氯雷他定自微乳制剂的体内外评价

 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ρ_max是片剂的9倍，并且AUC_0-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。

Assessment of A Self-Microemulsifying Formulation of Loratadine in Vitro and in Vivo

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 ρ_max of the loratadine self-microemulsifying formulation was 9-fold of that of the marketed tablets, and the AUC_0-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 .