Preparation method of amorphous atorvastatin calcium
An atorvastatin calcium and amorphous technology, which is applied in the field of preparation of amorphous atorvastatin calcium, can solve the problems of high toxicity of acetonitrile and difficulty in meeting the requirements of residual solvents, etc., and achieve the effect of high yield and simple process
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Embodiment 1
[0031] Put 20.0Kg of crystalline atorvastatin calcium into a 500L stainless steel still 1 with stirring and distillation tower 3 (diameter Φ300, equipped with 4m BX wire mesh packing), add 300L of methanol saturated with n-hexane in advance, stir and heat up Bring to a boil to completely dissolve the crystals of atorvastatin calcium. Open the alkane high tank 2 valve, add n-hexane dropwise, and control the drop rate at about 100L / hr. The azeotrope of alkane and methanol evaporated from the top of the distillation tower is condensed in the condenser 4, and the heating is adjusted so that the amount of the methanol phase in the condensate is about 100L / hr, and the stratification is carried out in the stratifier 5, and the methanol is continuously separated phase is placed in the methanol phase storage tank 6, and the upper n-hexane phase is all refluxed to the top of the distillation tower. After about 3 hours, when the temperature in the kettle rose to the boiling point of n-h...
Embodiment 2
[0034] In the device identical with embodiment 1, drop into 20.0Kg crystalline atorvastatin calcium, add about 300L of the methanol phase that separates when last batch of distillation, stir and be warmed up to boiling, make atorvastatin calcium crystal dissolve completely. Open the dripping valve, drip the mixed solution formed by about 250L of the filtrate in Example 1 and the added 50L n-hexane, the rate of addition is controlled at about 100L / hr, and carry out azeotropic distillation, cooling, and filtration the same as in Example 1 , dry operation, obtain amorphous atorvastatin calcium 19.9Kg.
Embodiment 3
[0036] In the same device as in Example 1, 20.0Kg of crystalline atorvastatin calcium was dropped into, and 300L of methanol saturated with cyclohexane was added in advance, and when the temperature in the still was controlled to reach about 80°C, heating and dripping were stopped, and the mixture was stirred under stirring. The material was cooled to 15° C., and other operations were the same as in Example 1, and finally 19.7 Kg of amorphous atorvastatin calcium was obtained.
[0037] The X-ray diffraction pattern of the amorphous atorvastatin calcium prepared according to this embodiment is shown in Figure 3, it can be seen that the atorvastatin calcium has reached the amorphous state.
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