CN103193614A - Preparation method for pharmaceutic adjuvant--magnesium stearate - Google Patents
Preparation method for pharmaceutic adjuvant--magnesium stearate Download PDFInfo
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- CN103193614A CN103193614A CN2013100363320A CN201310036332A CN103193614A CN 103193614 A CN103193614 A CN 103193614A CN 2013100363320 A CN2013100363320 A CN 2013100363320A CN 201310036332 A CN201310036332 A CN 201310036332A CN 103193614 A CN103193614 A CN 103193614A
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- magnesium stearate
- pharmaceutical excipient
- preparation
- stearic acid
- sodium hydroxide
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Abstract
The invention provides a preparation method for a pharmaceutic adjuvant--magnesium stearate. The preparation method comprises the following two steps: step 1, subjecting stearic acid and sodium hydroxide to a saponification reaction; and step 2, reacting sodium stearate produced by stearic acid and sodium hydroxide with magnesium sulfate so as to produce the magnesium stearate. The pharmaceutic adjuvant magnesium stearate produced by using the method provided by the invention has stable quality indexes, and in particular, the content of MgO accords with requirements prescribed in Chinese Pharmacopoeia (2010 edition); production process conditions are easily controllable, and the produced magnesium stearate has a good color.
Description
Technical field
The present invention relates to a kind of preparation method of pharmaceutical excipient Magnesium Stearate.
Background technology
Magnesium Stearate is the agent of a kind of character excellent lubrication, and its principal feature is that oilness is good, light weight, strong adhesion, can be widely used in industries such as medicine, foods and cosmetics.In pharmaceutical industries, Magnesium Stearate is mainly as the lubricant in the pharmaceutical tablet compressing tablet process.
As the pharmaceutical excipient Magnesium Stearate that uses in the pharmaceutical industries, higher to its specification of quality, wherein key index is that the content of MgO is 6.5%-7.5%(Chinese Pharmacopoeia 2010 editions).The product that exceeds this scope all can not use as pharmaceutical excipient.
The method of existing production pharmaceutical excipient Magnesium Stearate has multiple, exists technology complicated mostly, the uppity shortcoming of preparation condition, the product quality indicator less stable of the pharmaceutical excipient Magnesium Stearate of producing.
Summary of the invention
The technical problem to be solved in the present invention provides a kind of preparation method of pharmaceutical excipient Magnesium Stearate, utilize the quality index of the pharmaceutical excipient Magnesium Stearate that this method produces stable, particularly the content of MgO can meet 2010 editions requirements of Chinese Pharmacopoeia, and manufacturing condition is easy to control, and product color is good.
For solving the problems of the technologies described above, the invention provides a kind of preparation method of pharmaceutical excipient Magnesium Stearate, may further comprise the steps:
The first step: under whipped state, 0.14-0.16kg sodium hydroxide is dissolved in 3-4L deionized water, continue to stir 15-25min after being warming up to 60-75 ℃, make sodium hydroxide solution, be incubated 65-75 ℃ stand-by;
Second step: under whipped state with the MgSO of 0.4-0.6kg
47H
2O dissolves in 14-16L deionized water, continue to stir 20-40min after being warming up to 60-75 ℃, makes Adlerika, be incubated 65-75 ℃ stand-by;
The 3rd step: the 1kg stearic acid is joined in 15-25L deionized water, be heated to 85-95 ℃, stearic acid is dissolved fully be oily matter and float on liquid level; The sodium hydroxide solution that the first step is prepared slowly joins in the mixed solution of stearic acid and water under well-beaten condition, and reaction makes sodium stearate solution behind 2-3h, be cooled to 65-75 ℃ stand-by;
The 4th step: prepared Adlerika of second step is slowly joined under whipped state in the prepared sodium stearate solution of the 3rd step, keep stirring 50-90min under 65-75 ℃ of conditions of temperature, be cooled to normal temperature then, leave standstill in the rotary and centrifugal machine that changes the band filter cloth behind 8-10h over to and separate, get Magnesium Stearate crude product filter cake;
The 5th step: Magnesium Stearate crude product filter cake is washed, dewaters repeatedly, carry out drying meet the requirement of Chinese Pharmacopoeia 2010 editions to the water-soluble impurity index of Magnesium Stearate filter cake after, namely get the pharmaceutical excipient Magnesium Stearate.
For the purpose of the concise explanation problem, below the preparation method of pharmaceutical excipient Magnesium Stearate of the present invention is all abbreviated as present method.
Present method comprises two-step reaction.
The first step is the saponification reaction that stearic acid and sodium hydroxide carry out, and reaction equation is:
CH
3(CH
2)
16COOH+NaOH→CH
3(CH
2)
16COONa+H
2O
Second step was that sodium stearate and the sal epsom reaction that stearic acid and sodium hydroxide generate generates Magnesium Stearate, and reaction equation is:
2CH
3(CH
2)
16COONa+MgSO
4→[CH
3(CH
2)
16COO]
2Mg+Na
2SO
4
The reason that adopts two-step reaction to prepare Magnesium Stearate is because stearic acid is a kind of weak acid, it can not generate Magnesium Stearate with the sal epsom direct reaction, can only be earlier stearic acid and sodium hydroxide reaction be made sodium stearate, and then sodium stearate solution and Adlerika reacted and make Magnesium Stearate.
In the method, the reaction of sodium hydroxide and stearic acid generates in the sodium stearate process will note 2 points: the one, the adding speed of strict control sodium hydroxide, and prevent that the solution boiling from overflowing; The 2nd, guarantee stearic acid and sodium hydroxide complete reaction.If stearic acid and sodium hydroxide reaction are not exclusively, then directly influence the content of MgO in the product, finally make product defective.
According to the requirement of Chinese Pharmacopoeia 2010 editions, the content of MgO should be 6.5-7.5% in the Magnesium Stearate.Utilize present method to produce the pharmaceutical excipient Magnesium Stearate, for guaranteeing MgO content conformance with standard, will control two key factors in the production:
(1) sodium hydroxide concentration is wanted strict 102-106% of the theoretical requirement that is controlled to be.If sodium hydroxide concentration is less than 102% of theoretical requirement, then stearic acid can not complete reaction generate sodium stearate, will make like this and contain a small amount of unreacted stearic acid particle in the product, and MgO content is lower than 6.5% in the product thereby make; If sodium hydroxide concentration is greater than 106% of theoretical requirement, then stearic acid and sodium hydroxide react remaining sodium hydroxide and will react the generation magnesium hydroxide with sal epsom in follow-up reaction, and MgO content is higher than 7.5% in the product thereby make.
(2) in the reaction of sodium stearate and sal epsom, the consumption of sal epsom will be controlled and be not less than 115% of theoretical consumption.Experiment shows: when the consumption of sal epsom be lower than theoretical consumption 114% the time, the content of MgO will be lower than 6.5% in the product; When the consumption of sal epsom be higher than theoretical consumption 126% the time, the content of MgO will no longer increase in the product.Therefore, the consumption of Magnesium Stearate should be controlled at 114-126% of theoretical consumption.
Deionized water large usage quantity in the described two-step reaction, the soluble impurity major part is soluble in water, and water consumption is more greatly to the not influence of water-fast Magnesium Stearate, so the color and luster of the pharmaceutical excipient Magnesium Stearate that present method makes is good.
Therefore, utilize the quality index of the pharmaceutical excipient Magnesium Stearate that present method produces stable, particularly the content of MgO can meet 2010 editions requirements of Chinese Pharmacopoeia, and manufacturing condition is easy to control, and product color is good.
As the optimization of present method, the 5th step describedly washed to adopting 25-40 ℃ deionized water that Magnesium Stearate crude product filter cake is washed Magnesium Stearate crude product filter cake.
The 5th step, described drying was not higher than 5.0%. for the water content that is dried to the pharmaceutical excipient Magnesium Stearate under 60-75 ℃ temperature
The Magnesium Stearate filter cake is washed to remove water-soluble impurity in the filter cake.Through repeatedly washing and centrifuge dehydration, until product water-soluble impurity index till check meets 2010 editions requirements of Chinese Pharmacopoeia, drying to water content is not higher than 5.0% again, and the content of MgO is 6.5-7.5% in the pharmaceutical excipient Magnesium Stearate that makes like this, and quality index is stable.
The main component of utilizing present method to produce the filtrate that the pharmaceutical excipient Magnesium Stearate produces is sodium sulfate, through filtrate is concentrated, crystallization can get sodium sulfate byproduct, sodium sulfate can be used as the toxinicide that laxative and barium salt are poisoned after purifying.
Embodiment
The invention will be further described below by specific embodiment:
Embodiment 1
The preparation method of pharmaceutical excipient Magnesium Stearate may further comprise the steps:
The first step: under whipped state, 0.14kg sodium hydroxide is dissolved in the 3L deionized water, continue to stir 15min after being warming up to 60 ℃, make sodium hydroxide solution, be incubated 70 ℃ stand-by;
Second step: under whipped state with the MgSO of 0. 4kg
47H
2O dissolves in the 14L deionized water, continue to stir 30min after being warming up to 75 ℃, makes Adlerika, be incubated 70 ℃ stand-by;
The 3rd step: the 1kg stearic acid is joined in the 15L deionized water, be heated to 85 ℃, stearic acid is dissolved fully be oily matter and float on liquid level; The sodium hydroxide solution that the first step is prepared slowly joins in the mixed solution of stearic acid and water under well-beaten condition, and reaction makes sodium stearate solution behind the 2h, be cooled to 70 ℃ stand-by;
The 4th step: prepared Adlerika of second step is slowly joined under whipped state in the prepared sodium stearate solution of the 3rd step, keep stirring 50min under 70 ℃ of conditions of temperature, be cooled to normal temperature then, leave standstill in the rotary and centrifugal machine that changes the band filter cloth behind the 8h over to and separate, get Magnesium Stearate crude product filter cake;
The 5th step: adopt 25-40 ℃ deionized water that Magnesium Stearate crude product filter cake is washed, dewaters repeatedly, after meeting the requirement of Chinese Pharmacopoeia 2010 editions to the water-soluble impurity index of Magnesium Stearate filter cake, under 60-75 ℃ temperature, carry out drying, be dried to water content and be not higher than 5.0%, namely get the pharmaceutical excipient Magnesium Stearate.
Embodiment 2
The preparation method of pharmaceutical excipient Magnesium Stearate may further comprise the steps:
The first step: under whipped state, 0.15kg sodium hydroxide is dissolved in the 3.5L deionized water, continue to stir 20min after being warming up to 70 ℃, make sodium hydroxide solution, be incubated 65 ℃ stand-by;
Second step: under whipped state with the MgSO of 0. 5kg
47H
2O dissolves in the 15L deionized water, continue to stir 20min after being warming up to 70 ℃, makes Adlerika, be incubated 65 ℃ stand-by;
The 3rd step: the 1kg stearic acid is joined in the 20L deionized water, be heated to 90 ℃, stearic acid is dissolved fully be oily matter and float on liquid level; The sodium hydroxide solution that the first step is prepared slowly joins in the mixed solution of stearic acid and water under well-beaten condition, and reaction makes sodium stearate solution behind the 2.5h, be cooled to 65 ℃ stand-by;
The 4th step: prepared Adlerika of second step is slowly joined under whipped state in the prepared sodium stearate solution of the 3rd step, keep stirring 70min under 65 ℃ of conditions of temperature, be cooled to normal temperature then, leave standstill in the rotary and centrifugal machine that changes the band filter cloth behind the 9h over to and separate, get Magnesium Stearate crude product filter cake;
The 5th step: adopt 25-40 ℃ deionized water that Magnesium Stearate crude product filter cake is washed, dewaters repeatedly, after meeting the requirement of Chinese Pharmacopoeia 2010 editions to the water-soluble impurity index of Magnesium Stearate filter cake, under 60-75 ℃ temperature, carry out drying, be dried to water content and be not higher than 5.0%, namely get the pharmaceutical excipient Magnesium Stearate.
Embodiment 3
The preparation method of pharmaceutical excipient Magnesium Stearate may further comprise the steps:
The first step: under whipped state, 0.16kg sodium hydroxide is dissolved in the 4L deionized water, continue to stir 25min after being warming up to 75 ℃, make sodium hydroxide solution, be incubated 75 ℃ stand-by;
Second step: under whipped state with the MgSO of 0. 6kg
47H
2O dissolves in the 16L deionized water, continue to stir 40min after being warming up to 65 ℃, makes Adlerika, be incubated 75 ℃ stand-by;
The 3rd step: the 1kg stearic acid is joined in the 25L deionized water, be heated to 95 ℃, stearic acid is dissolved fully be oily matter and float on liquid level; The sodium hydroxide solution that the first step is prepared slowly joins in the mixed solution of stearic acid and water under well-beaten condition, and reaction makes sodium stearate solution behind the 3h, be cooled to 75 ℃ stand-by;
The 4th step: prepared Adlerika of second step is slowly joined under whipped state in the prepared sodium stearate solution of the 3rd step, keep stirring 90min under 75 ℃ of conditions of temperature, be cooled to normal temperature then, leave standstill in the rotary and centrifugal machine that changes the band filter cloth behind the 10h over to and separate, get Magnesium Stearate crude product filter cake;
The 5th step: adopt 25-40 ℃ deionized water that Magnesium Stearate crude product filter cake is washed, dewaters repeatedly, after meeting the requirement of Chinese Pharmacopoeia 2010 editions to the water-soluble impurity index of Magnesium Stearate filter cake, under 60-75 ℃ temperature, carry out drying, be dried to water content and be not higher than 5.0%, namely get the pharmaceutical excipient Magnesium Stearate.
Claims (4)
1. the preparation method of pharmaceutical excipient Magnesium Stearate may further comprise the steps:
The first step: under whipped state, 0.14-0.16kg sodium hydroxide is dissolved in 3-4L deionized water, continue to stir 15-25min after being warming up to 60-75 ℃, make sodium hydroxide solution, be incubated 65-75 ℃ stand-by;
Second step: under whipped state with the MgSO of 0.4-0.6kg
47H
2O dissolves in 14-16L deionized water, continue to stir 20-40min after being warming up to 60-75 ℃, makes Adlerika, be incubated 65-75 ℃ stand-by;
The 3rd step: the 1kg stearic acid is joined in 15-25L deionized water, be heated to 85-95 ℃, stearic acid is dissolved fully be oily matter and float on liquid level; The sodium hydroxide solution that the first step is prepared slowly joins in the mixed solution of stearic acid and water under well-beaten condition, and reaction makes sodium stearate solution behind 2-3h, be cooled to 65-75 ℃ stand-by;
The 4th step: prepared Adlerika of second step is slowly joined under whipped state in the prepared sodium stearate solution of the 3rd step, keep stirring 50-90min under 65-75 ℃ of conditions of temperature, be cooled to normal temperature then, leave standstill in the rotary and centrifugal machine that changes the band filter cloth behind 8-10h over to and separate, get Magnesium Stearate crude product filter cake;
The 5th step: Magnesium Stearate crude product filter cake is washed, dewaters repeatedly, carry out drying meet the requirement of Chinese Pharmacopoeia 2010 editions to the water-soluble impurity index of Magnesium Stearate filter cake after, namely get the pharmaceutical excipient Magnesium Stearate.
2. the preparation method of pharmaceutical excipient Magnesium Stearate according to claim 1 is characterized in that: the 5th step is described washs to adopting 25-40 ℃ deionized water that Magnesium Stearate crude product filter cake is washed Magnesium Stearate crude product filter cake.
3. the preparation method of pharmaceutical excipient Magnesium Stearate according to claim 1 is characterized in that: the 5th step, described drying was for carrying out drying under 60-75 ℃ temperature.
4. according to the preparation method of the described pharmaceutical excipient Magnesium Stearate of claim 1 to 3, it is characterized in that: the content of MgO is 6.5-7.5% in the described pharmaceutical excipient Magnesium Stearate, water content is not higher than 5.0%.
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104529744A (en) * | 2014-12-22 | 2015-04-22 | 尹建 | Method for preparing magnesium stearate |
| CN104892399A (en) * | 2015-05-07 | 2015-09-09 | 溧阳市云凯化工有限公司 | Lithium stearate production process |
| CN104910005A (en) * | 2015-06-17 | 2015-09-16 | 德清县维康生物科技有限公司 | Magnesium stearate applicable to pharmaceutical preparations and preparation method thereof |
| CN105296195A (en) * | 2015-10-21 | 2016-02-03 | 广州立白企业集团有限公司 | Liquid detergent composition for in-situ generation of pearling agent particles |
| WO2016109856A1 (en) | 2015-01-02 | 2016-07-07 | Melaleuca, Inc. | Multi-supplement compositions |
| US10137164B2 (en) | 2015-01-02 | 2018-11-27 | Melaleuca, Inc. | Dietary supplement compositions |
| US10576112B2 (en) | 2015-01-02 | 2020-03-03 | Melaleuca, Inc. | Bacterial compositions |
| RU2790488C1 (en) * | 2022-05-29 | 2023-02-21 | Общество С Ограниченной Ответственностью "Научно - Исследовательский Институт Технологий Органической, Неорганической Химии И Биотехнологий" | Method for producing and purifying magnesium stearate |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102372620A (en) * | 2010-08-17 | 2012-03-14 | 安徽山河药用辅料股份有限公司 | Preparation method of magnesium stearate with improved specific volume and whiteness |
-
2013
- 2013-01-30 CN CN2013100363320A patent/CN103193614A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102372620A (en) * | 2010-08-17 | 2012-03-14 | 安徽山河药用辅料股份有限公司 | Preparation method of magnesium stearate with improved specific volume and whiteness |
Non-Patent Citations (1)
| Title |
|---|
| 秦玉楠: "药用硬脂酸镁制备工艺及其改进", 《现代应用药学》, vol. 8, no. 3, 30 June 1991 (1991-06-30) * |
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104529744A (en) * | 2014-12-22 | 2015-04-22 | 尹建 | Method for preparing magnesium stearate |
| WO2016109856A1 (en) | 2015-01-02 | 2016-07-07 | Melaleuca, Inc. | Multi-supplement compositions |
| US10137164B2 (en) | 2015-01-02 | 2018-11-27 | Melaleuca, Inc. | Dietary supplement compositions |
| US10576112B2 (en) | 2015-01-02 | 2020-03-03 | Melaleuca, Inc. | Bacterial compositions |
| US11207388B2 (en) | 2015-01-02 | 2021-12-28 | Melaleuca, Inc. | Multi-supplement compositions |
| US11273195B2 (en) | 2015-01-02 | 2022-03-15 | Melaleuca, Inc. | Dietary supplement compositions |
| US11433107B2 (en) | 2015-01-02 | 2022-09-06 | Melaleuca, Inc. | Bacterial compositions |
| CN104892399A (en) * | 2015-05-07 | 2015-09-09 | 溧阳市云凯化工有限公司 | Lithium stearate production process |
| CN104910005A (en) * | 2015-06-17 | 2015-09-16 | 德清县维康生物科技有限公司 | Magnesium stearate applicable to pharmaceutical preparations and preparation method thereof |
| CN105296195A (en) * | 2015-10-21 | 2016-02-03 | 广州立白企业集团有限公司 | Liquid detergent composition for in-situ generation of pearling agent particles |
| CN105296195B (en) * | 2015-10-21 | 2018-01-19 | 广州立白企业集团有限公司 | A kind of liquid detergent composition of in-situ preparation pearling agent particle |
| RU2790488C1 (en) * | 2022-05-29 | 2023-02-21 | Общество С Ограниченной Ответственностью "Научно - Исследовательский Институт Технологий Органической, Неорганической Химии И Биотехнологий" | Method for producing and purifying magnesium stearate |
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Application publication date: 20130710 |