CN106977466A - A kind of crystallization preparation method of high heap density Glipizide - Google Patents
A kind of crystallization preparation method of high heap density Glipizide Download PDFInfo
- Publication number
- CN106977466A CN106977466A CN201710168249.7A CN201710168249A CN106977466A CN 106977466 A CN106977466 A CN 106977466A CN 201710168249 A CN201710168249 A CN 201710168249A CN 106977466 A CN106977466 A CN 106977466A
- Authority
- CN
- China
- Prior art keywords
- glipizide
- heap density
- preparation
- solvent
- added
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
A kind of crystallization preparation method of high heap density Glipizide the invention provides heap density not less than 0.20g/ml, the good product mobility that the method is prepared, purity is up to more than 99.65%, the one way molar yield of crystallization process is more than 85%, it is to avoid the problem of loading amount is uneven in later stage production process.This method is simple to operation, and process yield is high, and production cost is low, and industry amplification conversion is simple, suitable for extensive commercial application.
Description
Technical field
The invention belongs to pharmaceutical technology field, more particularly to a kind of crystallization preparation method of high heap density Glipizide.
Background technology
Glipizide, CAS：29094-61-9, is the crystalline powder of white or off-white color, in ethanol soluble,very slightly,
It is almost insoluble in water, it is readily soluble in sig water.Its chemical structural formula is as follows：
Glipizide is sulfonyl urea antidiabetic medicine, earliest by Pharmacia companies（Purchased by Pfizer within 2002）Exploitation,
First in Italy's listing, clinic was applied to by U.S. FDA approval in 1984 within 1973.Glipizide is to diabetes patient
Person has therapeutic action, by stimulating islet β cell insulin, effect of the enhancing insulin to target tissue；It can also suppress
Pancreas islet only cells secrete glucagon, suppression glycogenolysis, promote muscle to utilize and consumption of glucose, can effectively reduce trouble
Person's empty stomach and postprandial blood sugar concentration.At present, the common pharmaceutical dosage form of Glipizide is tablet, capsule, controlled release tablet etc..
Although Glipizide is early at home production, because the concern to its heap density is less, cause commercially available lattice row pyrrole
The heap density of piperazine bulk drug is smaller（0.08g/ml~0.12g/ml）.This can not only make to produce between Glipizide bulk drug particle compared with
Strong electrostatic adsorption causes its mobility to be deteriorated, and can cause Glipizide in production process because content uniformity causes
Quality it is inconsistent the problem of.About being primarily upon its purity, crystal formation etc. in the preparation method of Glipizide in disclosed report
Index, although achieve certain effect at above-mentioned aspect, but still do not solve the problem of Glipizide bulk drug heap density is too small.It is high
The Glipizide of heap density can not only ensure that the loading amount in different dosage forms preparation process is homogeneous, and its packaging volume is compared with urine
In storage transport.Therefore, find a kind of high heap density and the Glipizide crystal preparation method with good flow performance seems
It is particularly important.
The content of the invention
It is an object of the invention to provide a kind of crystallization preparation method of high heap density Glipizide.
The technical scheme is that a kind of crystallization preparation method of high heap density Glipizide, it is characterised in that：
Glipizide is added in alcohols solvent, the solid-to-liquid ratio of Glipizide and alcohols solvent used is the g/ of 0.05 g/g~0.3
G, the stirring and dissolving at 60~80 DEG C was continuously stirred after 30~120 minutes, was cooled to 10~20 DEG C, and rate of temperature fall is 1~5 DEG C/
Min, 1~3h of constant temperature stirring afterwards；Then esters solvent is added, continues constant temperature and stirs 1~3h；Then filtered, with washing
Solvent washs filter cake, and is dried, and just can obtain the Glipizide of high heap density, described high heap density refers to heap density not
Less than 0.20g/ml.
According to the present invention, the one kind of described alcohols solvent in methanol, ethanol, isopropanol, n-butanol.
According to the present invention, the one kind of described esters solvent in ethyl acetate, butyl acetate, the addition of esters solvent
Measure as 2~5 times of reaction alcohols solvent weight used, stream rate of acceleration preferably 2~6g/min of esters solvent.
According to the present invention, the one kind of described cleaning solvent in methanol, ethanol, isopropanol, n-butanol, selection washing
During solvent, it is consistent with reaction alcohols solvent used.
, according to the invention it is preferred to, the product after filtration washing is dried under 40~50 DEG C, normal pressure.
It is not less than the beneficial effects of the invention are as follows the Glipizide heap density that the preparation method using the present invention is obtained
0.20g/ml, good product mobility, purity is up to more than 99.65%, and the one way molar yield of crystallization process is more than 85%, it is to avoid
The problem of loading amount is uneven in later stage production process.This method is simple to operation, and process yield is high, and production cost is low, industry amplification
Conversion is simple, suitable for extensive commercial application.
Embodiment：
Content, is described further with reference to specific embodiment for a better understanding of the present invention, but the present invention is not only limited to
This.
Embodiment 1
5g Glipizides are added in the container for filling 100g n-butanol solvents, the stirring and dissolving at 80 DEG C continuously stirs 30 points
Zhong Hou, is cooled to 10 DEG C, rate of temperature fall is 1 DEG C/min, the 3h of constant temperature stirring afterwards；200g ethyl acetate is added into container,
Stream rate of acceleration is 4g/min, is finished, constant temperature stirring 1h；Then filtered, filter cake is washed with n-butanol, normal pressure is done at 50 DEG C
Dry 14h.Final products molar yield is that 91.2%, HPLC purity is 99.65%, and heap density is 0.23g/ml.
Embodiment 2
16g Glipizides are added in the container for filling 100g methanol solvates, the stirring and dissolving at 60 DEG C is continuously stirred 60 minutes
Afterwards, 10 DEG C are cooled to, rate of temperature fall is 2 DEG C/min, the 3h of constant temperature stirring afterwards；300g butyl acetate, stream are added into container
Rate of acceleration is 6g/min, is finished, constant temperature stirring 3h；Then filtered, filter cake is washed with methanol, the constant pressure and dry at 40 DEG C
7h.Final products molar yield is that 93.7%, HPLC purity is 99.72%, and heap density is 0.20g/ml.
Embodiment 3
30g Glipizides are added in the container for filling 100g alcohol solvents, the stirring and dissolving at 70 DEG C continuously stirs 120 points
Zhong Hou, is cooled to 15 DEG C, rate of temperature fall is 5 DEG C/min, the 1h of constant temperature stirring afterwards；500g ethyl acetate is added into container,
Stream rate of acceleration is 2g/min, is finished, constant temperature stirring 2h；Then filtered, filter cake is washed with ethanol, the constant pressure and dry at 45 DEG C
10h.Final products molar yield is that 94.9%, HPLC purity is 99.85%, and heap density is 0.24g/ml.
Embodiment 4
25g Glipizides are added in the container for filling 100g isopropanol solvents, the stirring and dissolving at 75 DEG C continuously stirs 90 points
Zhong Hou, is cooled to 20 DEG C, rate of temperature fall is 5 DEG C/min, the 2h of constant temperature stirring afterwards；300g butyl acetate is added into container,
Stream rate of acceleration is 3g/min, is finished, constant temperature stirring 1h；Then filtered, filter cake is washed with isopropanol, normal pressure is done at 50 DEG C
Dry 12h.Final products molar yield is that 93.3%, HPLC purity is 99.78%, and heap density is 0.23g/ml.
Embodiment 5
15g Glipizides are added in the container for filling 100g isopropanol solvents, the stirring and dissolving at 70 DEG C continuously stirs 60 points
Zhong Hou, is cooled to 15 DEG C, rate of temperature fall is 5 DEG C/min, the 3h of constant temperature stirring afterwards；200g butyl acetate is added into container,
Stream rate of acceleration is 5g/min, is finished, constant temperature stirring 3h；Then filtered, filter cake is washed with isopropanol, normal pressure is done at 50 DEG C
Dry 12h.Final products molar yield is that 94.2%, HPLC purity is 99.65%, and heap density is 0.22g/ml.
Embodiment 6
10g Glipizides are added in the container for filling 100g methanol solvates, the stirring and dissolving at 55 DEG C is continuously stirred 40 minutes
Afterwards, 10 DEG C are cooled to, rate of temperature fall is 3 DEG C/min, the 2h of constant temperature stirring afterwards；250g ethyl acetate, stream are added into container
Rate of acceleration is 4g/min, is finished, constant temperature stirring 3h；Then filtered, filter cake is washed with ethanol, the constant pressure and dry at 40 DEG C
10h.Final products molar yield is that 91.5%, HPLC purity is 99.88%, and heap density is 0.25g/ml.
Claims (3)
1. a kind of crystallization preparation method of high heap density Glipizide, it is characterised in that comprise the following steps：
Glipizide is added in alcohols solvent, the solid-to-liquid ratio of Glipizide and alcohols solvent used is 0.05 ~ 0.3 g/g, in
Stirring and dissolving at 60 ~ 80 DEG C, is continuously stirred after 30 ~ 120min, is cooled to 10 ~ 20 DEG C, and rate of temperature fall is 1 ~ 5 DEG C/min, 10 ~
20 DEG C of constant temperature stir 1~3h；Then esters solvent is added, continues constant temperature and stirs 1 ~ 3h；Filtering, filter cake is washed with cleaning solvent,
Dry, obtain the Glipizide of high heap density, described high heap density refers to that heap density is not less than 0.20g/ml.
2. preparation method according to claim 1, it is characterised in that described alcohols solvent is selected from methanol, ethanol, isopropyl
One kind in alcohol, n-butanol.
3. preparation method according to claim 1, it is characterised in that esters solvent is in ethyl acetate, butyl acetate
One kind.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710168249.7A CN106977466B (en) | 2017-03-21 | 2017-03-21 | A kind of crystallization preparation method of high heap density Glipizide |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710168249.7A CN106977466B (en) | 2017-03-21 | 2017-03-21 | A kind of crystallization preparation method of high heap density Glipizide |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN106977466A true CN106977466A (en) | 2017-07-25 |
| CN106977466B CN106977466B (en) | 2018-07-31 |
Family
ID=59339568
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710168249.7A Active CN106977466B (en) | 2017-03-21 | 2017-03-21 | A kind of crystallization preparation method of high heap density Glipizide |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106977466B (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102993106A (en) * | 2012-12-24 | 2013-03-27 | 武汉武药制药有限公司 | Novel synthesis route of glipizide |
| 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 |
| CN106187921A (en) * | 2016-07-09 | 2016-12-07 | 威海迪素制药有限公司 | A kind of preparation method of glipizide crystallization |
-
2017
- 2017-03-21 CN CN201710168249.7A patent/CN106977466B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102993106A (en) * | 2012-12-24 | 2013-03-27 | 武汉武药制药有限公司 | Novel synthesis route of glipizide |
| 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 |
| CN106187921A (en) * | 2016-07-09 | 2016-12-07 | 威海迪素制药有限公司 | A kind of preparation method of glipizide crystallization |
Non-Patent Citations (2)
| Title |
|---|
| KUMAR DINESH，等: "Spherical crystallization of glipizide for improvement of micrometric properties", 《INTERNATIONAL JOURNAL OF PHARMACY AND LIFE SCIENCES》 * |
| 刘炳朋，等: "格列吡嗪的合成", 《中国医药工业杂志》 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN106977466B (en) | 2018-07-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101439022B (en) | Method for preparing clindamycin phosphate powder injection raw medicine | |
| CN106397249A (en) | High-stability LCZ696 crystallized powder and a preparing method thereof | |
| WO2021227146A1 (en) | N-[8-(2-hydroxybenzoyl)amino]monopotassium octanoate crystal compound, and preparation method therefor and use thereof | |
| CN106977466B (en) | A kind of crystallization preparation method of high heap density Glipizide | |
| CN102285970B (en) | Esomeprazole compound, preparation method and pharmaceutical compoistion | |
| CN106187921B (en) | A kind of preparation method of Glipizide crystallization | |
| CN103735544B (en) | A kind of preparation technology of vildagliptin/metformin hydrochloride compound preparation | |
| CN103565806A (en) | Roflumilast oral preparation and preparation method thereof | |
| CN103214382B (en) | Meclofenoxate hydrochloride compound and pharmaceutical composition thereof | |
| CN101647781B (en) | Preparation method of ligustrazine phosphate powder injection | |
| CN106397409B (en) | A kind of preparation method of candesartan Cilexetil crystal form I spheroidal crystal | |
| CN103159737B (en) | Esomeprazole sodium compound and medicine composition | |
| CN103044509B (en) | Gamma-cytidine-5'-disodium triphosphate crystal compound, and preparation method and drug composition of crystal compound | |
| CN102516338B (en) | Capecitabine compound, pharmaceutical composition and preparation method thereof | |
| CN104151324B (en) | A kind of solvent crystallization prepares the method for ampicillin | |
| CN103724266B (en) | Remove first Ivabradine salt and its preparation method and application | |
| CN109646409A (en) | A kind of amoxicillin granules and preparation method thereof | |
| CN111057038A (en) | Novel crystal form of stiripentol | |
| CN113116837B (en) | Pioglitazone hydrochloride sustained-release tablet and preparation method thereof | |
| CN107814815A (en) | A kind of bromocriptine methanesulfonate novel crystal forms | |
| CN103565753A (en) | Ambroxol hydrochloride grain and preparation method thereof | |
| CN115212171B (en) | Ticagrelor sustained-release pellet and pharmaceutical preparation containing same | |
| CN105106129A (en) | Pharmaceutical lansoprazole composite granules for treating digestive system diseases | |
| CN106432021A (en) | Preparation method of fudosteine crystals | |
| CN102532122A (en) | Method for preparing rosiglitazone tartrate |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20191023 Address after: 264205 Guangzhou East Road South and an East Road East, Wendeng economic and Technological Development Zone, Weihai City, Shandong Province Co-patentee after: WEIHAI DISU PHARMACEUTICAL Co.,Ltd. Patentee after: Dijia Pharmaceutical Group Co.,Ltd. Co-patentee after: DISHA PHARMACEUTICAL GROUP Co.,Ltd. Address before: Tianrun road Wendeng Economic Development Zone in Weihai City, Shandong Province, No. 268 264205 Co-patentee before: DISHA PHARMACEUTICAL GROUP Co.,Ltd. Patentee before: WEIHAI DISU PHARMACEUTICAL Co.,Ltd. |
|
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20210722 Address after: 264205 Wendeng economic and Technological Development Zone, Weihai City, Shandong Province Patentee after: Dijia Pharmaceutical Group Co.,Ltd. Patentee after: DISHA PHARMACEUTICAL GROUP Co.,Ltd. Address before: 264205 Wendeng economic and Technological Development Zone, Weihai City, Shandong Province Patentee before: Dijia Pharmaceutical Group Co.,Ltd. Patentee before: WEIHAI DISU PHARMACEUTICAL Co.,Ltd. Patentee before: DISHA PHARMACEUTICAL GROUP Co.,Ltd. Effective date of registration: 20210722 Address after: 264205 268 Tianrun Road, Wendeng economic and Technological Development Zone, Weihai, Shandong Patentee after: Dijia Pharmaceutical Group Co.,Ltd. Address before: 264205 Wendeng economic and Technological Development Zone, Weihai City, Shandong Province Patentee before: Dijia Pharmaceutical Group Co.,Ltd. Patentee before: DISHA PHARMACEUTICAL GROUP Co.,Ltd. |
|
| CP03 | Change of name, title or address | ||
| CP03 | Change of name, title or address |
Address after: No. 268, Tianrun Road, Wendeng Economic and Technological Development Zone, Weihai City, Shandong Province, 264200 Patentee after: Dijia Pharmaceutical Group Co.,Ltd. Address before: 264205 268 Tianrun Road, Wendeng economic and Technological Development Zone, Weihai, Shandong Patentee before: Dijia Pharmaceutical Group Co.,Ltd. |