Novel crystal form D of Retigabine and preparation method thereof

Abstract

The invention relates to the field of medicinal chemistry, in particular to a novel crystal form D of N-(2- amino-4-(4- fluoro benzyl amino) phenyl) ethyl carbamate (Retigabine) and a preparation method of the novel crystal form D. The invention provides X-ray powder diffraction characteristic absorption peaks and DSC (differential scanning calorimetry) endothermic transition peaks of the novel crystal form. The novel crystal form D of the Retigabine is characterized in that the crystal has characteristic absorption peaks at angles of (2 theta) 5.18 DEG, 10.60 DEG, 13.22 DEG, 13.98 DEG, 15.70DEG, 18.26 DEG, 20.46 DEG, 21.40 DEG, 22.22 DEG, 22.58 DEG, 23.06 DEG, 24.44 DEG, 24.82 DEG, 27.38 DEG and 28.28 DEG under the X-ray powder diffraction and the DSC endothermic transition of the novelcrystal form is at a temperature of 60-70 DEG C. The novel crystal form D of the Retigabine is thin in grain size (the average grain size is 20-35 mum and normal distributed), and can be used for medicinal preparation production with no need for physical smashing, therefore, the production link is decreased, the production cost is reduced, the pollution and the medicinal property changing caused in smash process are avoided and the clinical medication safety is increased.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, and in particular relates to a new crystal form D of ethyl N-(2-amino-4-(4-fluorobenzylamino)phenyl)carbamate (retigabine) and a preparation method thereof . Background technique [0002] Retigabine (INN: Retigabine, USAN: Ezogabine), its chemical name is N-(2-amino-4-(4-fluorobenzylamino)phenyl) ethyl carbamate, and its molecular formula is C 16 h 18 FN 3 o 2 , the molecular weight is 303.3, and the chemical structural formula is as follows: [0003] [0004] Retigabine has anticonvulsant, antipyretic and analgesic activities and is therefore suitable for use in pharmaceutical compositions. At present, medicines using the compound as an active ingredient have been listed in the European Union and the United States. [0005] Patent DE4200259 discloses the preparation method of retigabine; patent CN1243506 describes three crystal forms of retigabine, respectively named variants A, B an...

AI Technical Summary

Problems solved by technology

A series of deficiencies such as non-specific crystal form, heterogeneous particle size, uncertain or low bioavailability, and difficult quality control have brought great obstacles to pharmaceutical preparations, especially in large-dose preparations. A series of inhomogeneities such as particle size and solubility bring high costs and risks to the quality control of drugs, and there are also high risks in clinical applications

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