CN103446048A - Famotidine injection and preparation method thereof - Google Patents
Famotidine injection and preparation method thereof Download PDFInfo
- Publication number
- CN103446048A CN103446048A CN201310413949XA CN201310413949A CN103446048A CN 103446048 A CN103446048 A CN 103446048A CN 201310413949X A CN201310413949X A CN 201310413949XA CN 201310413949 A CN201310413949 A CN 201310413949A CN 103446048 A CN103446048 A CN 103446048A
- Authority
- CN
- China
- Prior art keywords
- famotidine
- injection
- preparation
- adjusting agent
- stearic acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Abstract
The invention discloses a famotidine injection and a preparation method thereof. The preparation is prepared by the following steps: dissolving famotidine into the molten liquid of 15-polyethylene glycol hydroxystearate, and mixing with an osmotic pressure regulator, a pH regulator and injection water, wherein the pH value of the injection is regulated to 6.5-7.5 by the pH regulator. According to the famotidine injection and preparation method thereof disclosed by the invention, the solubility of famotidine in a neutral environment is improved by adopting 15-polyethylene glycol hydroxystearate so as to improve the stability of active ingredients; the preparation technology is simple and is suitable for industrial mass production.
Description
Technical field
The invention belongs to the pharmaceutical preparations technology field, in particular to a kind of famotidine injection, relate in particular to a kind of famotidine injection and preparation method thereof.
Background technology
Famotidine chemistry 3-[[[2-[(diamino methylene by name)-4-thiazolyl] methyl] sulfo-]-N-sulfonamides the third amidine, be the crystalline powder of white or off-white color; Mildly bitter flavor; Meet photochromic deepening; Slightly soluble in methanol, soluble,very slightly in acetone, almost insoluble in water or chloroform, easily molten in glacial acetic acid.Its fusing point is 160～165 ℃, during melting, decomposes simultaneously.Famotidine sodium chloride injection is mainly used in treating upper gastrointestinal hemorrhage, the Zhuo-Emhorn syndrome due to peptic ulcer, acute stress ulcer and hemorrhagic gastritis; The upper gastrointestinal hemorrhage that prevention aggressive stress (various major operations, as: cerebrovascular disorders, injury of head, multiple organs failure, large-area burns etc.) causes.
Famotidine is that pKa is about 7.1 alkali compounds, solvable in water under acid condition, but stability is low, and under neutrallty condition, dissolubility is low, but good stability.At present, the famotidine injection gone on the market is as cosolvent with glacial acetic acid, directly soluble in water, sterilising conditions adopts the probability of surviving method, i.e. 115 degree sterilizing in 30 minutes, unstable because of famotidine chance high temperature, related substance reaches 5%, and can not carry out sterilizing with excessively killing method, can not guarantee the gentle product quality of product sterilized water.
CN102225050B discloses the method for the standby Famotidine sodium chloride injection of a kind of enclose legal system, adopts the inclusion agents that sulfobutyl ether-beta-schardinger dextrin-is famotidine, has added a large amount of glacial acetic acid simultaneously, is 5-7 times of weight portion of famotidine.The clathrate process complexity, adopt the kind of cyclodextrin seldom at present in injection, the untoward reaction of intravenous injection cyclodextrin is nephrotoxicity and hemolytic, and teratogenesis and carcinogenecity are arranged simultaneously, so the said preparation safety is worth worry.
CN101972248B discloses a kind of famotidine for injection, contains ASPARTIC ACID.But the aseptic assurance degree of this injection powder pin is low.
CN101716136A discloses a kind of preparation method of famotidine injection, and adjuvant is selected Aspartic Acid and disodium edetate.But the untoward reaction such as disodium edetate can cause nausea, headache, urgent micturition, blood coagulation reduction; When quiet notes are too fast, can cause asystole because of the blood calcium sharp fall.
CN100438871C discloses a kind of famotidine injection, contains amide and acidic materials.Amide is selected from nicotiamide, Pyrazinamide, carbamide etc., but, at present there are no the amide of injection stage, in sterilization process, the amide substances such as carbamide itself are degraded easily simultaneously, so the said preparation safety is worth worry.
Summary of the invention
In prior art, mostly add acidic materials to improve the famotidine dissolubility, but reduced the stability of famotidine simultaneously.The inventor considers, since famotidine is stable under neutrallty condition, if can under neutrallty condition, increase the dissolubility of famotidine, must fundamentally improve medicine stability.
Further, the present invention is surprised to find that the fused solution of 15-hydroxy stearic acid macrogol ester can dissolve famotidine, and can significantly increasing medicament dissolubility in water.More unexpectedly be, adopt 15-hydroxy stearic acid macrogol ester as solubilizing agent, not only increased the water solublity of famotidine, also improved its stability, prepared injection can tolerate 121 ℃ of high temperature sterilizes, thereby provides a kind of famotidine injection of safe and effective, reliable in quality for the patient.
Particularly, the present invention is achieved through the following technical solutions:
A kind of famotidine injection, described injection is after famotidine is dissolved in to 15-hydroxy stearic acid macrogol ester fused solution, formulated with osmotic pressure regulator, pH adjusting agent and water for injection, the pH that described pH adjusting agent is regulated described injection is 6.5-7.5.
Preferably, above-mentioned famotidine injection, wherein the weight ratio of famotidine and 15-hydroxy stearic acid macrogol ester is 1:1-10.
Further preferably, above-mentioned famotidine injection, wherein the weight ratio of famotidine and 15-hydroxy stearic acid macrogol ester is 1:2-5.
Again further preferably, above-mentioned famotidine injection, the pH that wherein said pH adjusting agent is regulated described injection is 7.0-7.5.
Famotidine injection of the present invention, the pH adjusting agent that wherein adopted is hydrochloric acid, sodium hydroxide or hydrochloric acid and sodium hydroxide.
The present invention also provides the preparation technology of above-mentioned famotidine injection, by this technique, can prepare famotidine injection safe and effective, reliable in quality.Concrete technical scheme is as follows:
A kind of preparation method of above-mentioned famotidine injection, the method comprises the steps:
(1) by 15-hydroxy stearic acid macrogol ester heating and melting, add famotidine, stir famotidine is dissolved;
(2) step (1) gained fused solution is joined in the 50-60 ℃ of water for injection that contains osmotic pressure regulator, stir, obtain settled solution, add active carbon, insulation, de-charcoal, filter;
(3) adopting pH adjusting agent to adjust medicinal liquid pH is 6.5-7.5, fill, sterilizing, packing.
Preferably, the preparation method of above-mentioned famotidine injection, the pH that wherein said pH adjusting agent is regulated described injection is 7.0-7.5.
Preferably, the preparation method of above-mentioned famotidine injection, wherein said pH adjusting agent is that hydrochloric acid is or/and sodium hydroxide.
Compared with prior art, the present invention adopts 15-hydroxy stearic acid macrogol ester to strengthen the dissolubility of famotidine under neutral environment, thereby has improved the stability of active component, and after accelerated test, related substance is substantially constant, and preparation technology is simple, be applicable to industrialized great production.
The specific embodiment
Following examples further describe preparation process of the present invention and beneficial effect, embodiment is only for the purpose of illustration, do not limit the scope of the invention, within the apparent change that those of ordinary skills make according to the present invention simultaneously and modification are also contained in the scope of the invention.
Embodiment 1 famotidine injection and preparation method thereof
Famotidine 20g
15-hydroxy stearic acid macrogol ester 20g
Water for injection adds to 2000ml
Preparation method:
(1) 15-hydroxy stearic acid macrogol ester is heated to 60 ℃, makes melting, add famotidine, be stirred to dissolve;
(2) above-mentioned fused solution is joined in the water for injection that is dissolved with 0.9% sodium chloride, stir, obtain settled solution, add active carbon, 60 ℃ of insulation 20min, de-charcoal, filter;
(3) regulating medicinal liquid pH is 6.5, fill, 121 ℃ of sterilizing 20min, packing.
Embodiment 2 famotidine injections and preparation method thereof
Famotidine 20g
15-hydroxy stearic acid macrogol ester 200g
Water for injection adds to 2000ml
Preparation method:
(1) 15-hydroxy stearic acid macrogol ester is heated to 55 ℃, makes melting, add famotidine, be stirred to dissolve;
(2) above-mentioned fused solution is joined in the water for injection that is dissolved with 0.9% sodium chloride, stir, obtain settled solution, add active carbon, 60 ℃ of insulation 30min, de-charcoal, filter;
(3) regulating medicinal liquid pH is 7.5, fill, 121 ℃ of sterilizing 20min, packing.
Embodiment 3 famotidine injections and preparation method thereof
Famotidine 20g
15-hydroxy stearic acid macrogol ester 100g
Water for injection adds to 2000ml
Preparation method:
(1) 15-hydroxy stearic acid macrogol ester is heated to 55 ℃, makes melting, add famotidine, be stirred to dissolve;
(2) above-mentioned fused solution is joined in the water for injection that is dissolved with 0.9% sodium chloride, stir, obtain settled solution, add active carbon, 60 ℃ of insulation 30min, de-charcoal, filter;
(3) regulating medicinal liquid pH is 7.0, fill, 121 ℃ of sterilizing 20min, packing.
Comparative example's 1 famotidine injection and preparation method thereof
Famotidine 20g
Tween 80 100g
Water for injection adds to 2000ml
Preparation method:
(1) Tween 80 is heated to 55 ℃, makes melting, add famotidine, stir, famotidine can not dissolve fully;
(2) above-mentioned fused solution is joined in the water for injection that is dissolved with 0.9% sodium chloride, stir, obtain suspension.
Comparative example 1 adopts Tween 80 to replace 15-hydroxy stearic acid macrogol ester, and famotidine is difficult to dissolve, and this explanation Tween 80 is bad to the famotidine solubilizing effect.
Comparative example's 2 famotidine injections and preparation method thereof
Famotidine 20g
15-hydroxy stearic acid macrogol ester 100g
Water for injection adds to 2000ml
Preparation method:
15-hydroxy stearic acid macrogol ester is joined in the water for injection that is dissolved with 0.9% sodium chloride, stir, obtain settled solution, add famotidine, stir, solution is not clarified.
Comparative example 2 first is dissolved in 15-hydroxy stearic acid macrogol ester in water for injection, then adds famotidine, famotidine to be difficult to dissolve, this explanation technogenic influence drug solubility that makes up a prescription.
The study on the stability of embodiment 4 famotidine injections
1, related substance.Get respectively famotidine injection prepared by embodiment of the present invention 1-3, make with the mobile phase dilution solution that contains famotidine 0.5mg in every lml, as need testing solution; Precision measures in right amount, by mobile phase, quantitatively dilutes and makes the solution that contains famotidine 5 μ g in every lml, solution in contrast.According to the chromatographic condition under the assay item, precision measures contrast solution 20 μ l injection liquid chromatographies, regulates detection sensitivity, makes the peak height of main constituent chromatographic peak be about 20% of full scale.Precision measures need testing solution and each 20 μ l of contrast solution, annotate respectively people's chromatograph of liquid, record to main constituent peak retention time 4 times of chromatogram, in the need testing solution chromatogram if any impurity peaks, 4 times (4.0%) each impurity peak area and that must not be greater than contrast solution main peak area.
2, assay.According to high performance liquid chromatography (appendix V D), measure.Chromatographic condition and system suitability octadecylsilane chemically bonded silica are filler; With the heptanesulfonic acid sodium solution, (get sodium heptanesulfonate 2.0g, after adding water 900ml dissolving, regulating pH value with glacial acetic acid is 3.9, adds water to 1000ml)-acetonitrile-methanol (78:19:3) is mobile phase; Detect wavelength 254nm; Number of theoretical plate calculates and is not less than 1400 by the famotidine peak, and the separating degree of famotidine and adjacent impurity peaks should meet the requirements.
Algoscopy.Precision measures famotidine injection 2ml prepared by embodiment of the present invention 1-3 respectively, puts in the 50ml measuring bottle, adds methanol 5ml, and is diluted to scale by mobile phase, shakes up, and precision measures 5ml in the 20ml measuring bottle, by mobile phase, is diluted to scale, shakes up.Precision measures 20M and annotates people's chromatograph, records chromatogram; Separately get famotidine reference substance 20mg, accurately weighed, put in the 20ml measuring bottle, add methanol and dissolve in right amount and be diluted to scale, shake up, precision measures 5ml, puts in the 50ml measuring bottle, by mobile phase, is diluted to scale, shakes up, and is measured in the same method.By external standard method, with calculated by peak area, obtain.
The related substances and assay result of table 1 famotidine injection
Known according to the result of the test of table 1, famotidine injection prepared by the present invention is after accelerating investigation, and related substance is substantially constant, and changes of contents is also less.
Claims (8)
1. a famotidine injection, it is characterized in that: described injection is after famotidine is dissolved in to 15-hydroxy stearic acid macrogol ester fused solution, formulated with osmotic pressure regulator, pH adjusting agent and water for injection, the pH that described pH adjusting agent is regulated described injection is 6.5-7.5.
2. famotidine injection according to claim 1, it is characterized in that: the weight ratio of famotidine and 15-hydroxy stearic acid macrogol ester is 1:1-10.
3. famotidine injection according to claim 2, it is characterized in that: the weight ratio of famotidine and 15-hydroxy stearic acid macrogol ester is 1:2-5.
4. according to the described famotidine injection of claim 1-3 any one, it is characterized in that: the pH that described pH adjusting agent is regulated described injection is 7.0-7.5.
5. according to the described famotidine injection of claim 1-3 any one, it is characterized in that: described pH adjusting agent is that hydrochloric acid is or/and sodium hydroxide.
6. the preparation method according to the described famotidine injection of claim 1-3 any one, is characterized in that comprising the steps:
(1) by 15-hydroxy stearic acid macrogol ester heating and melting, add famotidine, stir famotidine is dissolved;
(2) step (1) gained fused solution is joined in the 50-60 ℃ of water for injection that contains osmotic pressure regulator, stir, obtain settled solution, add active carbon, insulation, de-charcoal, filter;
(3) adopting pH adjusting agent to adjust medicinal liquid pH is 6.5-7.5, fill, sterilizing, packing.
7. the preparation method of famotidine injection according to claim 6, it is characterized in that: the pH that described pH adjusting agent is regulated described injection is 7.0-7.5.
8. the preparation method of famotidine injection according to claim 6, it is characterized in that: described pH adjusting agent is that hydrochloric acid is or/and sodium hydroxide.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310413949XA CN103446048A (en) | 2013-09-12 | 2013-09-12 | Famotidine injection and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310413949XA CN103446048A (en) | 2013-09-12 | 2013-09-12 | Famotidine injection and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN103446048A true CN103446048A (en) | 2013-12-18 |
Family
ID=49729170
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310413949XA Pending CN103446048A (en) | 2013-09-12 | 2013-09-12 | Famotidine injection and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103446048A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103877579A (en) * | 2014-03-24 | 2014-06-25 | 符耿哲 | Famotidine-containing medicinal composition and preparation thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3648531B2 (en) * | 2000-12-22 | 2005-05-18 | 山之内製薬株式会社 | Famotidine injection |
| CN101507738A (en) * | 2009-03-21 | 2009-08-19 | 山西振东泰盛制药有限公司 | Preparation method of Shu Xuening injection |
| CN102225050A (en) * | 2011-06-28 | 2011-10-26 | 回音必集团(江西)东亚制药有限公司 | Method for preparing famotidine sodium chloride injection by inclusion method and product prepared by using the same |
| CN103239684A (en) * | 2013-05-23 | 2013-08-14 | 张蕊 | Zedoary oil injection and preparation method thereof |
-
2013
- 2013-09-12 CN CN201310413949XA patent/CN103446048A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3648531B2 (en) * | 2000-12-22 | 2005-05-18 | 山之内製薬株式会社 | Famotidine injection |
| CN101507738A (en) * | 2009-03-21 | 2009-08-19 | 山西振东泰盛制药有限公司 | Preparation method of Shu Xuening injection |
| CN102225050A (en) * | 2011-06-28 | 2011-10-26 | 回音必集团(江西)东亚制药有限公司 | Method for preparing famotidine sodium chloride injection by inclusion method and product prepared by using the same |
| CN103239684A (en) * | 2013-05-23 | 2013-08-14 | 张蕊 | Zedoary oil injection and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| 斯威曼: "《马丁代尔药物大典》", 31 January 2009, article "聚乙二醇15羟硬脂酸酯", pages: 1537 * |
| 无: "法莫替丁注射液", 《中国药房》, no. 5, 31 December 1994 (1994-12-31) * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103877579A (en) * | 2014-03-24 | 2014-06-25 | 符耿哲 | Famotidine-containing medicinal composition and preparation thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102302463B (en) | Lansoprazole lyophilized powder for injection and preparation method | |
| CN106692124A (en) | Acetylcysteine pharmaceutical composition and preparation method thereof | |
| CN108992400B (en) | Pharmaceutical composition containing irinotecan hydrochloride and preparation method thereof | |
| CN102429902A (en) | Pharmaceutical composition of alanyl glutamine and compound amino acid | |
| CN103463614B (en) | A kind of Argatroban injection and preparation method thereof | |
| CN106474048A (en) | A kind of more stable desonide gel preparation of quality | |
| CN103860483A (en) | Compound glycyrrhizin lyophilized powder injection and preparation method thereof | |
| CN104840418A (en) | Fasudil hydrochloride injection composition and preparation method thereof | |
| CN102038680B (en) | Medical composition | |
| CN103446048A (en) | Famotidine injection and preparation method thereof | |
| EP3984524A1 (en) | Ornidazole injection and s-ornidazole injection | |
| CN104784113B (en) | A kind of composition containing Linezolid and preparation method thereof | |
| CN103919737B (en) | A kind of sodium rebeprazole freeze-dried injection and preparation method thereof | |
| CN104606209A (en) | Compound vitamin medicine composition for injection and preparation method of compound vitamin medicine composition | |
| CN104414968A (en) | Levofloxacin single-dose eye drops and preparation method thereof | |
| CN102600072A (en) | Tirofiban hydrochloride injecta and preparation method thereof | |
| CN110812325B (en) | Method for improving storage stability of ketorolac tromethamine injection | |
| CN1493283A (en) | Edalavon powder for ampoul injection having good stability and its preparation method | |
| CN113521244B (en) | Argatroban injection and preparation method thereof | |
| CN103565747B (en) | Esomeprazole composition and preparation method thereof | |
| CN113730344A (en) | Injectable naproxen preparation and application thereof | |
| CN103830171B (en) | A kind of Ketorolac tromethamine injection and preparation method thereof | |
| CN108938573B (en) | Neuromuscular blocker composition and preparation method and application thereof | |
| CN102895178A (en) | Strong solution-type moxifloxacin hydrochloride injection and preparation method thereof | |
| CN105395477A (en) | Docetaxel injection and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20131218 |
|
| RJ01 | Rejection of invention patent application after publication |