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Preparation method of glipizide crystals

A technology for glipizide and crystallization, which is applied in the field of preparation of glipizide crystallization, can solve problems such as unfavorable formulation content uniformity, and achieve the effects of complete crystal form, low labor intensity and uniform particle size distribution

Active Publication Date: 2016-12-07
迪嘉药业集团股份有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] Since glipizide is a small-scale preparation, experiments have shown that although increasing the particle size can improve the electrostatic adsorption of powders and poor particle fluidity, the particle size is too large to a certain extent, which is not conducive to the control of the content uniformity of the preparation.

Method used

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  • Preparation method of glipizide crystals
  • Preparation method of glipizide crystals
  • Preparation method of glipizide crystals

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] Add 5g of glipizide into a container containing 100mL of isopropanol and water mixed solvent (volume ratio: 5:95), stir and dissolve at 40°C, and after stirring continuously for 30 minutes, add 0.01mol / L of sodium bicarbonate Adjust the pH of the solution to 8 with an aqueous solution, filter, and decolorize; transfer the filtrate to a crystallizer, add 1mol / L hydrochloric acid solution to adjust the pH of the solution to 7, add 0.05g of seed crystals, grow crystals for 1 hour, then cool down to 10°C, and grow crystals for 3 hours Filter with suction, wash the filter cake with ethanol, and dry at 40° C. for 5 hours under a vacuum of 0.09 MPa. The molar yield of the final product was 87.5%, and the HPLC purity was 99.85%. The crystal habit of the resulting product is rod-like (such as image 3 shown), the primary particle size (D 50 ) to 10.92 µm (as Figure 4 shown).

Embodiment 2

[0029] Add 5g of glipizide into a container containing 50mL of isopropanol and acetone mixed solvent (volume ratio: 3:17), stir and dissolve at 45°C, and after continuous stirring for 60 minutes, add 0.001mol / L of sodium bicarbonate Adjust the pH of the solution to 9 with an aqueous solution, filter, and decolorize; transfer the filtrate to a crystallizer, add 0.1mol / L hydrochloric acid solution to adjust the pH of the solution to 6, add 0.03g of seed crystals, grow crystals for 2 hours, then cool down to 5°C, and grow crystals for 1 hour After suction filtration, the filter cake was washed with ethyl acetate, and dried at 50° C. for 12 hours under a vacuum of 0.06 MPa. The molar yield of the final product was 88.7%, and the HPLC purity was 99.88%. The crystal habit of the obtained product is rod-shaped, and the main particle size (D 50 ) is 12.35 µm.

Embodiment 3

[0031] Add 10g of glipizide into a container containing 50mL of a mixed solvent of isopropanol and acetonitrile (1:10 in volume ratio), stir and dissolve at 43°C, and after stirring continuously for 40 minutes, add 0.005mol / L of sodium bicarbonate Adjust the pH of the solution to 8.5 with an aqueous solution, filter, and decolorize; transfer the filtrate to a crystallizer, add 0.3mol / L hydrochloric acid solution to adjust the pH of the solution to 6, add 0.05g of seed crystals, and grow crystals for 1.5h, then cool down to 5°C and grow crystals After 2 hours, filter with suction, wash the filter cake with ethyl acetate, and dry at 50° C. for 12 hours under a vacuum of 0.06 MPa. The molar yield of the final product was 88.7%, and the HPLC purity was 99.88%. The crystal habit of the obtained product is rod-shaped, and the main particle size (D 50 ) is 14.05 µm.

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Abstract

The invention belongs to the technical field of bulk pharmaceutical chemical preparation and particularly relates to a preparation method of glipizide crystals. According to the technical scheme, the preparation method comprises the first step that glipizide is added into an isopropanol mixed solvent, the solid-to-liquid ratio of the solution is 0.05 g / ml to 0.1 g / ml, and stirring is conducted continuously for 30-60 minutes at the temperature of 40-45 DEG C for dissolution; the second step that dilute alkaline liquor is added, the pH of the solution is regulated to 8-9, and filtering and decoloring are conducted; the filtrate is transferred into a crystallizer, a hydrochloric acid solution is added, the pH of the solution is regulated to 6-7, seed crystals are added and cultured for 1-2 h, then the temperature is dropped to 5-10 DEG C, and the crystals are cultured for 1-3 h; filtering is conducted, a cleaning solvent is used for washing filter cakes, products are dried, and the high-granularity glipizide products are obtained. According to the preparation method of the high-granularity glipizide crystals, the obtained products do not aggregate, the main granularity is 10 microns or above, and granularity distribution is uniform.

Description

technical field [0001] The invention belongs to the technical field of preparation of crude drugs, in particular to a preparation method of glipizide crystals. Background technique [0002] The chemical name of Glipizide is 1-cyclohexyl-3-{4-[2-(5-methylpyrazine-2-amide)-ethyl]benzenesulfonyl}urea, and its molecular formula is C 21 h 27 N 5 o 4 S, the molecular weight is 445.54, the CAS number is 29094-61-9, and its chemical structure is shown in the following formula. [0003] [0004] Glipizide is a second-generation sulfonylurea oral hypoglycemic drug, mainly used to promote the β Cells secrete insulin, especially to promote glucose-stimulated insulin secretion, which has the effect of reducing blood sugar concentration and glycosylated hemoglobin. In addition, glipizide can also be used to improve hyperlipidemia, reduce triglyceride and cholesterol levels, and increase the ratio of high-density lipoprotein cholesterol to total cholesterol. Its common pharmaceuti...

Claims

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Application Information

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IPC IPC(8): C07D241/24
CPCC07B2200/13C07D241/24
Inventor 王冠姜凯王兆杰高永吉
Owner 迪嘉药业集团股份有限公司
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