地拉罗司颗粒剂处方工艺优化

Optimization of formulation for deferasirox granules

目的通过体外溶出度测定,对地拉罗司颗粒剂的处方和工艺进行优化,得到与原研溶出相似的产品。方法评估可能对溶出产生影响的处方工艺参数,合理变动,用HPLC测定药物体外溶出度。结果通过f;相似因子法对溶出结果进行评价,优化后的处方为,内相:活性成分55.97%、微晶纤维素pH101:14.4%、PVP K302.25%、交联聚维酮2.0%、泊洛沙姆1880.375%,外相:微晶纤维素pH102:18.5%、交联聚维酮5.0%、微晶硅胶0.50%、硬脂酸镁1.0%。工艺为,称量泊洛沙姆、PVP K30,加总质量24%的水溶解,制成有粘合剂与表面活性剂的溶液;称量其他内部辅料,加入制粒机,干粉混合,混匀后,边加溶液边混合,制成软材,之后进行60 s搅拌制粒,过6350μm筛打散,烘箱干燥至LOD≤2.0%,1000 r·min^(-1)过1575μm筛,称量除硬脂酸镁以外的外相辅料和内相辅料一同加入料斗混匀,再加硬脂酸镁,混匀,取出。结论优化后的制剂与原研体外溶出度相似性明显提高,降低了后续临床生物等效性试验的风险。

Objective To optimize the formulation and process of deferasirox granules by in vitro dissolution determination,and obtain a product similar to the original dissolution.Methods The method evaluates the formulation process parameters that may have an effect on dissolution.Reasonable changes are made.The drug results are determined by HPLC.Results The dissolution results are evaluated by f;similarity factor method.The optimized formulation was:internal phase:55.97%of active ingredient,microcrystalline cellulose pH 10114.4%,PVP K302.25%,PVPP 2.0%,poloxamer 1880.375%,external phase:microcrystalline cellulose pH 10218.5%,PVPP 5.0%,microcrystalline silica gel 0.50%,magnesium stearate 1.0%.The process is to weigh poloxamer and PVP K30,dissolve 24%of the total mass of water to make a mixed solution of binder and surfactant;weigh other internal auxiliary materials,add to a granulator,and mix with dry powder.After mixing,mix while adding the mixing liquid to make a soft material,and then carry out 60 s stirring and granulation,sieving through a 6350μm sieve,drying in an oven until LOD≤2.0%,and sieving at 1000 r·min^(-1)through a 1575μm sieve.The excipients and the internal phase excipients are added to the hopper and mixed together,and then magnesium stearate is added,mixed and taken out.Conclusion The similarity between the optimized formulation and the original research in vitro dissolution is significantly improved,which reduces the risk of subsequent clinical bioequivalence tests.