Method for preparing rifampicin I crystal form

Abstract

The invention discloses a method for preparing a rifampicin I crystal form. The method comprises the following steps: under the action of stirring, adding rifampicin I crystal form crude products of which the purity is not less than 90% into a solution, wherein the concentration of the solutions is that the rifampicin : solvent equals to 0.16 to 0.30 g / mL; adding water of which the volume is 1 to 6% of the volume of the solvent, and rising temperature to 75 to 85 DEG C to dissolve the rifampicin crude products; performing vacuum evaporation crystallization, evaporating a rifampicin solution, stopping evaporation after crystals are separated out, growing the crystals for 20 to 40 minutes, then continuing evaporation, and when the volume of the distillate liquid is 20 to 60% of the volume of the solvent, stopping evaporation; performing cooling crystallization, reducing the temperature to 20 to 35 DEG C, and growing the crystals for 20 to 40 minutes; filtering magma to obtain products. The purity of the crystals is greater than 97%, the average granularity is larger than 170 microns, the bulk density is larger than 0.65 g / mL, and the yield is above 80%. The method has the characteristics that operation time is short, seed crystals are not required to be added, product appearances are regular and mobility is good, and the method is suitable for industrial application.

Description

technical field [0001] The invention belongs to the technical field of chemical engineering crystallization, and in particular relates to a preparation method of rifampicin I crystal form. Background technique [0002] Rifampicin, English name: Rifampicin, 3-(4-Methylpiperazinyliminomethyl)rifamycin SV; chemical name 3-[[(4-methyl-1-piperazinyl)imino]methyl]-rifamycin. Aliases: Lifuping, Meperifamycin, Rimidine. Molecular formula: C 43 h 58 N 4 o 12 , molecular weight: 822.95, CAS number: 13292-46-1. Its chemical structural formula is as follows: [0003] [0004] Rifampicin is a reddish-brown or brownish-red crystalline powder. The dry powder can be stored stably for more than 5 years. It is easily soluble in chloroform and dimethyl sulfoxide, soluble in ethyl acetate, methanol, tetrahydrofuran, propanol and tetrachloride Carbon, slightly soluble in water, its aqueous solution loses its effectiveness after being stored at room temperature for 10 hours, but adding ...

AI Technical Summary

Problems solved by technology

The disadvantage of this method is that the raw material concentration is low, the crystallization yield is low, and the preparation process needs to add crystal seeds, which increases the operation steps, and the crystallization operation time is long, about 15 hours. Poor performance, product sticky and easy to coalesce

[0011] Electron micrographs of commercially available I crystal form rifampicin products are as follows: figure 1 As shown, the crystal particle size is small, about 50μm, and the bulk density is low, about 0.4g / mL. The product is easily broken, has high adhesion, and is difficult to filter and dry.

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