Preparation method of pharmaceutical terbutaline sulfate crystal form B

Abstract

The invention discloses a preparation method of a pharmaceutical terbutaline sulfate crystal form B. The preparation method comprises the following steps: S1, dissolving terbutaline sulfate of an amorphous form B in pure water, and conducting stirring and dissolving to obtain a terbutaline sulfate aqueous solution; S2, dropwise adding the amorphous form B terbutaline sulfate aqueous solution obtained in the step S1 into an alcohol or ketone solvent, conducting stirring for dissolving, adding a crystal seed of the terbutaline sulfate crystal form B, and conducting stirring for crystallizing toobtain a terbutaline sulfate crystal solution of the crystal form B; and S3, filtering the terbutaline sulfate crystal liquid with the crystal form B obtained in the step S2 and conducting drying to obtain a terbutaline sulfate crystal form B, wherein the ratio of the mass (unit: g) of the amorphous form B terbutaline sulfate to the mass (unit: g) of pure water to the mass (unit: g) of the crystalseed of the terbutaline crystal form B to the volume (unit: mL) of the alcohol or ketone solvent is 1:(4-5):(0.01-0.1):(50-60). The method has the advantages of simple operation, high repeatability,environment-friendly raw materials, and easy realization of industrial production application.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to a preparation method of terbutaline sulfate crystal form B suitable for medicine. Background technique [0002] α-[(tert-butylamino)methyl]-3,5-dihydroxybenzyl alcohol sulfate (2:1), ie Terbutaline Sulfate, CAS#[23031-32-5], molecular formula for (C 12 h 19 NO 3 ) 2 .H 2 SO 4 , its chemical structure is as follows: [0003] [0004] Terbutaline sulfate, also known as albuterol and terbutaline, was developed by AstraZeneca Pharmaceuticals Co., Ltd. and was produced and marketed abroad in 1988. Terbutaline sulfate is an adrenergic agonist, which can selectively excite β2-receptors to relax bronchial smooth muscle, inhibit the release of endogenous spasm-causing substances and edema caused by endogenous mediators, and improve bronchial mucosal ciliary epithelial Clearance ability, but also relaxation of uterine smooth muscle. Clinically, it is mainly used for the treatm...

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Problems solved by technology

Patent CN201310560213.5, Patent CN201510758230.9, Patent CN201510758230.9, Synthesis of Terbutaline Sulfate in Literature [J] Chinese Journal of Pharmaceutical Industry, 1999, 30(1): 1-4, Synthesis Process of Terbutaline in Literature Improvement, [J] Journal of Shenzhen University Science and Technology Edition, 2005, 22 (2): 105-108 and other disclosed preparation methods, the product crystal forms obtained are mostly crystal forms such as monohydrate and polyhydrate of terbutaline sulfate, Not a stable form B, unable to meet pharmaceutical standards

[0008] Patent CN101475497A discloses a method for preparing terbutaline sulfate crystal form B by using a mixed solvent, which uses a water-saturated ester solvent A or a water-saturated ester solvent A mixed with one or more organic solvents B , the terbutaline sulfate product of amorphous form B is converted into the terbutaline sulfate product of crystal form B; wherein the mixed solution used is complicated to operate, and the mixing ratio is difficult to control, and the obtained terbutaline sulfate product may be A mixture of multiple crystal forms, and the type of solvent used may cause the risk of solvent residues not meeting the pharmaceutical standards. The operation of obtaining terbutaline sulfate crystal form B by volatilizing the organic solvent under normal pressure or drying under nitrogen flow at 50°C is not necessary. Easy for industrial production and application

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