替尼泊苷冻干粉针剂的处方及冻干工艺研究

Study on the prescription and preparation technique of teniposide freeze dried powder injection

目的优化替尼泊苷冻干粉针剂的处方及冻干工艺。方法采用L9(34)正交试验优选处方,以原料药的浓度(A)、聚氧乙烯氢化蓖麻油的用量(B)、甘露醇的用量(C)、药液pH值(D)为考察因素,以制剂溶解性和含量为质量评价指标,确定最优处方组合A1B3C3D3;采用L9(34)正交试验确定冻干工艺,以预冻温度和时间(E)、升华干燥温度变化(F)、升华干燥时间和真空压力(G)、解析干燥温度和真空压力(H)为考察因素,以成品收率和残余水分为质量评价指标,确定最优冻干工艺组合E2F3G1H2。结果通过处方A1B3C3D3及冻干工艺E2F3G1H2制备3批替尼泊苷冻干粉针样品,3批样品的外观均为白色疏松块状,复溶性好,含量均在99.3%左右。结论该替尼泊苷冻干粉针处方及冻干工艺可行性好、重现性好。

Objective To optimize the prescription and freeze-dry technique of teniposide freeze dried powder injection. Methods The optimal prescription combination A1B3CP3 was determined by orthogonal experimental design L9（34） with the concentration of pharmaceutical product（A）, the dosage of poly-oxyethylene hydrogenated castor oil（B）, the dosage of mannitol（C） and physic liquor pH（D） as consideration factors. And the solubility and content of preparation were taken as quality evaluation index; The freeze-dried technique combination El3 G I H2 was determined by orthogonal experimental design L9（34） with the fore frozen temperature and time（E）, the sublimation drying temperature change（F）, the resolution drying time and vacuum pressure（G） and resolve drying temperature and drying temperature（H） as consideration factors. And the product yield and remnant water content were taken as quality evaluation index. Results Three batchs of teniposide for freeze dried powder injection were prepared with A1B3CP3 prescription and E2F3GIH2 freeze-dried technique and the appearance of the three batchs of samples were all white porosity block. The re-dissolvability was good. The content was about 99.3%. Conclusion The prescription and preparation technique ofteniposide for freeze dried powder injection is better feasibility and better reproducibility.