CN106187921A - A kind of preparation method of glipizide crystallization - Google Patents
A kind of preparation method of glipizide crystallization Download PDFInfo
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- CN106187921A CN106187921A CN201610538814.XA CN201610538814A CN106187921A CN 106187921 A CN106187921 A CN 106187921A CN 201610538814 A CN201610538814 A CN 201610538814A CN 106187921 A CN106187921 A CN 106187921A
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- glipizide
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- ZJJXGWJIGJFDTL-UHFFFAOYSA-N glipizide Chemical compound C1=NC(C)=CN=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZJJXGWJIGJFDTL-UHFFFAOYSA-N 0.000 title claims abstract description 40
- 229960001381 glipizide Drugs 0.000 title claims abstract description 39
- 238000002360 preparation method Methods 0.000 title claims abstract description 18
- 238000002425 crystallisation Methods 0.000 title abstract description 10
- 230000008025 crystallization Effects 0.000 title abstract description 10
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims abstract description 34
- 239000000047 product Substances 0.000 claims abstract description 24
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 18
- 238000003756 stirring Methods 0.000 claims abstract description 16
- 239000013078 crystal Substances 0.000 claims abstract description 15
- 239000012046 mixed solvent Substances 0.000 claims abstract description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 10
- 239000000706 filtrate Substances 0.000 claims abstract description 9
- 239000012065 filter cake Substances 0.000 claims abstract description 8
- 239000002904 solvent Substances 0.000 claims abstract description 6
- 239000007788 liquid Substances 0.000 claims abstract description 4
- 239000000243 solution Substances 0.000 claims description 24
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 15
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 14
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 12
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 8
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 8
- 239000007864 aqueous solution Substances 0.000 claims description 7
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 7
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical group CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- 238000005406 washing Methods 0.000 claims description 5
- 239000002994 raw material Substances 0.000 claims description 2
- 239000002245 particle Substances 0.000 abstract description 6
- 238000009826 distribution Methods 0.000 abstract description 4
- 239000003814 drug Substances 0.000 abstract description 4
- 238000004140 cleaning Methods 0.000 abstract description 3
- 229940079593 drug Drugs 0.000 abstract description 3
- 238000000034 method Methods 0.000 description 8
- 238000001914 filtration Methods 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 238000011049 filling Methods 0.000 description 5
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 4
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 238000007670 refining Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000013270 controlled release Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 102000017011 Glycated Hemoglobin A Human genes 0.000 description 1
- 108010014663 Glycated Hemoglobin A Proteins 0.000 description 1
- 102000015779 HDL Lipoproteins Human genes 0.000 description 1
- 108010010234 HDL Lipoproteins Proteins 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 206010054949 Metaplasia Diseases 0.000 description 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 1
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
- 229940100389 Sulfonylurea Drugs 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 238000000498 ball milling Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 201000005577 familial hyperlipidemia Diseases 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000003914 insulin secretion Effects 0.000 description 1
- 239000010808 liquid waste Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000015689 metaplastic ossification Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D241/24—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Abstract
The invention belongs to crude drug preparing technical field, the preparation method crystallized particularly to a kind of glipizide.The technical scheme is that glipizide is added in isopropyl alcohol mixed solvent by the first step, solution solid-to-liquid ratio is 0.05 g/ml～0.1 g/ml, stirring and dissolving at 40～45 DEG C, continuous stirring 30～60 minutes.Second step addition sig water regulation pH value of solution, to 8～9, filters, decolouring；Filtrate being moved in crystallizer, addition hydrochloric acid solution regulation pH value of solution, to 6～7, adds crystal seed, growing the grain 1～2h, is then cooled to 5～10 DEG C, growing the grain 1～3h；Filter, wash filter cake with cleaning solvent, product is dried, obtain big granularity glipizide product.The invention provides a kind of big granularity glipizide crystallization preparation method, products obtained therefrom is not assembled, main granularity more than 10 microns, even particle size distribution.
Description
Technical field
The invention belongs to crude drug preparing technical field, the preparation method crystallized particularly to a kind of glipizide.
Background technology
Chemistry entitled 1-cyclohexyl-3-{4-[2-(5-methylpyrazine-2-the amide)-second of glipizide (Glipizide)
Base] benzene sulfonyl } urea, molecular formula is C21H27N5O4S, molecular weight is 445.54, and No. CAS is 29094-61-9, its chemical structural formula
It is shown below.
Glipizide is the one of second filial generation sulfonylurea orally-taken blood sugar reducing medicine, is primarily to facilitate islets of langerhansβEmiocytosis
Insulin, the insulin secretion especially promoting glucose to stimulate, there is reduction blood sugar concentration and the merit of glycosylated hemoglobin
Effect.Additionally, glipizide can be additionally used in improves hyperlipemia, reduce triglyceride and cholesterol levels, improve high density lipoprotein level
White cholesterol ratio in T-CHOL.Its common medicinal dosage form is tablet, capsule, controlled release tablet etc..Commercially available glipizide tablet is
2.5mg and 5mg specification.
Glipizide is developed by Pfizer Inc. the earliest, and lists its controlled release agent type product in 2010 in China.
Although glipizide early has production at home, but domestic glipizide crude drug outward appearance is powder (such as Fig. 1), matt, grain
Spend little, main granularity (D50) only 3 microns (such as Fig. 2), generally there is significant powder electrostatic adsorption phenomena, mobility of particle poor
Etc. problem, not only affect the production links such as its filtration drying, and seriously add the production pressure of its tablet processing.Lattice row pyrrole
The existence of piperazine the problems referred to above is largely because and does not use suitable refining crystallization process.Cause the reason of this phenomenon
It is that past people the most too much pay close attention to its building-up process (CN104177302B, CN104086490A) and formulation and technology
The optimization of (CN102133205B, CN104739795A) and regulation and control, pay close attention to or former based on secrecy the research of its crystallization processes is very few
Because seldom reporting.
Although the glipizide crystal formation preparation method of patent CN105399692A report improves lattice row to a certain extent
The powder fluidity of pyrazine, but its preparation method is relatively complicated, relates to ball milling and the non-common refining crystallization means such as turning crystalline substance that suspend,
Its corresponding procedure parameter is wayward, material purity is required height, does not possess refined purification effect, be easily generated mixed crystal phenomenon,
It is unsuitable for large-scale industrial production.Patent CN102993106B uses triethylamine, DMF, water mixed solvent
Refined glipizide not only has the risk of dissolvent residual, and liquid waste processing is difficult, and solvent recovery cost is high, is not suitable for industry
Metaplasia is produced.
Summary of the invention
Goal of the invention: the preparation method that a kind of glipizide crystallizes is provided.
The present invention is to obtain a kind of glipizide product that powder flowing performance is good, Electrostatic Absorption is little, to its refining crystallization
Technique has carried out systematic study, finally gives a kind of main granularity (D50) at 10-20 micrometer range, and the glipizide being evenly distributed
Crystalline product, its powder flowing performance is good and Electrostatic Absorption is little.
Owing to glipizide is the preparation of small dimension, although test proves to increase granularity, powder electrostatic absorption can be improved existing
As problems such as, mobility of particle differences, but, granularity the most to a certain extent, is unfavorable for again the control of the formulation content uniformity.Test
Prove main granularity (D50) it is the control of 10-20 micron, the beneficially quality of the pharmaceutical preparations.
Technical scheme
The technical scheme is that: a kind of main granularity (D50) 10-20 micrometer range glipizide crystallize preparation method,
It is characterized in that:
Glipizide is added in isopropyl alcohol mixed solvent by the first step, and solution solid-to-liquid ratio is 0.05 g/ml～0.1 g/ml,
Stirring and dissolving at 40～45 DEG C, continuous stirring 30～60 minutes.
Described isopropyl alcohol mixed solvent be isopropyl alcohol and water, acetone, acetonitrile, n-butyl alcohol the mixing of one or more molten
Agent, wherein isopropanol volume fraction in mixed solvent is 5%～15%.
Second step addition sig water regulation pH value of solution, to 8～9, filters, decolouring；Filtrate is moved in crystallizer, add salt
Acid solution regulation pH value of solution, to 6～7, adds crystal seed, growing the grain 1～2h, is then cooled to 5～10 DEG C, growing the grain 1～3h；Then enter
Row filters, and washs filter cake with cleaning solvent, is dried by product, obtains big granularity glipizide product.
Described sig water be the molar concentration of sodium bicarbonate aqueous solution be 0.001mol/L～0.01mol/L.
Described concentration of hydrochloric acid solution molar concentration is 0.1mol/L～1mol/L.
Described addition amount of seed is raw material weight 5 ‰～1%.
Described cleaning solvent is ethanol or ethyl acetate.
Described drying condition is 40～50 DEG C of temperature, and vacuum is 0.06MPa～0.09MPa, and drying time 5～12 is little
Time.
Beneficial effect:
The invention provides a kind of main granularity (D50) at 10-20 micrometer range glipizide crystallization preparation method, its product HPLC
Content reaches more than 99.3%, and crystal is not assembled, and granularity is big, main granularity (D50) more than 10 microns, even particle size distribution, crystallization
The one way molar yield of process is more than 87%.The glipizide crystal that the present invention provides, its complete crystal form, granularity is big, and magma is easy
Being filtered, washed and dried, the labor intensity of technological operation is low.
Accompanying drawing explanation
The crystallogram (amplifying 40 times) of Fig. 1: glipizide original product；
Fig. 2: the particle size distribution figure of glipizide original product；
Fig. 3: the crystallogram (amplifying 40 times) of big granularity glipizide；
Fig. 4: the particle size distribution figure of big granularity glipizide.
Detailed description of the invention
Embodiment 1
5g glipizide is added in the container filling 100mL isopropanol and water mixed solvent (volume ratio is 5:95), at 40 DEG C
Lower stirring and dissolving, continuous stirring is after 30 minutes, and the sodium bicarbonate aqueous solution regulation pH value of solution adding 0.01mol/L is 8, filters,
Decolouring；Filtrate being moved in crystallizer, adding 1mol/L hydrochloric acid solution regulation pH value of solution is 7, addition 0.05g crystal seed, growing the grain 1h,
Then 10 DEG C it are cooled to, sucking filtration after growing the grain 3h, use washing with alcohol filter cake, dry under conditions of at 40 DEG C, vacuum is 0.09MPa
Dry 5h.Final products molar yield is 87.5%, and HPLC purity is 99.85%.The brilliant of products obtained therefrom is practised as bar-shaped (such as Fig. 3 institute
Show), main granularity (D50) it is 10.92 microns (as shown in Figure 4).
Embodiment 2
5g glipizide is added in the container filling 50mL isopropanol and acetone mixed solvent (volume ratio is 3:17), at 45 DEG C
Lower stirring and dissolving, continuous stirring is after 60 minutes, and the sodium bicarbonate aqueous solution regulation pH value of solution adding 0.001mol/L is 9, filters,
Decolouring；Filtrate being moved in crystallizer, adding 0.1mol/L hydrochloric acid solution regulation pH value of solution is 6, adds 0.03g crystal seed, growing the grain
2h, is then cooled to 5 DEG C, and sucking filtration after growing the grain 1h washs filter cake by ethyl acetate, and at 50 DEG C, vacuum is the bar of 0.06MPa
12h it is dried under part.Final products molar yield is 88.7%, and HPLC purity is 99.88%.The brilliant of products obtained therefrom is practised as bar-shaped, main
Granularity (D50) it is 12.35 microns.
Embodiment 3
10g glipizide is added in the container filling 50mL isopropanol and acetonitrile mixed solvent (volume ratio is 1:10), 43
Stirring and dissolving at DEG C, continuous stirring is after 40 minutes, and the sodium bicarbonate aqueous solution regulation pH value of solution adding 0.005mol/L is 8.5,
Filter, decolouring；Filtrate being moved in crystallizer, adding 0.3mol/L hydrochloric acid solution regulation pH value of solution is 6, adds 0.05g crystal seed,
Growing the grain 1.5h, is then cooled to 5 DEG C, and sucking filtration after growing the grain 2h washs filter cake by ethyl acetate, and at 50 DEG C, vacuum is
12h it is dried under conditions of 0.06MPa.Final products molar yield is 88.7%, and HPLC purity is 99.88%.The crystalline substance of products obtained therefrom
Practise as bar-shaped, main granularity (D50) it is 14.05 microns.
Embodiment 4
8g glipizide is added in the container filling 100mL isopropanol and n-butanol mixed solvent (volume ratio is 1:9), 40
Stirring and dissolving at DEG C, continuous stirring is after 30 minutes, and the sodium bicarbonate aqueous solution regulation pH value of solution adding 0.01mol/L is 8, mistake
Filter, decolouring；Filtrate being moved in crystallizer, adding 0.8mol/L hydrochloric acid solution regulation pH value of solution is 6.5, adds 0.06g crystal seed,
Growing the grain 2h, is then cooled to 7 DEG C, and sucking filtration after growing the grain 2h uses washing with alcohol filter cake, and at 45 DEG C, vacuum is the bar of 0.08MPa
8h it is dried under part.Final products molar yield is 88.6%, and HPLC purity is 99.91%.The brilliant of products obtained therefrom is practised as bar-shaped, main grain
Degree (D50) it is 10.46 microns.
Embodiment 5
5g glipizide is added in the container filling 100mL isopropanol and acetonitrile, water mixed solvent (volume ratio is 1:3:6),
Stirring and dissolving at 45 DEG C, continuous stirring is after 40 minutes, and the sodium bicarbonate aqueous solution regulation pH value of solution adding 0.001mol/L is
9, filter, decolouring；Filtrate being moved in crystallizer, adding 0.5mol/L hydrochloric acid solution regulation pH value of solution is 6.5, adds 0.04g
Crystal seed, growing the grain 1.5h, then it is cooled to 5 DEG C, sucking filtration after growing the grain 2.5h, washs filter cake by ethyl acetate, vacuum at 40 DEG C
For being dried 12h under conditions of 0.06MPa.Final products molar yield is 89.3%, and HPLC purity is 99.86%.Products obtained therefrom
Brilliant habit is bar-shaped, main granularity (D50) it is 19.92 microns.
Present invention disclosure and the big granularity glipizide crystallization preparation method proposed, those skilled in the art can be by using for reference
Present disclosure, the link such as suitable feed change, technological parameter realizes.The method of the present invention and product are by preferred embodiment
Being described, person skilled substantially can be to method described herein in without departing from present invention, spirit and scope
It is modified with product or suitably changes and combine, realizing the technology of the present invention.Special needs to be pointed out is, all similar
Replacing and change apparent to those skilled in the art, they are considered as being included in present invention spirit, scope
With in content.
Claims (6)
1. main granularity D50The preparation method crystallized for the glipizide of 10-20 micron, it is characterised in that
Glipizide is added in isopropyl alcohol mixed solvent by the first step, and solution solid-to-liquid ratio is 0.05 g/ml～0.1 g/ml,
Stirring and dissolving at 40～45 DEG C, continuous stirring 30～60 minutes；
Second step addition sig water regulation pH value of solution, to 8～9, filters, decolouring；Filtrate is moved in crystallizer, add hydrochloric acid molten
Liquid regulation pH value of solution, to 6～7, adds crystal seed, growing the grain 1～2h, is then cooled to 5～10 DEG C, growing the grain 1～3h；Filter, with washing
Solvent washing filter cake, is dried product, obtains big granularity glipizide product.
2. preparation method described in claim 1, it is characterised in that isopropyl alcohol mixed solvent described in the first step selected from isopropanol with
The mixed solvent of one or more in water, acetone, acetonitrile, n-butyl alcohol, wherein isopropanol volume fraction in mixed solvent
It is 5%～15%.
3. preparation method described in claim 1, it is characterised in that sig water described in second step be molar concentration be 0.001mol/L
～the sodium bicarbonate aqueous solution of 0.01mol/L.
4. preparation method described in claim 1, it is characterised in that the molar concentration of hydrochloric acid solution described in second step is 0.1mol/L
～1mol/L.
5. preparation method described in claim 1, it is characterised in that when second step adds crystal seed, the addition of crystal seed is raw material weight
The 5 ‰～1% of amount.
6. preparation method described in claim 1, it is characterised in that after second step filters, the solvent of washing and filtering product is ethanol
Or ethyl acetate.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610538814.XA CN106187921B (en) | 2016-07-09 | 2016-07-09 | A kind of preparation method of Glipizide crystallization |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610538814.XA CN106187921B (en) | 2016-07-09 | 2016-07-09 | A kind of preparation method of Glipizide crystallization |
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| CN106187921A true CN106187921A (en) | 2016-12-07 |
| CN106187921B CN106187921B (en) | 2018-06-15 |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105399692A (en) * | 2015-12-18 | 2016-03-16 | 四川大学 | Glipizide crystal form III, and preparation method thereof |
| CN106866552A (en) * | 2017-03-20 | 2017-06-20 | 威海迪素制药有限公司 | A kind of preparation method of high-purity Glipizide crystal formation I crystallizations |
| CN106977466A (en) * | 2017-03-21 | 2017-07-25 | 威海迪素制药有限公司 | A kind of crystallization preparation method of high heap density Glipizide |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040258757A1 (en) * | 2002-07-16 | 2004-12-23 | Elan Pharma International, Ltd. | Liquid dosage compositions of stable nanoparticulate active agents |
| US20050019412A1 (en) * | 1998-10-01 | 2005-01-27 | Elan Pharma International Limited | Novel glipizide compositions |
| CN104086490A (en) * | 2014-07-17 | 2014-10-08 | 徐小强 | Glipizide compound as well as pharmaceutical composition containing glipizide compound and preparation method of glipizide compound |
| CN105399692A (en) * | 2015-12-18 | 2016-03-16 | 四川大学 | Glipizide crystal form III, and preparation method thereof |
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2016
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| US20050019412A1 (en) * | 1998-10-01 | 2005-01-27 | Elan Pharma International Limited | Novel glipizide compositions |
| US20040258757A1 (en) * | 2002-07-16 | 2004-12-23 | Elan Pharma International, Ltd. | Liquid dosage compositions of stable nanoparticulate active agents |
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| CN105399692A (en) * | 2015-12-18 | 2016-03-16 | 四川大学 | Glipizide crystal form III, and preparation method thereof |
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| RENUKA ET AL.: "Characterization of solid state forms of glipizide", 《POWDER TECHNOLOGY》 * |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105399692A (en) * | 2015-12-18 | 2016-03-16 | 四川大学 | Glipizide crystal form III, and preparation method thereof |
| CN106866552A (en) * | 2017-03-20 | 2017-06-20 | 威海迪素制药有限公司 | A kind of preparation method of high-purity Glipizide crystal formation I crystallizations |
| CN106977466A (en) * | 2017-03-21 | 2017-07-25 | 威海迪素制药有限公司 | A kind of crystallization preparation method of high heap density Glipizide |
Also Published As
| Publication number | Publication date |
|---|---|
| CN106187921B (en) | 2018-06-15 |
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