New micafungin sodium crystal form II and preparation method thereof

Abstract

The invention provides novel micafungin sodium crystal forms I and II and a preparation method thereof. The crystal form I and the crystal form II can be obtained through crystallization of a volatile solvent or a crystallization system containing a small amount of water, the process is simple, drying is easy, and the method is suitable for industrial production. The repose angle of the prepared crystal form I is less than 30 degrees, the fluidity is good, the repose angle of the crystal form II is less than 40 degrees, and the fluidity meets the production requirements. The crystal form I and the crystal form II are not changed after being placed for one month under a room-temperature dry condition. Under the conditions that the crystal form I is 85% RH and 97% RH and the crystal form II is 85% RH, the crystal form I and the crystal form II are placed at room temperature in an open manner for 3 days, and the appearance and fluidity change is not obvious. The crystal form I and the crystal form II can better resist the problems of deliquescence, liquidity reduction, difficult transfer and the like possibly caused by humidity factors, can adapt to looser manufacturing, storage and transportation conditions, and provide support for research of new preparations.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical crystal forms, and in particular relates to new crystal forms I and II of micafungin sodium and a preparation method for the new crystal forms I and II. Background technique [0002] Micafungin is the second echinocandin drug used clinically after caspofungin. It mainly inhibits the synthesis of 1,3-β-D-glucan, the main component of the fungal cell wall, thereby Destroying the synthesis of fungal cell walls, affecting the osmotic pressure of cell morphology, leading to cell lysis and death, thus better reducing the damage to the human body, and reducing side effects as much as possible while being highly effective, so they are more effective than traditional antifungal drugs during use safer. Micafungin is mainly used for the treatment of deep fungal infections such as Candida and Aspergillus, especially for the treatment of fungal infections in immunocompromised patients such as chemother...

AI Technical Summary

Problems solved by technology

Therefore, crystal forms B and C are unstable to humidity, the preparation process needs to control the moisture content, and can only be obtained by conversion of crystal form A, which is not suitable for large-scale production

In addition, both crystal forms A and B are columnar slender crystals with poor fluidity and inconvenient handling in the production process.

[0008] In summary, there is currently a lack of a crystal form of micafungin sodium that has a simple preparation process, is suitable for large-scale industrial production, has less solvent residue, stable properties, and is convenient for production and storage.

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