CN1745748A - Method for stabilizing mixed powders of potassium clavic acid in mixing, packing and transporting procedures - Google Patents
Method for stabilizing mixed powders of potassium clavic acid in mixing, packing and transporting procedures Download PDFInfo
- Publication number
- CN1745748A CN1745748A CN 200410074304 CN200410074304A CN1745748A CN 1745748 A CN1745748 A CN 1745748A CN 200410074304 CN200410074304 CN 200410074304 CN 200410074304 A CN200410074304 A CN 200410074304A CN 1745748 A CN1745748 A CN 1745748A
- Authority
- CN
- China
- Prior art keywords
- clavulanate potassium
- packing
- guard method
- amoxicillin
- potassium
- 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
A process for improving the stability of the powdered mixture of potassium clavulanate, semi-synthetic penicillin, microcrystalline cellulose and SiO2 in the procedures of mixing, packing and transport features that relative humidity for mixing and packing environments is controlled to lower than 30%, the inertial gas is used as protective gas, and the powdered mixture is packed by aluminum bottle full of inertial gas and stored at 0-8 Deg C..
Description
Technical field
The present invention relates to a kind of improve clavulanate potassium and semisynthetic penicillin and microcrystalline Cellulose, silicon dioxide mixed powder mix, the method for stability in packing and the transporting procedures.
Background technology
Clavulanate potassium is a kind of beta-lactamase inhibitor, itself have only weak antibacterial activity, but it can effectively strengthen the activity that beta-lactam antibiotic resists multiple Resistant strain.At present, the mixed powder of amoxicillin or ticarcillin and clavulanic acid is widely used in clinical.
Clavulanate potassium is extremely unstable, meet heat and meet wet very fast degraded, meeting oxygen also can blast, therefore clavulanate potassium with amoxicillin, Amoxicillin Sodium, ticarcillin sodium, microcrystalline Cellulose, must take appropriate measures when silicon dioxide mixes to improve its stability, prevent its degraded and blast.
Clavulanate potassium and amoxicillin, Amoxicillin Sodium, ticarcillin sodium, microcrystalline Cellulose, silicon dioxide hybrid technique mainly may further comprise the steps: preparation, mixed process.In order to improve the stability of mixed powder, in the production process of mixed powder, take low temperature, low humidity and anti-oxygen measure usually in the prior art.The pharmaceutical production envionmental humidity generally is controlled at 45-65%, and under this relative humidity, clavulanate potassium can very fast degraded.The packing of mixed powder and the storage Aluminum-plastic composite bags that adopt more, in order to prevent blast, adopt the good Aluminum-plastic composite bag of the splendid attire state that is evacuated more, and general vacuum reaches-when 0.09MPa is following, can influence the distribution of particles state of clavulanate potassium, in case may influence the mixing homogeneity of mixture when consequently clavulanate potassium mixes with Amoxicillin Sodium or ticarcillin sodium, cause the content of injectable powder defective.
In a word, also there is not a kind of efficient ways at present to improve the stability of clavulanate potassium mixed powder in production, packing and transporting procedures.
Summary of the invention
The technical problem to be solved in the present invention provide a kind of improve clavulanate potassium and semisynthetic penicillin and microcrystalline Cellulose, silicon dioxide mix, the protectiveness method of stability in packing and the transporting procedures.
Technical problem to be solved by this invention is achieved through the following technical solutions:
In clavulanate potassium and amoxicillin, Amoxicillin Sodium, ticarcillin sodium, microcrystalline Cellulose, silicon dioxide preparation, mixed process, the relative humidity of production environment is controlled at below 30%, and passes to inert gas shielding; Medicinal Aluminum Bottle packing is adopted in the mixed packing of product, fills with noble gas in the Aluminum Bottle.
The relative humidity of wherein said production environment is preferably 10%～27%; Described noble gas is a nitrogen, is preferably the nitrogen of purity 〉=99.5% (percent by volume).Residual oxygen value in the Aluminum Bottle is 0.5%～1.0% (percent by volume).
Clavulanate potassium that relates among the present invention and the mixed proportion of amoxicillin (weight ratio) have 1: 2,1: 4,1: 7,1: 8,1: 14 or 1: 16 (pressing active component calculates); The mixed weight ratio of clavulanate potassium and Amoxicillin Sodium has 1: 5 (pressing active component calculates); The mixed weight ratio of clavulanate potassium and ticarcillin sodium has 1: 15 or 1: 30 (pressing active component calculates); The mixed weight ratio of clavulanate potassium and microcrystalline Cellulose is 1: 1; The mixed weight ratio of clavulanate potassium and silicon dioxide is 1: 1.
Also comprise in the said method prepared mixed powder 0～8 ℃ of storage.
The present invention adopts that nitrogen protection mixes with amoxicillin, Amoxicillin Sodium, ticarcillin sodium, microcrystalline Cellulose, silicon dioxide to improve clavulanate potassium, the stability in packing and the transporting procedures; be a kind of economy, simple oxygen isolation method; adopt nitrogen protection to produce down; the degraded of clavulanate potassium can be effectively reduced, and the probability of blasting can be avoided.
The pharmaceutical production envionmental humidity generally is controlled at 45～65%, and under this relative humidity, clavulanate potassium can very fast degraded.The present invention is through contrast test repeatedly and grope, and finds that relative humidity is the suitable humidity of producing the clavulanate potassium mixed powder below 30%, and under this damp condition, the clavulanate potassium degraded is not obvious.
Further illustrate beneficial effect of the present invention by the following examples, it should be understood that these embodiment only are used for the purpose of illustration, never limit the scope of the invention.
The specific embodiment
(embodiment) utilizes that guard method of the present invention is carried out the preparation of clavulanate potassium and Amoxicillin Sodium (1: 5) mixed powder, mixed, packing and storing.
5kg Amoxicillin Sodium and 1kg clavulanate potassium are added in the blender, are under the speed of 20～30rpm at rotating speed, mix 0.5～1.0 hour, and the material that mixes is packed in the medicinal Aluminum Bottle.Filling in the medicinal Aluminum Bottle with purity is 99.8% nitrogen.Nitrogen is prepared by the air nitrogen making machine, after the hose system aseptic filtration, feed in the clean aseptic Aluminum Bottle, by the residual oxygen value in oxygen analyser (specifications and models: OX-100A: Zhejiang Nanjia Analyzer Factory, Meicheng Jiande City produces) the control Aluminum Bottle, the residual oxygen value in the control Aluminum Bottle is 0.8% (percent by volume).Packaged mixed powder is deposited at 0～8 ℃.
All under nitrogen protection, carry out in the above-mentioned whole process of production.Nitrogen is produced by air nitrogen making machine (specifications and models: FDA, Beijing flies Da Jie and separates the manufacturing of gas isolation technics company limited), and when nitrogen reached 99.5% purity, nitrogen can utilize.The purity of nitrogen is by intelligent oxygen analyser (specifications and models: YHL, 703 productions of China Aerospace Science and Technology Corporation) test automatically, automatic emptying when purity does not reach 99.5%.
In the above-mentioned whole process of production, use dehumidifying unit (specifications and models: SM-LSO-05 automatically, Jin Gang air-conditioning equipment factory, Tianjin produces) relative humidity of production environment is set the controlled humidity scope 10%～27%, when relative humidity＞27%, dehumidifying starts, when relative humidity＜10%, dehumidifying stops.
The quality condition of the mixed powder that [test example] the present invention is prepared detects
1, for test agent: the embodiment of the invention is prepared and deposit the Amoxicillin Sodium in 2 years and the mixed powder of clavulanate potassium at 0～8 ℃.
2, test method and result
According to the requirement under the internal control quality standard item of Amoxicillin Sodium and clavulanate potassium mixed powder, the test sample of depositing 2 years is checked that comprehensively check result sees the following form:
| Project | Character | pH | Moisture (%) | Content (μ g/mg) | Related substance (%) |
| For test agent | Off-white powder | 9.0 | 1.2 | Contain Amoxicillin Sodium 740 and contain clavulanate potassium 148.3 | 1.2 |
Annotate: the raw material that related substance refers to bring in process of production, intermediate, degradation product, isomer, polymer, byproduct of reaction etc.
Store the Amoxicillin Sodium in 2 years and the mixed powder of clavulanate potassium and show that through quality testing its quality meets every regulation of amoxicillin sodium and clavulanate potassium (5: 1) internal control quality standard, illustrate that the inventive method can effectively improve the stability of amoxicillin sodium and clavulanate potassium (5: 1) in production, packing and transporting procedures.
Claims (8)
1, a kind of mixed powder that improves clavulanate potassium and semisynthetic penicillin and microcrystalline Cellulose, silicon dioxide mix, the guard method of stability in packing and the transporting procedures, it is characterized in that: in the mixing of clavulanate potassium and semisynthetic penicillin, microcrystalline Cellulose, silicon dioxide, packaging process, the relative humidity of production environment is controlled at below 30%, and passes to inert gas shielding; Medicinal Aluminum Bottle packing is adopted in the packing of mixed powder and storage, fills in the Aluminum Bottle with noble gas, 0～8 ℃ of storage.
2, according to the described guard method of claim 1, it is characterized in that: the relative humidity of described production environment is controlled at 10%～27%.
3, according to the described guard method of claim 1, it is characterized in that: described noble gas is a nitrogen.
4, according to the described guard method of claim 1, it is characterized in that: the purity of described nitrogen is more than or equal to 99.5%.
5, according to the described guard method of claim 1, it is characterized in that: the residual oxygen value in the described Aluminum Bottle is 0.5%～1.0%.
6, according to the described guard method of claim 1, it is characterized in that: with the mutually blended semisynthetic penicillin of clavulanate potassium is amoxicillin, Amoxicillin Sodium or ticarcillin sodium.
7, according to the described guard method of claim 6, it is characterized in that: the part by weight mixed of active component is pressed in clavulanate potassium and amoxicillin 1: 2,1: 4,1: 7,1: 8,1: 14 or 1: 16; Clavulanate potassium mixes by 1: 5 part by weight of active component with Amoxicillin Sodium; Clavulanate potassium and ticarcillin sodium mix by the part by weight of active component 1: 15 or 1: 30.
8, according to the described guard method of claim 1, it is characterized in that: clavulanate potassium mixes with the part by weight of microcrystalline Cellulose by 1: 1; Clavulanate potassium mixes with the part by weight of silicon dioxide by 1: 1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410074304 CN1745748A (en) | 2004-09-08 | 2004-09-08 | Method for stabilizing mixed powders of potassium clavic acid in mixing, packing and transporting procedures |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410074304 CN1745748A (en) | 2004-09-08 | 2004-09-08 | Method for stabilizing mixed powders of potassium clavic acid in mixing, packing and transporting procedures |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1745748A true CN1745748A (en) | 2006-03-15 |
Family
ID=36165568
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200410074304 Pending CN1745748A (en) | 2004-09-08 | 2004-09-08 | Method for stabilizing mixed powders of potassium clavic acid in mixing, packing and transporting procedures |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1745748A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113350511A (en) * | 2021-03-01 | 2021-09-07 | 郎俊娜 | Novel sterile powder filling mixed protective gas for injection |
| CN114159432A (en) * | 2020-09-11 | 2022-03-11 | 成都倍特药业股份有限公司 | Ticarcillin sodium and potassium clavulanate pharmaceutical composition and preparation method thereof |
-
2004
- 2004-09-08 CN CN 200410074304 patent/CN1745748A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114159432A (en) * | 2020-09-11 | 2022-03-11 | 成都倍特药业股份有限公司 | Ticarcillin sodium and potassium clavulanate pharmaceutical composition and preparation method thereof |
| CN114159432B (en) * | 2020-09-11 | 2024-01-09 | 成都倍特药业股份有限公司 | Tebucillin sodium clavulanate potassium pharmaceutical composition and preparation method thereof |
| CN113350511A (en) * | 2021-03-01 | 2021-09-07 | 郎俊娜 | Novel sterile powder filling mixed protective gas for injection |
| CN113350511B (en) * | 2021-03-01 | 2024-01-02 | 郎俊娜 | Novel sterile powder filling mixed shielding gas for injection |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| WO1996029996A1 (en) | Gelatin capsule with adjusted water activity | |
| CN101606934B (en) | Bendamustine hydrochloride compound | |
| CN104260923A (en) | Racking machine with nitrogen charging device | |
| CN1745748A (en) | Method for stabilizing mixed powders of potassium clavic acid in mixing, packing and transporting procedures | |
| WO2022271600A1 (en) | Stable varenicline dosage forms | |
| CN103446075B (en) | A kind of Cefaclor Capsules and preparation method thereof | |
| CN102600081B (en) | Amoxicillin and clavulanate potassium injection and preparation method thereof | |
| CN113476406A (en) | Veterinary compound amoxicillin powder and preparation process thereof | |
| NL8303125A (en) | PHARMACEUTICAL PREPARATIONS. | |
| CN1123381C (en) | Chemical oxygen absorbent and its prepn | |
| CN104814932B (en) | A kind of frozen dried method of Calcium Folinate for injection freeze drying powder injection | |
| CN100522973C (en) | Method of raising stability of potassium clavalanate in production, packing, storage and transportation | |
| CN113350511B (en) | Novel sterile powder filling mixed shielding gas for injection | |
| CN104188914B (en) | Amoxicillin powder and its production technology | |
| EP0726088B1 (en) | Process and device for the preparation of sprayable compositions | |
| CN1804117A (en) | Solid metal-organic compound package container and application thereof | |
| CN105287599A (en) | Cefradine pharmaceutical composition | |
| EP0338670A2 (en) | Pharmaceutical Compositions | |
| CN114159432B (en) | Tebucillin sodium clavulanate potassium pharmaceutical composition and preparation method thereof | |
| CN115671068B (en) | Amoxicillin and clavulanate potassium tablet and preparation method thereof | |
| CN204250434U (en) | A kind of racking machine with nitrogen charging device | |
| ATE422170T1 (en) | METHOD FOR PRODUCING A PRESSURIZED GAS MIXTURE | |
| CN112438966B (en) | Medical quantitative inhalation aerosol | |
| CN103536578A (en) | Cefixime capsule and preparation method thereof | |
| CN103655578A (en) | Powder mixing method for cefoperazone sodium and sulbactam sodium |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C12 | Rejection of a patent application after its publication | ||
| RJ01 | Rejection of invention patent application after publication |