CN111643460A - Pantoprazole sodium freeze-dried preparation, preparation method thereof and injection preparation prepared from pantoprazole sodium freeze-dried preparation - Google Patents
Pantoprazole sodium freeze-dried preparation, preparation method thereof and injection preparation prepared from pantoprazole sodium freeze-dried preparation Download PDFInfo
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Abstract
The invention discloses a pantoprazole sodium freeze-dried preparation, a preparation method thereof and an injection prepared from the pantoprazole sodium freeze-dried preparation. The preparation method comprises the following steps: uniformly mixing pantoprazole sodium and auxiliary materials, and freeze-drying, wherein the freeze-drying step comprises prefreezing, first drying and resolution drying, the first drying comprises vacuumizing the prefreezed product, adding nitrogen, heating to-11 to-13 ℃, and keeping for 9-11 h; heating to-4-6 deg.C, and maintaining for 3-5 h; rapidly heating to-2 ℃, and preserving heat for 1-2 h; the analysis and drying comprises quickly heating to 9-11 deg.C, and maintaining for 2-4 h; then the temperature is increased to 28-30 ℃ and kept for 1-3 h; vacuumizing to limit, and keeping the temperature. The pantoprazole sodium freeze-dried preparation provided by the invention has the advantages of good stability and low impurity content, and the freeze-drying time of the preparation method is short.
Description
Technical Field
The invention belongs to the field of pharmaceutical preparations, and particularly relates to a pantoprazole sodium freeze-dried preparation, a preparation method thereof and an injection preparation prepared from the pantoprazole sodium freeze-dried preparation.
Background
Pantoprazole Sodium (Pantoprazole Sodium) with the chemical name: 5-Difluoromethoxy-2- [ (3, 4-dimethoxy-2-pyridyl) -methyl ] -sulfinyl-1H-benzimidazole sodium salt. The traditional Chinese medicine composition is clinically used for treating duodenal ulcer, gastric ulcer and Zollinger syndrome and relieving moderate-to-severe reflux esophagitis, and has the advantages of high cure rate and high cure speed. Pantoprazole sodium has poor stability and is sensitive to light, heat, oxygen, water and the like, and particularly under an acidic condition, the chemical structure of pantoprazole sodium can be destructively changed, and the phenomena of color change and polymerization occur, so that pantoprazole sodium is not suitable for being prepared into an aqueous solution for injection and is suitable for being prepared into a freeze-dried powder injection.
However, due to the extremely unstable property of pantoprazole sodium, even if the pantoprazole sodium is prepared into a freeze-dried preparation, quality problems such as color change and the like are easily caused in the processes of transportation and storage. Various preparation methods of pantoprazole sodium freeze-dried preparations are disclosed, different freeze-drying processes in the freeze-drying process have important influence on the quality of finished products (such as the water content and the property of the freeze-dried preparations, the clarity and the color of the re-dissolved solution, the components of related substances and the like), and the common freeze-drying process needs to remove water through long-time drying, so that the time is long.
Therefore, a preparation method, especially a freeze-drying process, of the pantoprazole sodium freeze-dried preparation needs to be developed, so that a freeze-dried preparation product with good stability, good re-solubility and low water content and related substance content is prepared, and meanwhile, the freeze-drying time is shortened.
Disclosure of Invention
The invention aims to overcome the defects of instability and long freeze-drying time of a pantoprazole sodium freeze-dried preparation in the prior art, and provides the pantoprazole sodium freeze-dried preparation, a preparation method thereof and an injection prepared from the pantoprazole sodium freeze-dried preparation. The pantoprazole sodium freeze-dried preparation provided by the invention has the advantages of good stability, good redissolution property and low impurity content, and the provided preparation method has the advantage of short freeze-drying time.
The present invention solves the above technical problems by the following means.
The preparation method of the pantoprazole sodium freeze-dried preparation comprises the following steps: uniformly mixing pantoprazole sodium with auxiliary materials, and freeze-drying, wherein the freeze-drying comprises the following steps:
1) pre-freezing: reducing the temperature to-40-45 ℃, and keeping the temperature for 2.5-3.5h to obtain a pre-frozen product;
2) primary drying: vacuumizing the pre-frozen product, adding nitrogen, heating to-11 to-13 ℃, keeping the temperature for 40-60min, and keeping for 9-11 h; heating to-4-6 deg.C for 50-70min for 3-5 h; heating to-2 ℃ at the speed of 1.0-1.5 ℃/min, and preserving heat for 1-2 h.
3) And (3) resolving and drying: raising the temperature to 9-11 ℃ at the speed of 0.9-1.1 ℃/min, and keeping the temperature for 2-4 h; heating to 28-32 deg.C for 10-20min, and maintaining for 1-3 hr; vacuumizing to limit vacuum, and keeping the temperature for 0.4-0.8 h.
Preferably, the pantoprazole sodium is pantoprazole sodium sesquihydrate and the molecular formula is C16H14F2N3NaO4S·1.5H2O。
Preferably, the auxiliary materials comprise a stabilizer, a pH regulator and water; more preferably, the stabilizing agent is disodium edetate for injection, and the pH regulator is sodium hydroxide; the water is water for injection.
In the present invention, the operation of uniformly mixing is a conventional liquid preparation process in the art, and preferably comprises the following steps:
adjusting the temperature of the water for injection to be below 30 ℃, introducing nitrogen, sequentially adding the disodium edetate, the sodium hydroxide and the pantoprazole sodium sesquihydrate, and supplementing the rest water.
In a preferred embodiment of the present application, the operation of uniformly mixing comprises the following steps: adding injection water according to 95% of the injection water in the prescription amount, cooling the injection water to below 30 ℃, filling nitrogen, weighing edetate disodium according to the prescription amount into a liquid preparation tank, and circularly stirring for at least 5min until the edetate disodium is completely dissolved; adding a part of sodium hydroxide solution, and circularly stirring for at least 5min until the sodium hydroxide solution is completely dissolved; adding pantoprazole sodium sesquihydrate according to the prescription amount, and circularly stirring for at least 20min until the pantoprazole sodium sesquihydrate is completely dissolved; adding water for injection to full volume, and circularly stirring for at least 20min until uniformly mixed; adjusting the pH value of the liquid medicine to 10.0-11.5 by using the other part of sodium hydroxide solution; the sum of the amounts of the sodium hydroxide solution added twice is equal to the amount prescribed.
In the present invention, after the uniform mixing and before the lyophilization, the filtration and canning operations are preferably performed. The filtration apparatus is preferably a 0.22 μm microfiltration membrane filter.
Preferably, the step of pre-freezing comprises: the temperature was reduced to-45 ℃ and held for 3 h. If the holding time is too long (e.g., greater than 3.5 hours), the time for sublimation drying may increase.
Preferably, the pressure of the system after said operation of incorporating nitrogen is 0.2 mbar.
Preferably, the first drying step comprises: vacuumizing the pre-frozen sample, adding nitrogen, heating to-12 ℃ under the pressure of 0.2mbar, heating for 50min, and keeping for 10 h; keeping the vacuum pressure unchanged, heating to-5 ℃, and keeping the temperature for 4 hours, wherein the heating time is 60 min; heating to 0 ℃ at the speed of 1 ℃/min, and preserving heat for 2 h.
Preferably, the desorption drying is as follows: heating to 10 ℃ at the speed of 1 ℃/min, and keeping the temperature for 3 h; heating to 30 deg.C for 10-20min, and maintaining for 2 hr; vacuumizing at 30 deg.C, and maintaining for 0.5 hr.
The pressure for ultimate vacuum pumping can be selected conventionally according to the performance of the equipment, and is preferably 0-0.1 MPa.
Preferably, the method also comprises the step of conducting pressure rise test after the analysis drying, and when the pressure rise rate is less than or equal to 0.02mbar/min, conducting pressure plug under the condition of filling nitrogen.
In the invention, the pantoprazole sodium freeze-dried preparation is in a form of pantoprazole sodium freeze-dried powder injection which is conventionally understood in the field.
Further, the invention also provides a pantoprazole sodium freeze-dried preparation which is prepared by the preparation method of the pantoprazole sodium freeze-dried preparation.
Further, the invention also provides a pantoprazole sodium injection prepared by re-dissolving the pantoprazole sodium freeze-dried preparation.
Wherein, the solvent used for the re-dissolution is a substance which is conventional in the field, such as water.
On the basis of the common knowledge in the field, the above preferred conditions can be combined randomly to obtain the preferred embodiments of the invention.
The reagents and starting materials used in the present invention are commercially available.
The positive progress effects of the invention are as follows: 1) by doping nitrogen instead of air in the first drying and analyzing and drying processes, the product quality is more stable, and the quality of the product is kept unchanged for a long time (within the validity period); 2) by adopting the gradual temperature rise program in the first drying process suitable for the specific product, the freeze-drying time is shortened, the forming and color of the freeze-dried product are improved, and the properties of the freeze-dried product, the clarity, the color and the like of the redissolved solution are stable; 3) if the temperature of the analysis drying is too low, the required freeze-drying time is longer, and the temperature of the analysis drying is too high, so that the quality of the product is influenced; meanwhile, compared with the common freeze-dried product, the freeze-drying time is shortened by removing water through long-time analysis and drying.
Detailed Description
The invention is further illustrated by the following examples, which are not intended to limit the scope of the invention. The experimental methods without specifying specific conditions in the following examples were selected according to the conventional methods and conditions, or according to the commercial instructions.
Example 1 preparation of pantoprazole sodium lyophilized preparation for injection
In example 1, lots 1, 2 and 3 are different lots of the product made by the method of example 1.
The formulation is shown in the following table 1:
TABLE 1 product recipe
| Raw and auxiliary materials | Unit dose |
| Pantoprazole sodium sesquihydrate | 45.1mg |
| Edetate disodium (for injection) | 1mg |
| Sodium hydroxide | 0.24mg |
| Water for injection | Adding to 2ml |
Taking injection water to below 30 ℃, introducing nitrogen, adding the injection water according to 95% of the injection water in the amount of the prescription, cooling the injection water to below 30 ℃, introducing the nitrogen, weighing edetate disodium according to the amount of the prescription into a preparation tank, and circularly stirring for at least 5min until the edetate disodium is completely dissolved; adding a part of sodium hydroxide solution, and circularly stirring for at least 5min until the sodium hydroxide solution is completely dissolved; adding pantoprazole sodium sesquihydrate according to the prescription amount, and circularly stirring for at least 20min until the pantoprazole sodium sesquihydrate is completely dissolved; adding water for injection to full volume, and circularly stirring for at least 20min until uniformly mixed; adjusting the pH value of the liquid medicine to 10.0-11.5 by using the other part of sodium hydroxide solution; the sum of the amounts of the sodium hydroxide solution added twice is equal to the amount prescribed. After the solution preparation, the solution is filtered by three 0.22 mu m microporous membrane filters, filled and freeze-dried.
The freeze-drying step specifically comprises: 1) pre-freezing: pre-cooling to 5-10 ℃ by a freeze dryer, and conveying the filled and half-plugged sample into the freeze dryer for freeze drying; opening a freeze dryer for pre-freezing, keeping for 2 hours when the temperature of the heat conducting oil is reduced to-45 ℃, cooling by a cold trap, vacuumizing, and starting primary drying when the vacuum degree is reduced to 0.2 mbar; 2) primary drying: nitrogen is doped in the drying process, the pressure is maintained at 0.2mbar, the temperature of the heat conducting oil is raised to-12 ℃ during primary drying, the temperature rise time is about 50min, and the temperature is kept for about 10 h; keeping the vacuum pressure unchanged, heating to-5 ℃, keeping the temperature for about 1h, and keeping the temperature for about 4 h; heating to 0 ℃ at the speed of 1.0-1.5 ℃/min, and keeping the temperature for 2 h; 3) and (3) resolving and drying: the vacuum pressure is unchanged, the temperature of the heat-conducting oil is increased to 10 ℃ at the speed of 0.9-1.1 ℃/min during analysis and drying, and the heat preservation time is 3 h; the temperature is raised to 30 ℃ for about 15min and kept for about 2 h; vacuumizing for 30 min. 4) And (3) plug pressing: and then, performing a pressure rise test (the pressure rise rate is less than or equal to 0.02mbar/min), and filling nitrogen and pressing the plug after the pressure rise rate is qualified.
Comparative example 1
The nitrogen-doping step (i.e., air doping) in the first drying and desolventizing drying process of example 1 was eliminated, and the other steps and conditions were the same as those of example 1.
Comparative examples 2 to 6
Comparative examples 2 to 6 are different from example 1 in the temperature rising procedure and the holding time in the first drying and the desorption drying, and other conditions and parameters, and the product formulation are the same as those in example 1.
For example, table 2 below:
TABLE 2 comparative examples 2-6 are compared to the first drying step and the resolution drying step of example 1
Test example 1 comparison of stability of Nitrogen-doped and air-doped products
The pantoprazole sodium products for injection in the two different freeze-drying processes of example 1 and comparative example 1 are placed at 40 ℃ and 75% humidity for 6 months, the characters, the clarity and the color of the solution, the related substances and the content are detected, the stability of the products is examined by comparing the data of 0 days, and the stability of the two products is compared, and the results are shown in the table 3.
Table 3 comparison of product stability results for example 1 (batch 1) and comparative example 1
Wherein, the specific names of the impurities are shown in the following table 4:
table 4:
the experimental result shows that the content of the air-doped product is reduced from 96.3% to 92.6% after the two products are subjected to an accelerated test for 6 months, and the content requirement of the product is not met. Thus, the nitrogen is added in the freeze-drying process to stabilize the product quality.
Experimental example 2 Effect of different lyophilization techniques on product quality
TABLE 5 comparison of the properties of the lyophilized products, the clarity of the redissolved solutions and the color stability
TABLE 6 comparison of the Water content of the lyophilized products prepared and the content of the related substances
The above results show that the lyophilized product prepared in example 1 can maintain a white powder state in terms of properties after being maintained at 40 ℃ for 30 days, and the solution is clear and has no discoloration after redissolving, compared with the lyophilized products in comparative examples 2 to 6; and the lyophilized formulation has a relatively low water content and a low impurity content.
Test example 3 comparison of different treatment results on the lyophilization time
TABLE 7 comparison of lyophilization times
| Examples/comparative examples | Preparation time |
| Example 1 (batch 2) | 23.3h |
| Comparative example 6 | 37.7h |
Therefore, the water of the freeze-dried product is removed by long-time desorption drying, but in the example 1, a step is added in the desorption process, the limit vacuum pumping is adopted, and then nitrogen is doped, so that the drying speed of the freeze-dried sample is increased, the water of the sample is quickly volatilized, and the freeze-drying time is shortened. The temperature programming step of comparative example 6 required 37.7 hours, approximately 27 hours after optimization, and 10 hours less than the previous process after lyophilization optimization.
Test example 4 comparison of insoluble particles after reconstitution of lyophilized product
TABLE 8 soluble particle comparison after reconstitution
The lyophilized product prepared in example 1 showed a significant reduction in insoluble particles after reconstitution compared to the reference formulation.
Test example 5 safety test for injection of pantoprazole sodium product prepared in example 1
1) In the preparation of the product in the embodiment 1, the bacterial endotoxin of the pantoprazole sodium raw material, the auxiliary material and the inner packaging material is strictly controlled, so that the bacterial endotoxin control requirement of the preparation is met, and the quality of the product is ensured. The bacterial endotoxin limits of the raw and auxiliary materials are shown in Table 9.
TABLE 9 raw and auxiliary materials, packaging material microorganisms and bacterial endotoxin limits
The bacterial endotoxin of the raw and auxiliary materials and the packaging material is controlled, and the amount of the endotoxin in each 1mg of pantoprazole is less than 1.2EU, so that the pantoprazole sodium injection medicine prepared by the method meets the quality requirement.
2) Pantoprazole sodium safety test for injection
TABLE 10 results of local tolerance test
While specific embodiments of the invention have been described above, it will be appreciated by those skilled in the art that this is by way of example only, and that the scope of the invention is defined by the appended claims. Various changes and modifications to these embodiments may be made by those skilled in the art without departing from the spirit and scope of the invention, and these changes and modifications are within the scope of the invention.
Claims (10)
1. A preparation method of a pantoprazole sodium freeze-dried preparation is characterized by comprising the following steps: uniformly mixing pantoprazole sodium with auxiliary materials, and freeze-drying; the lyophilization comprises the following steps:
1) pre-freezing: reducing the temperature to-40-45 ℃, and keeping the temperature for 2.5-3.5h to obtain a pre-frozen product;
2) primary drying: vacuumizing the pre-frozen product, adding nitrogen, heating to-11 to-13 ℃, keeping the temperature for 40-60min, and keeping for 9-11 h; heating to-4-6 deg.C for 50-70min for 3-5 h; heating to-2 ℃ at the speed of 1.0-1.5 ℃/min, and preserving heat for 1-2 h;
3) and (3) resolving and drying: raising the temperature to 9-11 ℃ at the speed of 0.9-1.1 ℃/min, and keeping the temperature for 2-4 h; heating to 28-32 deg.C for 10-20min, and maintaining for 1-3 hr; vacuumizing to limit vacuum, and keeping the temperature for 0.4-0.8 h.
2. Preparation process according to claim 1, characterized in that said pantoprazole sodium is pantoprazole sodium sesquihydrate, of formula C16H14F2N3NaO4S·1.5H2O；
And/or the auxiliary materials comprise a stabilizer, a pH regulator and water;
preferably, the stabilizer is edetate disodium for injection;
preferably, the pH regulator is sodium hydroxide;
preferably, the water is water for injection.
3. The method for preparing according to claim 2, wherein the operation of uniformly mixing comprises the steps of:
adjusting the temperature of the water for injection to be below 30 ℃, introducing nitrogen, sequentially adding the edetate disodium, the sodium hydroxide and the pantoprazole sodium sesquihydrate, and supplementing the rest water;
preferably, the operation of mixing uniformly comprises the following steps: adding the injection water according to 95% of the injection water in the formula amount, cooling the injection water to below 30 ℃, filling nitrogen, weighing the edetate disodium according to the formula amount into a preparation tank, and circularly stirring for at least 5min until the edetate disodium is completely dissolved; adding a part of the sodium hydroxide solution, and circularly stirring for at least 5min until the sodium hydroxide solution is completely dissolved; adding the pantoprazole sodium sesquihydrate according to the prescription amount, and circularly stirring for at least 20min until the pantoprazole sodium sesquihydrate is completely dissolved; adding the water for injection to full volume, and circularly stirring for at least 20min until the mixture is uniformly mixed; adjusting the pH value of the liquid medicine to 10.0-11.5 by using the other part of the sodium hydroxide solution; the sum of the dosage of the sodium hydroxide solution added twice is equal to the amount of the prescription;
and/or, after the even mixing and before the freeze-drying, the operation of filtering and canning is preferably carried out; the filtration apparatus is preferably a 0.22 μm microfiltration membrane filter.
4. The method of claim 1, wherein the pre-freezing step comprises: the temperature was reduced to-45 ℃ and held for 3 h.
5. The method according to claim 1, wherein the nitrogen gas is introduced at a pressure of 0.2 mbar.
6. The method according to claim 1, wherein the first drying step is: vacuumizing the pre-frozen product, adding nitrogen, heating to-12 ℃ under the condition that the pressure is 0.2mbar, heating for 50min, and keeping for 10 h; keeping the vacuum pressure unchanged, heating to-5 ℃, and keeping the temperature for 4 hours, wherein the heating time is 60 min; heating to 0 ℃ at the speed of 1 ℃/min, and preserving heat for 2 h.
7. The method according to claim 1, wherein the desorption drying is: heating to 10 ℃ at the speed of 1 ℃/min, and keeping the temperature for 3 h; heating to 30 deg.C for 10-20min, and maintaining for 2 hr; vacuumizing at 30 ℃, and keeping the temperature for 0.5 h;
preferably, the pressure of the ultimate vacuum is 0-0.1 MPa;
preferably, the method also comprises the step of conducting pressure rise test after the analysis drying, and when the pressure rise rate is less than or equal to 0.02mbar/min, conducting pressure plug under the condition of filling nitrogen.
8. A freeze-dried pantoprazole sodium preparation prepared by the preparation method of the freeze-dried pantoprazole sodium preparation of any one of claims 1 to 7.
9. An injection of pantoprazole sodium obtained by re-dissolving the freeze-dried pantoprazole sodium preparation of claim 8.
10. The pantoprazole sodium injection of claim 9, wherein the vehicle used for reconstitution is water.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115444826A (en) * | 2022-10-14 | 2022-12-09 | 海南锦瑞制药有限公司 | Preparation method of pantoprazole sodium for injection |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1476335A (en) * | 2000-11-22 | 2004-02-18 | ��̹��ҽҩ��˾ | Freeze-dried pantoprazole preparation and pantoprazole injection |
| CN101229138A (en) * | 2008-01-18 | 2008-07-30 | 山东罗欣药业股份有限公司 | Pantoprazole sodium freeze-dried powder injection and preparing method thereof |
-
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- 2020-06-30 CN CN202010619283.3A patent/CN111643460A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1476335A (en) * | 2000-11-22 | 2004-02-18 | ��̹��ҽҩ��˾ | Freeze-dried pantoprazole preparation and pantoprazole injection |
| CN101229138A (en) * | 2008-01-18 | 2008-07-30 | 山东罗欣药业股份有限公司 | Pantoprazole sodium freeze-dried powder injection and preparing method thereof |
Non-Patent Citations (2)
| Title |
|---|
| 姚静等主编: "《药物冻干制剂技术的设计及应用》", 30 June 2007, 中国医药科技出版社 * |
| 张强主编: "《药剂学》", 31 January 2005 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115444826A (en) * | 2022-10-14 | 2022-12-09 | 海南锦瑞制药有限公司 | Preparation method of pantoprazole sodium for injection |
| CN115444826B (en) * | 2022-10-14 | 2023-07-21 | 海南锦瑞制药有限公司 | Preparation method of pantoprazole sodium for injection |
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Application publication date: 20200911 |