Novel micafungin sodium crystal forms and preparation method thereof

Abstract

The invention provides novel micafungin sodium crystal forms I and II and a preparation method thereof. Crystal forms I and II can be obtained by crystallization of a volatile solvent or a crystallization system containing a very small amount of water. The process is simple, and the crystal forms are easy to dry and suitable for industrial production. The angle of repose of the prepared crystal form I is smaller than 30 degrees, fluidity is good, and the angle of repose of the crystal form II is smaller than 40 degrees, and fluidity meets the production requirement. The crystal forms I and IIremain unchanged for one month under the dry condition and at room temperature. Appearance and fluidity are not changed apparently after the crystal form I is exposed at room temperature for 3 days under conditions of 85% RH and 97% RH and the crystal form II is exposed at room temperature for 3 days under conditions of 85% RH. The crystal forms I and II can better resist deliquescence, decreasedfluidity, difficult transfer and the like due to humidity factors, can adapt to more loose manufacturing, storage and transportation conditions, and provides support for research of novel preparations.

Description

Technical field [0001] The invention belongs to the technical field of drug crystal formations, and specifically relates to new crystal forms I and II of micafungin sodium, and a method for preparing the new crystal forms I and II. Background technique [0002] Micafungin (Micafungin) is the second echinocandin drug used in clinic after caspofungin. It mainly inhibits the synthesis of 1,3-β-D-glucan, the main component of fungal cell walls. Destroy the synthesis of fungal cell walls, affect the osmotic pressure of cell morphology, and lead to cell lysis and death, thereby better reducing the harm to the human body, while being efficient and reducing side effects as much as possible, so they are better than traditional antifungal drugs safer. Micafungin is mainly used to treat deep fungal infections such as Candida and Aspergillus, especially for the treatment of fungal infections in patients with low immunity such as chemotherapy and AIDS. [0003] Micafungin Sodium (also known a...

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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