CN110946860A - Composition containing omeprazole sodium and preparation method thereof - Google Patents
Composition containing omeprazole sodium and preparation method thereof Download PDFInfo
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- CN110946860A CN110946860A CN201911390527.9A CN201911390527A CN110946860A CN 110946860 A CN110946860 A CN 110946860A CN 201911390527 A CN201911390527 A CN 201911390527A CN 110946860 A CN110946860 A CN 110946860A
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- 229940063517 omeprazole sodium Drugs 0.000 title claims abstract description 46
- KNVABRFVZVESIL-UHFFFAOYSA-N sodium;6-methoxy-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methylsulfinyl]-1h-benzimidazole Chemical compound [Na+].N=1C2=CC(OC)=CC=C2NC=1S(=O)CC1=NC=C(C)C(OC)=C1C KNVABRFVZVESIL-UHFFFAOYSA-N 0.000 title claims abstract description 46
- 238000002360 preparation method Methods 0.000 title claims abstract description 35
- 239000000203 mixture Substances 0.000 title claims abstract description 33
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 claims abstract description 28
- 229940124274 edetate disodium Drugs 0.000 claims abstract description 26
- 239000007788 liquid Substances 0.000 claims description 36
- 239000003814 drug Substances 0.000 claims description 26
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 19
- 239000000243 solution Substances 0.000 claims description 16
- 238000000034 method Methods 0.000 claims description 15
- 239000008215 water for injection Substances 0.000 claims description 14
- 238000011049 filling Methods 0.000 claims description 12
- 238000001914 filtration Methods 0.000 claims description 12
- 229910052757 nitrogen Inorganic materials 0.000 claims description 12
- 238000001035 drying Methods 0.000 claims description 10
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 10
- 238000003756 stirring Methods 0.000 claims description 9
- 238000004108 freeze drying Methods 0.000 claims description 8
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical group [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- 238000007710 freezing Methods 0.000 claims description 6
- 230000008014 freezing Effects 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 229940079593 drug Drugs 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000000126 substance Substances 0.000 abstract description 6
- 239000000047 product Substances 0.000 description 36
- 239000012535 impurity Substances 0.000 description 11
- 239000013067 intermediate product Substances 0.000 description 6
- SUBDBMMJDZJVOS-UHFFFAOYSA-N 5-methoxy-2-{[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl}-1H-benzimidazole Chemical compound N=1C2=CC(OC)=CC=C2NC=1S(=O)CC1=NC=C(C)C(OC)=C1C SUBDBMMJDZJVOS-UHFFFAOYSA-N 0.000 description 4
- 229960000381 omeprazole Drugs 0.000 description 4
- 230000000630 rising effect Effects 0.000 description 4
- 230000009286 beneficial effect Effects 0.000 description 3
- 238000002845 discoloration Methods 0.000 description 3
- 239000003607 modifier Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- MMJMSRMOAUITKN-UHFFFAOYSA-N 2-sulfinylbenzimidazole Chemical compound C1=CC=CC2=NC(=S=O)N=C21 MMJMSRMOAUITKN-UHFFFAOYSA-N 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- 150000001556 benzimidazoles Chemical class 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000005429 filling process Methods 0.000 description 1
- 210000001914 gastric parietal cell Anatomy 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 229940126409 proton pump inhibitor Drugs 0.000 description 1
- 239000000612 proton pump inhibitor Substances 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000001502 supplementing effect Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Dermatology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention provides a composition containing omeprazole sodium, which comprises the following components in parts by weight: 426 parts of omeprazole sodium and 15 parts of edetate disodium. The invention also provides a preparation method of the omeprazole sodium-containing composition. The composition containing the omeprazole sodium provided by the invention has good stability, the product property, the pH value, related substances, the content, the color, the moisture and the like of a solution do not have the trend of obvious increase or decrease when the composition is inspected at 30 ℃ and 65% RH for 6 months, and the stability is good.
Description
Technical Field
The invention relates to the field of pharmaceutical preparations, in particular to a freeze-dried composition containing omeprazole sodium and a preparation method thereof.
Background
Omeprazole sodium is a gastric parietal cell proton pump inhibitor, is a benzimidazole derivative, has a sulfinyl benzimidazole chemical structure, is unstable to light, heat and acid, and is sensitive to metal ions. The omeprazole sodium intermediate product for injection specified by Chinese pharmacopoeia is clarified, if developed, compared with a yellow-green No. 1 standard color solution, the omeprazole sodium intermediate product is not more concentrated, the water content of a finished product is not more than 7.0 percent, the single maximum impurity is not more than 1.0 percent, and the outstanding problem existing in the quality of the current domestic variety that all the impurities are not more than 1.5 percent is that the related substances and the water content exceed the standard.
Disclosure of Invention
The technical problem to be solved by the invention is to provide a composition containing omeprazole sodium with good stability.
The invention provides a composition containing omeprazole sodium, which is characterized by comprising the following components in parts by weight: 426 parts of omeprazole sodium (400 parts of omeprazole) and 15 parts of edetate disodium.
Further, the composition containing omeprazole sodium is in the form of a freeze-dried pharmaceutical preparation, and each ten thousand bottles of the freeze-dried pharmaceutical preparation mainly comprise the following components: 426g of omeprazole sodium (400 g of omeprazole) and 15g of edetate disodium.
The invention also provides a preparation method of the omeprazole sodium-containing composition, which comprises the following preparation steps:
s1: dissolving edetate disodium in appropriate amount of water for injection, adding water for injection into the container to 60% of the total liquid preparation amount, adding pre-dissolved edetate disodium solution into the container, and stirring;
s2: adjusting the pH value of the solution prepared in the step S1 to 10.0-12.0 by using an acid-base regulator, adding omeprazole sodium, stirring, adding water for injection to the total liquid preparation amount, and stirring;
s3: and (4) filtering, filling and freeze-drying the liquid medicine prepared in the step S2.
Further, the temperature of the water for injection added in step S1 and step S2 is 15 ℃ or lower.
Further, in step S2, the measured pH of the liquid medicine sample of the total liquid preparation amount should be 10.0-12.0, otherwise, the pH is adjusted to 10.0-12.0 by using an acid-base adjusting agent.
Further, the pH regulator is sodium hydroxide solution with the concentration of 1 mol/L.
Further, in step S3, the filtering and filling are performed while maintaining the temperature of the liquid medicine below 15 ℃.
Further, filtering and filling are carried out under the protection of nitrogen.
Further, in step S3, the pre-freezing temperature for lyophilization is set to-45 ℃ to-30 ℃, the pre-freezing time is 210min, the drying temperature is set to-10 ℃ to 10 ℃, the drying time is 600min, the temperature is gradually increased to 30 ℃ to 45 ℃, and the drying time is 390 min.
The composition containing the omeprazole sodium provided by the invention has good stability, the product property, the pH value, related substances, the content, the color, the moisture and the like of a solution do not have the trend of obvious increase or decrease when the composition is inspected at 30 ℃ and 65% RH for 6 months, and the stability is good. Wherein, nitrogen protection and low-temperature preparation process are adopted in the preparation process, thereby avoiding the oxidation and color change of the product under the high-temperature condition and improving the stability of the product. Wherein, the dosage of the edetate disodium is strictly controlled, and the impurity level of the sample added with 1.5 mg/bottle of edetate disodium is obviously lower than that of the sample added with 1.2 mg/bottle of edetate disodium, thereby showing that the addition of 1.5 mg/bottle of edetate disodium is more beneficial to the stability of a finished product, and in addition, the stability of the product is improved through the parameter adjustment of the freeze-drying process, and the quality of the product is improved to be completely superior to the requirement of quality standard and superior to domestic similar varieties.
Detailed description of the invention
Example 1
The embodiment provides a composition containing omeprazole sodium, which is characterized by comprising the following components in parts by weight: 426 parts of omeprazole sodium (400 parts of omeprazole) and 15 parts of edetate disodium.
Example 2
The present example provides a composition containing omeprazole sodium in the form of a lyophilized pharmaceutical preparation, each vial of which essentially comprises the following components: 426g of omeprazole sodium (400 g of omeprazole) and 15g of edetate disodium.
Example 3
This example provides a process for the preparation of the omeprazole sodium containing composition of example 2, which is prepared by the following steps:
s1: dissolving edetate disodium in appropriate amount of water for injection, adding water for injection into container to 60% (12000ml) of total liquid preparation amount, adding dissolved edetate disodium solution into container, and stirring;
s2: adjusting the pH value of the solution prepared in the step S1 to 10.0-12.0 by using an acid-base regulator, adding omeprazole sodium, stirring, supplementing water for injection to the total liquid preparation amount (20000ml), and stirring;
s3: and (4) filtering, filling and freeze-drying the liquid medicine prepared in the step S2.
The omeprazole sodium-containing composition for injection produced by the process has good stability, the product property, the pH value, related substances, the content, the color, the moisture and the like of the solution do not have the trend of obvious increase or decrease when the composition is inspected for 6 months at 30 ℃ and 65% RH, and the stability is good.
Example 4
Sample 1: the lyophilized pharmaceutical preparation containing omeprazole sodium prepared by the method of example 3, in which edetate disodium is contained in an amount of 1.5 mg/bottle
Sample 2: the lyophilized pharmaceutical preparation containing omeprazole sodium prepared by the method of example 3 is different from sample 1 in that each ten thousand vials of the lyophilized pharmaceutical preparation contain 12g of edetate disodium, i.e., the content of edetate disodium is 1.2 mg/vial
Disodium edetate is added as a stabilizer, the disodium edetate has no obvious influence on the stability of the intermediate product solution, but has a great influence on the stability of the finished product, and the key quality indexes of two batches of samples in 0 day are basically consistent; after the sample is placed for 1 month at 30 +/-2 ℃ and 65% +/-5% RH, compared with 0 day, the properties, the clarity and the color of the solution have no obvious change, the water and the impurities are increased, and the increasing trends of 2 batches of samples have no obvious difference; when the standing time is prolonged to 5 months, the properties, the clarity and the color of the two batches of samples are not obviously changed, the water content is increased, and the impurity growth is obvious, wherein the impurity level of the sample 1 is obviously lower than that of the sample 2, which shows that the content of 1.5 mg/bottle of edetate disodium is more beneficial to the stability of a finished product than the content of 1.2 mg/bottle of edetate disodium.
Example 5
This example provides a process for the preparation of a composition containing omeprazole sodium as described in example 2, in comparison with example 3, except that,
the temperature of the water for injection added in step S1 and step S2 were both 10 ℃.
In step S2, the measured pH of the liquid medicine sample of the total liquid preparation amount should be 10.0 to 12.0, otherwise, the pH is adjusted to 10.0 to 12.0 with an acid-base modifier.
In step S3, the filtering and filling are performed while maintaining the temperature of the liquid medicine at 10 ℃.
In the preparation process of the composition containing omeprazole sodium, the temperature of the liquid medicine is kept below 15 ℃ for filtering and filling, so that the product is prevented from oxidative discoloration under the high-temperature condition, and the stability of the product is improved.
The liquid medicine is kept at 25 ℃ and 20 ℃ for 12 hours, the color of the liquid medicine is slightly changed, and other indexes are not obviously changed; the liquid medicine is kept warm for 24 hours at the temperature of 25 ℃ and 20 ℃, the color of the liquid medicine is slightly deepened, and impurities are increased; the liquid medicine is kept at the temperature of 15 ℃ for 24 hours, and all indexes have no obvious change. Therefore, the stability of the product can be obviously improved by low-temperature preparation.
Example 6
This example provides a process for the preparation of a composition containing omeprazole sodium as described in example 2, in comparison with example 3, except that,
the temperature of the water for injection added in step S1 and step S2 were both 10 ℃.
In step S2, the measured pH of the liquid medicine sample of the total liquid preparation amount should be 10.0 to 12.0, otherwise, the pH is adjusted to 10.0 to 12.0 with an acid-base modifier.
In step S3, the temperature of the liquid medicine is maintained at 10 ℃, and filtering and filling are performed under the protection of nitrogen.
In the preparation process of the composition containing omeprazole sodium, the temperature of the liquid medicine is kept below 15 ℃, and the liquid medicine is filtered and filled under the protection of nitrogen, so that the oxidation and discoloration of the product under the high-temperature condition are avoided, and the pH value of the liquid medicine in contact with air is prevented from being reduced too fast, so that the stability of the product is improved.
The liquid medicine is filtered and filled under the protection of nitrogen, the phenomenon that the pH value is reduced too fast due to the contact of the liquid medicine and air can be avoided, the stability of the liquid medicine is ensured, and after the freeze-dried finished product is placed at 60 +/-2 ℃ for 30 days, the properties, the pH value and the clarity of the solution of the product are not obviously changed compared with the color of the product after being placed at 0 day, and the moisture and the impurities are increased; the sample which is not filtered and filled under the protection of nitrogen is inspected under the same conditions, the properties, the pH value, the clarity and the color of the product are not obviously changed, the water content is increased, the impurities are obviously increased, the increase speed of the impurities of the product which is not filled with nitrogen is higher than that of the product which is filled with nitrogen, and therefore, the stability of the product can be obviously improved through the protection of nitrogen filling in the filtering and filling processes.
Example 7
This example provides a process for the preparation of a composition containing omeprazole sodium as described in example 2, in comparison with example 3, except that,
the temperature of the water for injection added in step S1 and step S2 were both 12 ℃.
In step S2, the measured pH of the liquid medicine sample of the total liquid preparation amount should be 10.0 to 12.0, otherwise, the pH is adjusted to 10.0 to 12.0 with an acid-base modifier.
In step S3, the temperature of the liquid medicine is maintained at 12 ℃, and filtering and filling are performed under the protection of nitrogen.
In step S3, the pre-freezing temperature for lyophilization is set to-40 deg.C, the pre-freezing time is 210min, the drying temperature is set to 0 deg.C, the drying time is 600min, and the temperature is gradually increased to 40 deg.C, and the drying time is 390 min.
The pre-freezing temperature is set to be-40 ℃ to ensure that the sample is completely frozen, the primary drying temperature is 0 ℃, the drying time is 600min to ensure that the sample is completely dried at one time, the phenomenon of atrophy or collapse cannot occur, the temperature is gradually increased to 40 ℃, and the drying time is 390min to ensure that the sample is dried to the preset moisture content and does not collapse or have other appearance defects, so that the product quality is ensured and the product stability is improved.
Example 8
In the preparation process of the product, when the pH value of the intermediate product is controlled below 10.0, the liquid medicine is more easily degraded and discolored, and light yellow precipitates are separated out in the normal-temperature storage process; and when the pH value of the intermediate product is controlled to be 12.0, the related substances have an obvious rising trend in stability test of the freeze-dried finished product at 40 ℃, and the pH value of the intermediate product is 10.0-12.0 after the freeze-dried finished product is placed at 40 ℃ for 2 months and exceeds the standard specification.
Example 9
The content of the finished product (lyophilized pharmaceutical preparation containing omeprazole sodium) prepared by example 7 was 99.8%. In the process of accelerating the examination of a sample at 40 +/-2 ℃ and 75 +/-5% RH for 6 months, the product properties, the pH value, insoluble particles, the color of a solution and visible foreign matters have no obvious rising or falling tendency, and the stability is good; the content measurement values are within +/-5% of the measurement value in 0 day, and no obvious rising or falling trend exists; all the quality indexes meet the quality standard specification in the product expiration date. The test result of the related indexes has no obvious trend of rising or falling and has good stability when the test is carried out at 30 +/-2 ℃ and 65 +/-5% RH for 12 months. The stability of the product can be ensured at 30 ℃ for 12 months.
In conclusion, by adopting the composition containing omeprazole sodium and the preparation method thereof provided by the invention, nitrogen protection and low-temperature preparation processes are adopted in the preparation process, so that the product is prevented from oxidative discoloration under the high-temperature condition, and the stability of the product is improved. Wherein, the dosage of the edetate disodium is strictly controlled, and the impurity level of the sample added with 1.5 mg/bottle of edetate disodium is obviously lower than that of the sample added with 1.2 mg/bottle of edetate disodium, thereby showing that the addition of 1.5 mg/bottle of edetate disodium is more beneficial to the stability of a finished product, and in addition, the stability of the product is improved through the parameter adjustment of the freeze-drying process, and the quality of the product is improved to be completely superior to the requirement of quality standard and superior to domestic similar varieties.
The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention, and various modifications and changes may be made by those skilled in the art. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (9)
1. The composition containing omeprazole sodium is characterized by comprising the following components in parts by weight: 426 parts of omeprazole sodium and 15 parts of edetate disodium.
2. The composition containing omeprazole sodium according to claim 1, which is in the form of a lyophilized pharmaceutical preparation, wherein each vial of lyophilized pharmaceutical preparation essentially comprises the following components: 426g of omeprazole sodium and 15g of edetate disodium.
3. A process for the preparation of a composition containing omeprazole sodium according to claim 1 or 2, characterized in that it is prepared by the following steps:
s1: dissolving edetate disodium in appropriate amount of water for injection, adding water for injection into the container to 60% of the total liquid preparation amount, adding pre-dissolved edetate disodium solution into the container, and stirring;
s2: adjusting the pH value of the solution prepared in the step S1 to 10.0-12.0 by using an acid-base regulator, adding omeprazole sodium, stirring, adding water for injection to the total liquid preparation amount, and stirring;
s3: and (4) filtering, filling and freeze-drying the liquid medicine prepared in the step S2.
4. The process for preparing a composition containing omeprazole sodium according to claim 3, wherein the temperature of the water for injection added in step S1 and step S2 are both below 15 ℃.
5. The method for preparing a composition containing omeprazole sodium according to claim 3, wherein in step S2, the pH value of the liquid medicine sample of the total liquid preparation amount should be 10.0-12.0, otherwise, the pH value is adjusted to 10.0-12.0 by using an acid-base regulator.
6. A process for the preparation of a composition containing omeprazole sodium according to claim 3 or 4 or 5 wherein the pH modifying agent is sodium hydroxide solution.
7. The preparation method of a composition containing omeprazole sodium according to claim 3, wherein the filtering and filling are performed while maintaining the temperature of the drug solution below 15℃ at step S3.
8. The process for the preparation of a composition containing omeprazole sodium according to claim 3, wherein the filtration and filling are performed under nitrogen protection.
9. The preparation method of a composition containing omeprazole sodium according to claim 3, 7 or 8, wherein the pre-freezing temperature for lyophilization is set to-45 to-30 ℃ for 210min, the drying temperature is set to-10 to 10 ℃ for 600min, and the temperature is gradually increased to 30 to 45 ℃ for 390min in step S3.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN116077446A (en) * | 2022-12-16 | 2023-05-09 | 上药东英（江苏）药业有限公司 | Rabeprazole sodium freeze-dried powder injection and preparation method thereof |
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