CN113694032B - Methylprednisolone sodium succinate freeze-dried powder injection for injection and preparation method thereof - Google Patents
Methylprednisolone sodium succinate freeze-dried powder injection for injection and preparation method thereof Download PDFInfo
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- A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
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- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
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- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/08—Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock
Abstract
The invention relates to a methylprednisolone sodium succinate freeze-dried powder injection for injection and a preparation method thereof, belonging to the field of pharmaceutical preparations, wherein the lyophilized powder injection comprises methylprednisolone sodium succinate, a pH buffering agent and a stabilizing agent when the specification is 40mg, and the preparation method comprises the steps of adding the stabilizing agent into a disodium hydrogen phosphate-citric acid buffer solution, adding the methylprednisolone sodium succinate into a stirring solution, fixing the volume and shaking up to obtain a preparation solution, uniformly subpackaging the preparation solution into penicillin bottles, and freeze-drying to obtain a product; when the specification is more than or equal to 125mg, the methylprednisolone sodium succinate and the pH buffering agent are included, and the preparation method does not add a stabilizing agent. The methylprednisolone sodium succinate freeze-dried powder injection for injection prepared by the invention has good quality, high stability and low degradation rate in the storage process; the obtained product has short redissolution time by using 5% glucose injection.
Description
Technical Field
The invention relates to a methylprednisolone sodium succinate freeze-dried powder injection for injection and a preparation method thereof, belonging to the field of pharmaceutical preparations.
Background
Methylprednisolone is a middle-effect glucocorticoid medicine and has pharmacological actions of resisting inflammation, immunosuppression, antianaphylaxis, antishock and the like. The medicine has strong anti-inflammatory effect and weak water and sodium retention, and is widely applied clinically. The methylprednisolone sodium succinate is a water-soluble methylprednisolone derivative (prodrug), and the high-concentration aqueous solution is particularly suitable for treating diseases needing hormone treatment with strong action and quick response, but needs to be prepared into powder injection because the methylprednisolone sodium succinate is not stable in the aqueous solution and cannot be stored for a long time.
At present, methylprednisolone sodium succinate freeze-dried powder injection mostly takes methylprednisolone succinate as a raw material, methylprednisolone sodium succinate is generated through reaction in preparation, water-insoluble methylprednisolone is easily generated in the preparation and storage processes, the clarity after redissolution is influenced, the stability is poor, and compared with the original ground (American glimmer) product, the redissolution time of 5% glucose injection is longer, and the use of medical care personnel is influenced; in addition, studies have shown that long reconstitution times may lead to a lag in clinical efficacy or even ineffectiveness. Therefore, the product stability of the methylprednisolone sodium succinate freeze-dried powder injection for injection is improved, and the redissolution time of 5% glucose injection is shortened, so that the methylprednisolone sodium succinate freeze-dried powder injection has important clinical significance.
Disclosure of Invention
The invention aims to provide a methylprednisolone sodium succinate freeze-dried powder injection for injection and a preparation method thereof, and the obtained product has good stability and short redissolution time with 5% glucose injection.
In order to achieve the purpose, the invention adopts the technical scheme that:
a lyophilized powder for injection comprises methylprednisolone sodium succinate, pH buffer and stabilizer, when the specification is 40 mg; when the specification is more than or equal to 125mg, the composition comprises methylprednisolone sodium succinate and a pH buffering agent.
The technical scheme of the invention is further improved as follows: the pH buffering agent comprises disodium hydrogen phosphate and citric acid; the stabilizer is sucrose and/or lactose.
The technical scheme of the invention is further improved as follows: when the specification is 40mg, the formula of each freeze-dried powder injection is as follows: 53.0mg of methylprednisolone sodium succinate, 25mg of stabilizer, 18-27 mg of disodium hydrogen phosphate and 1-8 mg of citric acid; when the specification is more than or equal to 125mg, the formula of each freeze-dried powder injection is as follows: 165.7-1326.0 mg of methylprednisolone sodium succinate, 18-27 mg of disodium hydrogen phosphate and 1-8 mg of citric acid.
A method for preparing methylprednisolone sodium succinate freeze-dried powder injection for injection comprises the following steps:
(1) Preparing a disodium hydrogen phosphate-citric acid buffer solution for later use;
(2) When the specification is 40mg, adding a stabilizer into the buffer solution in the step (1), and stirring and dissolving for later use;
(3) Adding methylprednisolone sodium succinate into the solution in the step (1) or the step (2), stirring until the solution is clear, adding water for injection to a constant volume, and shaking up to obtain a preparation solution;
(4) Uniformly subpackaging the prepared solution obtained in the step (3) into penicillin bottles, and semi-pressing rubber plugs to obtain samples to be freeze-dried;
(5) And (5) freeze-drying the sample to be freeze-dried obtained in the step (4), capping and packaging to obtain a finished product.
The technical scheme of the invention is further improved as follows: the freeze-drying process in the step (5) is that the temperature of a freeze dryer is reduced from room temperature to-35 ℃ to-50 ℃, then a sample to be freeze-dried is placed in the freeze dryer, and the temperature is kept for 2-4 hours; then heating to-10-20 ℃, controlling the vacuum degree at 0.1-0.3 mbar, and preserving heat for 6-15 h; finally, the temperature is increased to 30-40 ℃, the vacuum degree is controlled to be 0.1-0.3 mbar, and the temperature is kept for 2-4 hours.
The technical scheme of the invention is further improved as follows: the pH value of the buffer solution in the step (1) is 6.0-8.0.
Due to the adoption of the technical scheme, the invention has the following technical effects:
the methylprednisolone sodium succinate freeze-dried powder injection for injection prepared by the invention has the advantages of good quality, high stability and low degradation rate in the storage process.
The methylprednisolone sodium succinate freeze-dried powder injection for injection prepared by the invention has good solubility, short redissolution time by using 5% glucose injection, and shortened medicine dissolution time of medical personnel in the using process.
The preparation method has simple steps and simple conditions, and is beneficial to industrial production.
Detailed Description
The present invention will be described in further detail with reference to specific examples below:
a methylprednisolone sodium succinate lyophilized powder for injection, when the specification is 40mg, the formula of each lyophilized powder for injection is as follows: 53.0mg of methylprednisolone sodium succinate, 25mg of stabilizer, 18-27 mg of disodium hydrogen phosphate and 1-8 mg of citric acid, wherein the stabilizer is sucrose and/or lactose; when the specification is more than or equal to 125mg, the formula of each freeze-dried powder injection is as follows: 165.7-1326.0 mg of methylprednisolone sodium succinate, 18-27 mg of disodium hydrogen phosphate and 1-8 mg of citric acid.
A method for preparing methylprednisolone sodium succinate freeze-dried powder injection for injection comprises the following steps:
(1) Preparing a disodium hydrogen phosphate-citric acid buffer solution with the pH value of 6.0-8.0 for later use;
(2) When the specification is 40mg, adding a stabilizing agent into the buffer solution in the step (1), and stirring and dissolving for later use;
(3) Adding methylprednisolone sodium succinate into the solution in the step (1) or the step (2), stirring until the solution is clear, adding water for injection to a constant volume, and shaking up to obtain a preparation solution;
(4) Uniformly subpackaging the prepared solution obtained in the step (3) into penicillin bottles, and semi-pressing rubber plugs to obtain samples to be freeze-dried;
(5) Firstly, cooling the temperature of a freeze dryer from room temperature to-35 to-50 ℃, then placing the sample to be freeze-dried obtained in the step (4), and preserving the heat for 2-4 hours; then heating to-10-20 ℃, controlling the vacuum degree at 0.1-0.3 mbar, and preserving heat for 6-15 h; finally, the temperature is raised to 30 to 40 ℃, the vacuum degree is controlled to be 0.1 to 0.3mbar, and the temperature is kept for 2 to 4 hours.
Example 1
A methylprednisolone sodium succinate freeze-dried powder injection for injection is 40mg, and the formula of each freeze-dried powder injection is as follows: 53.0mg of methylprednisolone sodium succinate, 25mg of lactose, 23mg of disodium hydrogen phosphate and 4mg of citric acid.
The preparation method comprises the following steps of:
(1) Weighing 2300mg of disodium hydrogen phosphate (anhydrous) and 400mg of citric acid, and adding 80ml of water for injection to prepare a disodium hydrogen phosphate-citric acid buffer solution with the pH value of 7.0 for later use;
(2) Adding 2500mg of lactose into the buffer solution in the step (1), and stirring for dissolving for later use;
(3) Adding 5300mg of methylprednisolone sodium succinate into the solution in the step (2), stirring until the solution is clear, adding water for injection to fix the volume to 100ml, and shaking up to obtain a preparation solution;
(4) Subpackaging the prepared solution obtained in the step (3) into penicillin bottles according to the standard of 1 ml/bottle, and semi-pressing rubber plugs to obtain samples to be lyophilized;
(5) Cooling the freeze dryer from room temperature to-35-50 ℃, then putting the sample to be freeze-dried obtained in the step (4), and keeping the temperature for 2-4h; then heating to-10-20 ℃, controlling the vacuum degree at 0.1-0.3 mbar, and preserving heat for 6-15 h; finally, the temperature is increased to 30-40 ℃, the vacuum degree is controlled to be 0.1-0.3 mbar, and the temperature is kept for 2-4 hours.
Example 2
A methylprednisolone sodium succinate freeze-dried powder injection for injection is 40mg, and the formula of each freeze-dried powder injection is as follows: 53.0mg of methylprednisolone sodium succinate, 25mg of cane sugar, 23mg of disodium hydrogen phosphate and 4mg of citric acid.
The preparation method comprises the following steps of:
(1) Weighing 2300mg of disodium hydrogen phosphate (anhydrous) and 400mg of citric acid, and adding 80ml of water for injection to prepare a disodium hydrogen phosphate-citric acid buffer solution with the pH value of 7.0 for later use;
(2) Adding 2500mg of sucrose into the buffer solution in the step (1), and stirring and dissolving for later use;
(3) Adding 5300mg of methylprednisolone sodium succinate into the solution in the step (2), stirring until the solution is clear, adding water for injection to fix the volume to 100ml, and shaking up to obtain a preparation solution;
(4) Subpackaging the prepared solution obtained in the step (3) into penicillin bottles according to the standard of 1 ml/bottle, and semi-pressing rubber plugs to obtain samples to be freeze-dried;
(5) Cooling the freeze dryer from room temperature to-35-50 ℃, then putting the sample to be freeze-dried obtained in the step (4), and keeping the temperature for 2-4h; then heating to-10-20 deg.C, controlling the vacuum degree at 0.1-0.3 mbar, and keeping the temperature for 6-15 h; finally, the temperature is raised to 30 to 40 ℃, the vacuum degree is controlled to be 0.1 to 0.3mbar, and the temperature is kept for 2 to 4 hours.
Example 3
The specification of the methylprednisolone sodium succinate freeze-dried powder injection for injection is 40mg, and the formula of each freeze-dried powder injection comprises the following components: 53.0mg of methylprednisolone sodium succinate, 12.5mg of lactose, 12.5mg of cane sugar, 23mg of disodium hydrogen phosphate and 4mg of citric acid.
The preparation method comprises the following steps of:
(1) Weighing 2300mg of disodium hydrogen phosphate (anhydrous) and 400mg of citric acid, and adding 80ml of water for injection to prepare a disodium hydrogen phosphate-citric acid buffer solution with the pH of 7.0 for later use;
(2) Adding 1250mg of lactose and 1250mg of sucrose into the buffer solution in the step (1), and stirring and dissolving for later use;
(3) Adding 5300mg of methylprednisolone sodium succinate into the solution in the step (2), stirring until the solution is clear, adding water for injection to fix the volume to 100ml, and shaking up to obtain a preparation solution;
(4) Subpackaging the prepared solution obtained in the step (3) into penicillin bottles according to the standard of 1 ml/bottle, and semi-pressing rubber plugs to obtain samples to be lyophilized;
(5) Cooling the freeze dryer from room temperature to-35-50 ℃, then putting the sample to be freeze-dried obtained in the step (4), and keeping the temperature for 2-4h; then heating to-10-20 ℃, controlling the vacuum degree at 0.1-0.3 mbar, and preserving heat for 6-15 h; finally, the temperature is increased to 30-40 ℃, the vacuum degree is controlled to be 0.1-0.3 mbar, and the temperature is kept for 2-4 hours.
Example 4
The specification of the methylprednisolone sodium succinate freeze-dried powder injection for injection is 40mg, and the formula of each freeze-dried powder injection comprises the following components: 53.0mg of methylprednisolone sodium succinate, 12.5mg of lactose, 12.5mg of cane sugar, 18mg of disodium hydrogen phosphate and 8mg of citric acid.
The preparation method comprises the following steps of:
(1) Weighing 1800mg of disodium hydrogen phosphate (anhydrous) and 800mg of citric acid, and adding 80ml of water for injection to prepare a disodium hydrogen phosphate-citric acid buffer solution with the pH value of 6.0 for later use;
(2) Adding 1250mg of lactose and 1250mg of sucrose into the buffer solution in the step (1), and stirring and dissolving for later use;
(3) Adding 5300mg of methylprednisolone sodium succinate into the solution in the step (2), stirring until the solution is clear, adding water for injection to fix the volume to 100ml, and shaking up to obtain a preparation solution;
(4) Subpackaging the prepared solution obtained in the step (3) into penicillin bottles according to the standard of 1 ml/bottle, and semi-pressing rubber plugs to obtain samples to be lyophilized;
(5) Firstly, cooling the temperature of a freeze dryer from room temperature to-35 to-50 ℃, then placing the sample to be freeze-dried obtained in the step (4), and preserving the heat for 2-4h; then heating to-10-20 ℃, controlling the vacuum degree at 0.1-0.3 mbar, and preserving heat for 6-15 h; finally, the temperature is raised to 30 to 40 ℃, the vacuum degree is controlled to be 0.1 to 0.3mbar, and the temperature is kept for 2 to 4 hours.
Example 5
A methylprednisolone sodium succinate freeze-dried powder injection for injection is 40mg, and the formula of each freeze-dried powder injection is as follows: 53.0mg of methylprednisolone sodium succinate, 12.5mg of lactose, 12.5mg of cane sugar, 27mg of disodium hydrogen phosphate and 1mg of citric acid.
The preparation method comprises the following steps of:
(1) Weighing 2700mg of disodium hydrogen phosphate (anhydrous) and 100mg of citric acid, and adding 80ml of water for injection to prepare a disodium hydrogen phosphate-citric acid buffer solution with the pH value of 7.8 for later use;
(2) Adding 1250mg of lactose and 1250mg of sucrose into the buffer solution in the step (1), and stirring and dissolving for later use;
(3) Adding 5300mg of methylprednisolone sodium succinate into the solution in the step (2), stirring until the solution is clear, adding water for injection to fix the volume to 100ml, and shaking up to obtain a preparation solution;
(4) Subpackaging the prepared solution obtained in the step (3) into penicillin bottles according to the standard of 1 ml/bottle, and semi-pressing rubber plugs to obtain samples to be freeze-dried;
(5) Firstly, cooling the temperature of a freeze dryer from room temperature to-35 to-50 ℃, then placing the sample to be freeze-dried obtained in the step (4), and preserving the heat for 2-4h; then heating to-10-20 deg.C, controlling the vacuum degree at 0.1-0.3 mbar, and keeping the temperature for 6-15 h; finally, the temperature is increased to 30-40 ℃, the vacuum degree is controlled to be 0.1-0.3 mbar, and the temperature is kept for 2-4 hours.
Example 6
The specification of the methylprednisolone sodium succinate freeze-dried powder injection for injection is 125mg, and the formula of each freeze-dried powder injection comprises the following components: 165.7mg of methylprednisolone sodium succinate, 23mg of disodium hydrogen phosphate and 4mg of citric acid.
The preparation method comprises the following steps of:
(1) Weighing 2300mg of disodium hydrogen phosphate (anhydrous) and 400mg of citric acid, and adding 160ml of water for injection to prepare a disodium hydrogen phosphate-citric acid buffer solution with the pH value of 7.0 for later use;
(2) Adding 16.57g of methylprednisolone sodium succinate into the solution in the step (2), stirring until the solution is clear, adding water for injection to constant volume of 200ml, and shaking up to obtain a preparation solution;
(3) Subpackaging the prepared solution obtained in the step (2) into penicillin bottles according to the standard of 2 ml/bottle, and semi-pressing rubber plugs to obtain samples to be lyophilized;
(4) Cooling the freeze dryer from room temperature to-35-50 ℃, then putting the sample to be freeze-dried obtained in the step (3), and keeping the temperature for 2-4h; then heating to-10-20 deg.C, controlling the vacuum degree at 0.1-0.3 mbar, and keeping the temperature for 6-15 h; finally, the temperature is raised to 30 to 40 ℃, the vacuum degree is controlled to be 0.1 to 0.3mbar, and the temperature is kept for 2 to 4 hours.
Example 7
A methylprednisolone sodium succinate freeze-dried powder injection for injection is 500mg, and the formula of each freeze-dried powder injection is as follows: 663.0mg of methylprednisolone sodium succinate, 18mg of disodium hydrogen phosphate and 8mg of citric acid.
The preparation method comprises the following steps of:
(1) Weighing 1800mg of disodium hydrogen phosphate (anhydrous) and 800mg of citric acid, and adding 640ml of water for injection to prepare a disodium hydrogen phosphate-citric acid buffer solution with the pH value of 6.0 for later use;
(2) Adding 66.30g of methylprednisolone sodium succinate into the solution in the step (2), stirring until the solution is clear, adding water for injection to fix the volume to 800ml, and shaking up to obtain a preparation solution;
(3) Subpackaging the prepared solution obtained in the step (2) into penicillin bottles according to the standard of 8 ml/bottle, and semi-pressing rubber plugs to obtain samples to be lyophilized;
(4) Cooling the freeze dryer from room temperature to-35-50 ℃, then putting the sample to be freeze-dried obtained in the step (3), and keeping the temperature for 2-4h; then heating to-10-20 ℃, controlling the vacuum degree at 0.1-0.3 mbar, and preserving heat for 6-15 h; finally, the temperature is raised to 30 to 40 ℃, the vacuum degree is controlled to be 0.1 to 0.3mbar, and the temperature is kept for 2 to 4 hours.
Example 8
A methylprednisolone sodium succinate lyophilized powder for injection with specification of 1000mg, each lyophilized powder for injection has a formula of: 1326.0mg of methylprednisolone sodium succinate, 27mg of disodium hydrogen phosphate and 1mg of citric acid.
The preparation method comprises the following steps of:
(1) Weighing 2700mg of disodium hydrogen phosphate (anhydrous) and 100mg of citric acid, and adding 1280ml of water for injection to prepare a disodium hydrogen phosphate-citric acid buffer solution with the pH of 7.8 for later use;
(2) Adding 132.60g of methylprednisolone sodium succinate into the solution in the step (2), stirring until the solution is clear, adding water for injection to a constant volume of 1600ml, and shaking up to obtain a preparation solution;
(3) Subpackaging the prepared solution obtained in the step (2) into penicillin bottles according to the standard of 16 ml/bottle, and semi-pressing rubber plugs to obtain samples to be lyophilized;
(4) Firstly, cooling the temperature of a freeze dryer from room temperature to-35 to-50 ℃, then placing the sample to be freeze-dried obtained in the step (3), and preserving the heat for 2-4h; then heating to-10-20 ℃, controlling the vacuum degree at 0.1-0.3 mbar, and preserving heat for 6-15 h; finally, the temperature is increased to 30-40 ℃, the vacuum degree is controlled to be 0.1-0.3 mbar, and the temperature is kept for 2-4 hours.
Comparative example 1
A methylprednisolone sodium succinate freeze-dried powder injection for injection is 40mg, and the formula of each freeze-dried powder injection is as follows: 53.0mg of methylprednisolone sodium succinate, 25mg of lactose, 17.46mg of disodium hydrogen phosphate and 1.6mg of sodium dihydrogen phosphate monohydrate.
The preparation method comprises the following steps of:
(1) 1746mg of disodium hydrogen phosphate (anhydrous) and 160mg of sodium dihydrogen phosphate monohydrate are weighed, and 80ml of water for injection is added to prepare a disodium hydrogen phosphate-sodium dihydrogen phosphate buffer solution with the pH value of 7.0 for later use;
(2) Adding 2500mg of lactose into the buffer solution in the step (1), and stirring for dissolving for later use;
(3) Adding 5300mg of methylprednisolone sodium succinate into the solution in the step (2), stirring until the solution is clear, adding water for injection to fix the volume to 100ml, and shaking up to obtain a preparation solution;
(4) Subpackaging the prepared solution obtained in the step (3) into penicillin bottles according to the standard of 1 ml/bottle, and semi-pressing rubber plugs to obtain samples to be freeze-dried;
(5) Firstly, cooling the temperature of a freeze dryer from room temperature to-35 to-50 ℃, then placing the sample to be freeze-dried obtained in the step (4), and preserving the heat for 2-4h; then heating to-10-20 ℃, controlling the vacuum degree at 0.1-0.3 mbar, and preserving heat for 6-15 h; finally, the temperature is increased to 30-40 ℃, the vacuum degree is controlled to be 0.1-0.3 mbar, and the temperature is kept for 2-4 hours.
Comparative example 2
The specification of the methylprednisolone sodium succinate freeze-dried powder injection for injection is 125mg, and the formula of each freeze-dried powder injection comprises the following components: 165.7mg of methylprednisolone sodium succinate, 17.46mg of disodium hydrogen phosphate and 1.6mg of sodium dihydrogen phosphate monohydrate.
The preparation method comprises the following steps of:
(1) Weighing 1746mg of disodium hydrogen phosphate (anhydrous) and 160mg of sodium dihydrogen phosphate monohydrate, and adding 160ml of water for injection to prepare a disodium hydrogen phosphate-sodium dihydrogen phosphate buffer solution with the pH value of 7.0 for later use;
(2) Adding 16.57g of methylprednisolone sodium succinate into the solution in the step (2), stirring until the solution is clear, adding water for injection to a constant volume of 200ml, and shaking up to obtain a preparation solution;
(3) Subpackaging the prepared solution obtained in the step (2) into penicillin bottles according to the standard of 2 ml/bottle, and semi-pressing rubber plugs to obtain samples to be freeze-dried;
(4) Cooling the freeze dryer from room temperature to-35-50 ℃, then putting the sample to be freeze-dried obtained in the step (3), and keeping the temperature for 2-4h; then heating to-10-20 ℃, controlling the vacuum degree at 0.1-0.3 mbar, and preserving heat for 6-15 h; finally, the temperature is raised to 30 to 40 ℃, the vacuum degree is controlled to be 0.1 to 0.3mbar, and the temperature is kept for 2 to 4 hours.
Comparative example 3
125mg of methylprednisolone sodium succinate freeze-dried powder injection for injection is prepared according to the patent CN104434820A in the example 1.
Table 1 shows the product stability comparison results of examples and comparative examples:
TABLE 1
Note: a-illumination for 10 days, B-60 ℃ for 10 days.
As can be seen from table 1 above: compared with the products of the comparative example and the products sold on the market, the products of the embodiment have high stability, and the growth rate of the free methylprednisolone and the total impurities is low; especially, the stability of the product is best when the pH of the product is 7.8.
Table 2 shows the comparative results of the products of the examples and the control examples reconstituted with 5% glucose injection:
TABLE 2
As can be seen from table 2 above: the 5% glucose injection of the product of the example has a remarkable tendency of shortening the redissolution time, which is obviously shorter than that of the original product (pfeiri).
Claims (4)
1. A methylprednisolone sodium succinate freeze-dried powder injection for injection is characterized in that: when the specification is 40mg, the composition comprises methylprednisolone sodium succinate, a pH buffering agent and a stabilizing agent; when the specification is more than or equal to 125mg, the methylprednisolone sodium succinate and the pH buffering agent are included; the pH buffering agent comprises disodium hydrogen phosphate and citric acid; the stabilizing agent is sucrose and/or lactose;
when the specification is 40mg, the formula of each freeze-dried powder injection is as follows: 53.0mg of methylprednisolone sodium succinate, 25mg of stabilizer, 18-27 mg of disodium hydrogen phosphate and 1-8 mg of citric acid; when the specification is more than or equal to 125mg, the formula of each freeze-dried powder injection is as follows: 165.7-1326.0 mg of methylprednisolone sodium succinate, 18-27 mg of disodium hydrogen phosphate and 1-8 mg of citric acid.
2. The method for preparing the methylprednisolone sodium succinate freeze-dried powder injection for injection as claimed in claim 1, is characterized in that: the method comprises the following steps:
(1) Preparing a disodium hydrogen phosphate-citric acid buffer solution for later use;
(2) When the specification is 40mg, adding a stabilizing agent into the buffer solution in the step (1), and stirring and dissolving for later use;
(3) Adding methylprednisolone sodium succinate into the solution in the step (1) or the step (2), stirring until the solution is clear, adding water for injection to a constant volume, and shaking up to obtain a preparation solution;
(4) Uniformly subpackaging the prepared solution obtained in the step (3) into penicillin bottles, and semi-pressing rubber plugs to obtain samples to be lyophilized;
(5) And (5) freeze-drying the sample to be freeze-dried obtained in the step (4), capping and packaging to obtain a finished product.
3. The method for preparing the methylprednisolone sodium succinate freeze-dried powder injection for injection according to claim 2, which is characterized in that: the freeze-drying process in the step (5) is that the temperature of a freeze dryer is reduced from room temperature to-35 ℃ to-50 ℃, then a sample to be freeze-dried is placed in the freeze dryer, and the temperature is kept for 2-4 hours; then heating to-10-20 deg.C, controlling the vacuum degree at 0.1-0.3 mbar, and keeping the temperature for 6-15 h; finally, the temperature is increased to 30-40 ℃, the vacuum degree is controlled to be 0.1-0.3 mbar, and the temperature is kept for 2-4 hours.
4. The method for preparing the methylprednisolone sodium succinate freeze-dried powder injection for injection according to claim 2, which is characterized in that: the pH value of the buffer solution in the step (1) is 6.0-8.0.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1850089A (en) * | 2006-04-19 | 2006-10-25 | 天津药业焦作有限公司 | Methylprednisolone sodium succinate lyophilized composition and its preparing method |
| CN104434820A (en) * | 2014-11-20 | 2015-03-25 | 杭州澳亚生物技术有限公司 | Preparation method for methylprednisolone sodium succinate freeze-dried powder injection for injection |
| CN111249240A (en) * | 2020-02-24 | 2020-06-09 | 武汉人福药业有限责任公司 | Methylprednisolone sodium succinate powder injection for injection and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| GR1009641B (en) * | 2018-06-18 | 2019-11-12 | Laboserve Φαρμακευτικη Βιομηχανια Α.Ε. | Orally-administrated methylprednisolone sodium succinate-containing compositions |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1850089A (en) * | 2006-04-19 | 2006-10-25 | 天津药业焦作有限公司 | Methylprednisolone sodium succinate lyophilized composition and its preparing method |
| CN104434820A (en) * | 2014-11-20 | 2015-03-25 | 杭州澳亚生物技术有限公司 | Preparation method for methylprednisolone sodium succinate freeze-dried powder injection for injection |
| CN111249240A (en) * | 2020-02-24 | 2020-06-09 | 武汉人福药业有限责任公司 | Methylprednisolone sodium succinate powder injection for injection and preparation method thereof |
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