【摘要】 目的:制备难溶性药物尼群地平的共研粉末,并对其进行体外溶出度及家兔体内相对生物利用度评价。方法:采用共研磨法制备尼群地平-微晶纤维素-泊洛沙姆共研粉末,测定药物的体外溶出度,并通过物理鉴别方法考察药物的存在状态。采用HPLC法测定6只健康家兔分别口服尼群地平共研粉末(A)、物理混合粉末(B)和市售普通片(C)后不同时间血浆中尼群地平的浓度,计算体内相对生物利用度。结果:共研粉末中尼群地平的溶出度显著提高,药物的粒径也明显减小,主要以微晶状态存在。家兔口服尼群地平共研粉末后,与参比制剂B和C相比,Tm ax变小,Cm ax和AUC明显变大,相对生物利用度分别为341.12%和353.01%。结论:共研磨技术显著的提高了尼群地平的溶出速率和口服相对生物利用度。更多还原

【Abstract】 Objective: To prepare nitrendipine co-grinding powder,and to evaluate its dissolution rate in vitro and relative oral bioavailability in vivo in rabbits.Methods: Nitrendipine co-grinding powder was prepared by co-grinding with microcrystalline cellulose and poloxamer 188,and then drug dissolution rate and drug state in carriers were evaluated by dissolution tests and physical identifications.After oral administration of a single dose of nitrendipine co-grinding powder(formulation A),physica1 mixture powder(reference formulation B) and commercial tablets(reference formulation C) to each of six healthy rabbits,the plasma concentrations of nitrendipine at various times were determined by HPLC,and relative oral bioavailability were calculated.Results: The dissolution rate of drug was remarkably increased,the particle size of drug crystal was obviously diminished and a majority of drug was microcrystalline in nitrendipine co-grinding powder.After oral administration of formulation A,the Tmax value was shorten and the Cmax and AUC0~t values were raised magnificently.The relative oral bioavailability was 341.12% and 353.01%,respectively,compared with formulation B and C.Conclusion: Co-grinding method can obviously enhance the dissolution rate and relative oral bioavailability of the water insoluble drug nitrendipine.更多还原