy for improving oral delivery of poorly soluble drugs .Curr Drug Ther, 2007, 2(1);85-93.[2] LIANG Y Q, XIAO J L, XU J. Comparison of the five kinds of second-generation antihistamines .Chin Pharmacist（中国药师）,2002,5（6）;368-369.[3] POPOVIC G, CAKAR M, DANICA A. Acid-base equilibria and solubility of loratadine and desloratadine in water and micellar media .J Pharm Biomed Anal, 2009,49（1）;42-47.[4] KHAN M Z, RAUSL D, MIKULCIC J H, et al. Classification of loratadine based on the biopharmaceutics drug classification concept and possible in vitro-in vivo correlation .Biol Pharm Bull, 2004,27(10);1630-1635.[5] PATIL P, PARADKAR A. Porous polystyrene beads as carriers for self-emulsifying system containing loratadine .AAPS Pharm Sci Tech, 2006, 7(1);1-7.[6] SZABADOS-NACSA A, AIGNER Z, SIPOS P, et al. Physico-chemical characterization and in vitro/in vivo evaluation of loratadine; Dimethyl-β-cyclodextrin inclusion complexes .J Pharm Biomed Anal, 2011, 55（2）;294-300.[7] POUTON C W, PORTER C J. Formulation of lipid-based delivery systems for oral administration; Materials, methods and strategies .Adv Drug Deliv Rev, 2008, 60(6); 625-637.[8] GURSOY R N, BENITA S. Self-emulsifying drug delivery systems (SEDDS) for improved oral delivery of lipophilic drugs . Biomed Pharmacother, 2004, 58（3）;173-182.[9] KOHLI K, CHOPRA S, DHAR D, et al. Self-emulsifying drug delivery systems; An approach to enhance oral bioavailability . Drug Discov Today, 2010, 15（21-22）;958-965. PERLMAN M E, MURDANDE S B, GUMKOWSKI M J, et al. Development of a self-emulsifying formulation that reduces the food effect for torcetrapib .Int J Pharm, 2008, 351（1-2）;15-22. LI R, LI M, GE W J. Comparison of dissolution of loratadine tablets or capsules in vitro from five manufacturters .J Pharm Practice(药学实践杂志), 2008, 26(5);350-352
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脚注
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基金
国家自然科学基金青年科学基金资助项目（81102390）
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