A kind of method for preparing glimepiride crystal form I

Abstract

The invention relates to a preparation method of glimepiride crystal form I, which belongs to the technical field of preparation of raw materials. The preparation method of the Limepiride crystal form I of the present invention comprises the following steps: dissolving the crude glimepiride in an aqueous alcohol solution, adding an appropriate amount of ammonia water, stirring to dissolve; filtering, adding acetic acid to the filtrate, and neutralizing the filtrate Ammonia in the crystalline form II, to obtain glimepiride crystal form II; to the crystal form II, add a ketone solvent 4 to 8 times its mass, stir at a temperature range of 10 to 35 °C for more than 10 hours, filter, and bake at 70 °C dry to obtain the glimepiride crystal form I product. The invention obtains a high-quality glimepiride crystal form I bulk drug.

Description

technical field [0001] The invention relates to a preparation method of glimepiride crystal form I, which belongs to the technical field of preparation of raw materials. Background technique [0002] Glimepiride (compound of formula I), as a novel sulfonamide hypoglycemic drug, is used for the treatment of type 2 diabetes. Foreign studies have found that it has a strong extramembrane hypoglycemic effect, including increasing insulin sensitivity and simulating the action of peripheral insulin, improving the translocation / dephosphorylation of glucose transporter (GLUT-4), and increasing the concentration of glucose in peripheral tissues. ingest. Among all sulfonamides, glimepiride has the lowest ratio of plasma insulin rise to blood glucose fall. [0003] [0004] The common forms of glimepiride are: amorphous, crystal form I, crystal form II, domestic reports of α, β, γ, δ, ε and other crystal forms. Among them, crystal form I is a pharmaceutical crystal form, which is ...

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Problems solved by technology

[0009] Experiments have found that crystal form I is relatively easy to obtain, but it is very easy to cause solvent wrapping during the crystallization process. The solvent wrapped in this kind of wrapping is very stable. It can be dried by drying, increasing the drying time, vacuum drying, and drying after airflow crushing. cannot be removed or reduced to acceptable limits (ICH Q3C limit standard)

[0010] After experiments, the crystal form II can be transformed into the crystal form I under high temperature conditions above 140°C, but because the crystal transformation temperature is too high, glimepiride is easy to degrade, deteriorate and change color, and its main degradation impurities are the following formula (compound of formula 2), And exceed the standard (greater than 0.4%)

Therefore, this crystal conversion process has no practical value in the production of glimepiride API

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