Crystallization method for preparing high-purity monodisperse I crystal form atorvastatin calcium in single kettle

[0087] Get 40g of methanol-water solution with methanol content of 15wt%, drop into 0.04g of I crystal form atorvastatin calcium, keep the solution temperature at 20°C, and ultrasonicate for 30min under the condition of ultrasonic power of 300W until the crystal particles are completely dispersed. The suspension is fed to a crystallizer as a solution for eluting crystallization.

[0088] Take 3.5 g of atorvastatin calcium raw material powder, add 20 g of anhydrous methanol, stir and dissolve in a water bath ultrasonically, then centrifuge and press filter to make methanol feed liquid.

[0089] Adopt the way of double-strand feeding of each material, drop methanol feed liquid and anti-solvent pure water into the above solution at the same time; keep the methanol concentration of the solvent in the solution in the co-current elution process basically unchanged, then 113.3g of water is required; Set the dissolution time to 2h, then the flow rate of water is 0.944g / min. The tempe...

[0096] Get 40g of methanol-water solution with methanol content of 25wt%, drop 0.085g of I crystal form atorvastatin calcium, keep the solution temperature at 20°C, and ultrasonicate for 100min under the ultrasonic power condition of 360W until the crystal particles are completely dispersed. The suspension is fed to a crystallizer as a solution for eluting crystallization.

[0097] Take 3.5 g of atorvastatin calcium raw material powder, add 20 g of anhydrous methanol, stir and dissolve in a water bath ultrasonically, then centrifuge and press filter to make methanol feed liquid.

[0098] Adopt the mode of double-strand feeding of every kind of material, drop methanol feed liquid and anti-solvent pure water in the above-mentioned solution simultaneously; Keep the methanol concentration of the solvent in the solution in the co-current elution process to be basically constant, then need water 60g; If the dissolution time is 4h, the flow rate of water is 0.25g / min. The temperatur...

[0105] Get 40g of methanol-water solution with a methanol content of 30wt%, add 0.15g of I crystal form atorvastatin calcium, keep the solution temperature at 20°C, and ultrasonicate for 1h under the condition of ultrasonic power of 360W until the crystal particles are completely dispersed. The suspension is fed to a crystallizer as a solution for eluting crystallization.

[0106] Take 2.98g of atorvastatin calcium raw material powder, add 17g of anhydrous methanol, stir and dissolve in a water-bath ultrasonic, then centrifuge and press filter to make methanol feed liquid.

[0107] Adopt the method of double-strand feeding of each material, drop methanol feed liquid and anti-solvent pure water into the above solution at the same time; keep the methanol concentration of the solvent in the solution in the co-current elution process basically unchanged, then 39.67g of water is required; Set the dissolution time to 204.5min, then the flow rate of water is 0.194g / min. The temperat...