CN113230208A - Fluconazole sodium chloride injection and preparation method thereof - Google Patents
Fluconazole sodium chloride injection and preparation method thereof Download PDFInfo
- Publication number
- CN113230208A CN113230208A CN202110465090.1A CN202110465090A CN113230208A CN 113230208 A CN113230208 A CN 113230208A CN 202110465090 A CN202110465090 A CN 202110465090A CN 113230208 A CN113230208 A CN 113230208A
- Authority
- CN
- China
- Prior art keywords
- injection
- sodium chloride
- fluconazole
- preparation
- prescription
- 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.)
- Withdrawn
Links
Classifications
-
- 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
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
- A61J3/00—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4196—1,2,4-Triazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/14—Alkali metal chlorides; Alkaline earth metal chlorides
-
- 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
Abstract
The invention relates to the technical field of medicine, in particular to a fluconazole sodium chloride injection and a preparation method thereof, wherein the injection comprises fluconazole and sodium chloride with prescription amount, the rest is water for injection, the pH value of the injection is 5.0-7.0, the preparation process comprises the steps of adding water for injection which accounts for 80-90% of the total volume of the prescription into a diluting preparation tank, sequentially adding the sodium chloride and the fluconazole with prescription amount, and stirring for dissolving; adding water for injection to the full amount of the prescription, stirring, sampling and detecting; the injection is filtered, filled, sealed, sterilized, inspected by a lamp and packaged after being checked to be qualified, the prescription of the injection does not contain a pH regulator, impurities cannot be introduced, the product is ensured to meet the specification, the quality is stable, the preparation process is carried out by adopting a dilute preparation method, the preparation process is simplified, the activated carbon adsorption process is avoided, the titanium rod filtering process is removed, the post-treatment process using activated carbon and a titanium rod is avoided, the process can be simplified, the production cost is reduced and the environment is protected while the product quality is ensured to be stable.
Description
Technical Field
The invention relates to the technical field of medicines, and particularly relates to a fluconazole sodium chloride injection and a preparation method thereof.
Background
The existing fluconazole sodium chloride injection usually contains a pH regulator, impurities can be introduced by adding the pH regulator, certain influence is caused on the quality of the injection, meanwhile, in the preparation process, concentrated preparation is usually carried out firstly, diluted preparation is carried out after filtration, activated carbon is required to be used for adsorption in the concentrated preparation process, and finally the titanium rod is used for filtration.
Disclosure of Invention
The invention aims to provide a fluconazole sodium chloride injection, which solves the technical problem that the product quality is influenced because impurities are introduced due to the addition of a pH regulator in the existing fluconazole sodium chloride injection.
The invention is realized by the following technical scheme: the injection comprises the fluconazole, sodium chloride and the balance of water for injection according to the prescription amount, and the pH value of the injection is 5.0-7.0.
Preferably, the weight ratio of fluconazole to sodium chloride in the injection is 2:9, and both the fluconazole and the sodium chloride are pure.
The invention also aims to provide a preparation method of the fluconazole sodium chloride injection, which solves the technical problems that the existing fluconazole sodium chloride injection has complicated process in the preparation process, and the activated carbon and the titanium rod are used during concentration to increase the production cost and influence the product quality.
The invention is realized by the following technical scheme: the method comprises the following steps:
(1) adding water for injection accounting for 80-90% of the total volume of the prescription into a diluting preparation tank, sequentially adding sodium chloride and fluconazole according to the prescription amount, and stirring for dissolving;
(2) adding water for injection to the full amount of the prescription, stirring for 5-10 min, sampling and detecting the pH value, the content of fluconazole and sodium chloride and visible foreign matters;
(3) and after the inspection is qualified, filtering, filling, sealing, sterilizing, inspecting by a lamp, and packaging.
Preferably, the volume of the water for injection filled in the step (1) accounts for 85% of the total prescription.
Preferably, the filtration in the step (3) is three-stage filtration, the first stage of filtration adopts a polypropylene filter element, and the second stage of filtration and the third stage of filtration both adopt polyether sulfone filter elements.
Preferably, the aperture of the polypropylene filter element is 0.45 μm, the apertures of the second-stage and third-stage polyethersulfone filter elements are both 0.22 μm, the first-stage filtration uses one polypropylene filter element, and the second-stage and third-stage filtration both use one polyethersulfone filter element.
Preferably, the temperature of the injection during the three-stage filtration is 35-50 ℃.
Preferably, the temperature of the water for injection in the step (1) is 40-80 ℃.
Preferably, the sterilization condition in the step (1) is sterilization at 121 ℃ for 12 min.
Compared with the prior art, the invention has the following advantages and beneficial effects:
(1) the prescription of the fluconazole sodium chloride injection does not contain a pH regulator, so that the pH can reach the standard specification without adding the pH regulator, impurities can not be introduced, the product quality is ensured, the product quality is more stable, and the clinical use effect is better.
(2) The product of the invention adopts a dilute preparation method in the preparation process, replaces the existing preparation process of converting concentrated preparation into dilute preparation, simplifies the preparation process, has no activated carbon adsorption process, does not need to treat activated carbon, reduces the production cost and does not pollute the environment.
(3) In the prior preparation process, the filter element is required to be used for multi-stage filtration after the titanium rod is adopted for filtration, and the number of the filter elements used for each stage of filtration is more.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail below with reference to examples, and the exemplary embodiments and descriptions thereof are only used for explaining the present invention and are not used as limitations of the present invention.
The invention relates to a fluconazole sodium chloride injection, which comprises fluconazole, sodium chloride and water for injection in a formula amount, wherein the mass ratio of the fluconazole to the sodium chloride is 2:9, the fluconazole and the sodium chloride are pure, the pH value of the injection before sterilization is 5.4-6.6, and the pH value of the injection after packaging is 5.0-7.0.
Specifically, the following examples are given:
example 1:
preparing 1000ml of injection, weighing 2g of fluconazole and 9g of sodium chloride, wherein the fluconazole and the sodium chloride are pure for later use.
The preparation method comprises the following steps:
(1) adding water for injection accounting for 80% of the total volume of the prescription into a diluting preparation tank, controlling the temperature of the water for injection to be 40 ℃, sequentially adding sodium chloride and fluconazole which are weighed in advance according to the prescription amount, and stirring until the sodium chloride and the fluconazole are dissolved;
(2) adding water for injection to full dose, stirring for 5min to uniformity, sampling, and detecting the shape, pH value, fluconazole, sodium chloride content and visible foreign matter of the injection;
(3) and after the detection is qualified, controlling the temperature of the liquid medicine at 35 ℃, sequentially performing primary filtration by using a polypropylene filter element with the aperture of 0.45 mu m, secondary filtration by using a polyether sulfone filter element with the aperture of 0.22 mu m, and tertiary filtration by using a polyether sulfone filter element with the aperture of 0.22 mu m, subpackaging the obtained product into a vertical polypropylene infusion bag, sealing the infusion bag, sterilizing the obtained product at 121 ℃ for 12min, and performing lamp inspection and packaging.
Example 2:
preparing 1000ml of injection, weighing 2g of fluconazole and 9g of sodium chloride, wherein the fluconazole and the sodium chloride are pure for later use.
The preparation method comprises the following steps:
(1) adding water for injection which accounts for 90% of the total volume of the prescription into a diluting preparation tank, controlling the temperature of the water for injection to be 80 ℃, sequentially adding sodium chloride and fluconazole which are weighed in advance according to the prescription amount, and stirring until the sodium chloride and the fluconazole are dissolved;
(2) adding water for injection to full dose, stirring for 10min to uniformity, sampling, and detecting the shape, pH value, fluconazole, sodium chloride content and visible foreign matter of the injection;
(3) and after the detection is qualified, controlling the temperature of the liquid medicine at 50 ℃, sequentially performing primary filtration by using a polypropylene filter element with the aperture of 0.45 mu m, secondary filtration by using a polyether sulfone filter element with the aperture of 0.22 mu m and tertiary filtration by using a polyether sulfone filter element with the aperture of 0.22 mu m, subpackaging the obtained product into a vertical polypropylene infusion bag, sealing the infusion bag, sterilizing the obtained product at 121 ℃ for 12min, and performing lamp inspection and packaging.
Example 3:
preparing 1000ml of injection, weighing 2g of fluconazole and 9g of sodium chloride, wherein the fluconazole and the sodium chloride are pure for later use.
The preparation method comprises the following steps:
(1) adding water for injection accounting for 85% of the total volume of the prescription into a diluting preparation tank, controlling the temperature of the water for injection to be 60 ℃, sequentially adding sodium chloride and fluconazole which are weighed in advance according to the prescription amount, and stirring until the sodium chloride and the fluconazole are dissolved;
(2) adding water for injection to full dose, stirring for 8min to uniformity, sampling, and detecting the shape, pH value, fluconazole, sodium chloride content and visible foreign matter of the injection;
(3) and after the detection is qualified, controlling the temperature of the liquid medicine at 45 ℃, sequentially performing primary filtration by using a polypropylene filter element with the aperture of 0.45 mu m, secondary filtration by using a polyether sulfone filter element with the aperture of 0.22 mu m and tertiary filtration by using a polyether sulfone filter element with the aperture of 0.22 mu m, subpackaging the obtained product into a vertical polypropylene infusion bag, sealing the infusion bag, sterilizing the obtained product at 121 ℃ for 12min, and performing lamp inspection and packaging.
The stability test of the fluconazole sodium chloride injection is researched, and the test process and the result are as follows:
according to the requirements of 9001 raw material medicaments and preparation stability test guiding principles of the general rules of the four ministry of the version 2015 in Chinese pharmacopoeia, the product of the invention is taken according to the inner packaging conditions of the product on the market: the method comprises the following steps of storing the vertical polypropylene infusion bag in a closed manner, placing the vertical polypropylene infusion bag into a constant-temperature and constant-humidity box, carrying out an accelerated test under the conditions that the temperature is 40 +/-2 ℃ and the relative humidity is not more than 25%, sampling in 0, 1, 2, 3 and 6 months respectively, carrying out important items of investigation according to stability, investigating properties, pH values, contents of fluconazole and sodium chloride, related substances, insoluble particles, visible foreign matters and other items of the sample, increasing the items of bacterial endotoxin and bacteria free of the investigation sample at the time of the test ending point, and comparing with the investigation data result of 0 month, wherein the table I shows that:
watch 1
According to the data shown in the table, after the product is stored for 1, 2, 3 and 6 months through an accelerated experiment, the product has the characteristics that the product meets the specification, the pH value is very stable, the contents of fluconazole, sodium chloride and related substances are also very stable, the contents are all in the range specified by the standard, insoluble particles and visible foreign matters are not detected, bacterial endotoxin and sterile items also meet the specification of the standard, and the quality of the product is very stable.
The above-mentioned embodiments are intended to illustrate the objects, technical solutions and advantages of the present invention in further detail, and it should be understood that the above-mentioned embodiments are merely exemplary embodiments of the present invention, and are not intended to limit the scope of the present invention, and any modifications, equivalent substitutions, improvements and the like made within the spirit and principle of the present invention should be included in the scope of the present invention.
Claims (9)
1. A fluconazole sodium chloride injection is characterized in that: the injection comprises the fluconazole, sodium chloride and the balance of water for injection according to the prescription amount, and the pH value of the injection is 5.0-7.0.
2. The fluconazole sodium chloride injection of claim 1, wherein: the injection comprises fluconazole and sodium chloride in a weight ratio of 2:9, wherein the fluconazole and the sodium chloride are pure.
3. The preparation method of fluconazole sodium chloride injection as claimed in claim 1, which is characterized by comprising the following steps:
(1) adding water for injection accounting for 80-90% of the total volume of the prescription into a diluting preparation tank, sequentially adding sodium chloride and fluconazole according to the prescription amount, and stirring for dissolving;
(2) adding water for injection to the full amount of the prescription, stirring for 5-10 min, sampling and detecting the pH value, the content of fluconazole and sodium chloride and visible foreign matters;
(3) and after the inspection is qualified, filtering, filling, sealing, sterilizing, inspecting by a lamp, and packaging.
4. The preparation method of fluconazole sodium chloride injection as claimed in claim 3, which is characterized in that: the volume of the water for injection filled in the step (1) accounts for 85 percent of the total amount of the prescription.
5. The preparation method of fluconazole sodium chloride injection as claimed in claim 3 or 4, wherein the preparation method comprises the following steps: and (4) filtering in the step (3) is three-stage filtering, wherein the first-stage filtering adopts a polypropylene filter element for filtering, and the second-stage filtering and the third-stage filtering both adopt polyether sulfone filter elements for filtering.
6. The preparation method of fluconazole sodium chloride injection as claimed in claim 5, which is characterized in that: the aperture of the polypropylene filter element is 0.45 mu m, the aperture of the second-stage polyether sulfone filter element and the aperture of the third-stage polyether sulfone filter element are both 0.22 mu m, the polypropylene filter element is used for the first-stage filtration, and the polyether sulfone filter elements are used for the second-stage filtration and the third-stage filtration.
7. The preparation method of fluconazole sodium chloride injection as claimed in claim 6, which is characterized in that: the temperature of the injection during the three-stage filtration is 35-50 ℃.
8. The preparation method of fluconazole sodium chloride injection as claimed in claim 7, which is characterized in that: the temperature of the water for injection in the step (1) is 40-80 ℃.
9. The preparation method of fluconazole sodium chloride injection as claimed in any one of claims 6 to 8, wherein the preparation method comprises the following steps: the sterilization condition in the step (1) is sterilization for 12min at 121 ℃.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110465090.1A CN113230208A (en) | 2021-04-28 | 2021-04-28 | Fluconazole sodium chloride injection and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110465090.1A CN113230208A (en) | 2021-04-28 | 2021-04-28 | Fluconazole sodium chloride injection and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN113230208A true CN113230208A (en) | 2021-08-10 |
Family
ID=77129787
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110465090.1A Withdrawn CN113230208A (en) | 2021-04-28 | 2021-04-28 | Fluconazole sodium chloride injection and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113230208A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113181113A (en) * | 2021-04-28 | 2021-07-30 | 四川科伦药业股份有限公司 | Preparation method of metronidazole sodium chloride injection |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106902077A (en) * | 2017-03-03 | 2017-06-30 | 安徽环球药业股份有限公司 | The compound method of fluorine exchange |
| CN111266012A (en) * | 2018-12-05 | 2020-06-12 | 广州中国科学院先进技术研究所 | Continuous membrane integration device and process for medicine separation and concentration |
-
2021
- 2021-04-28 CN CN202110465090.1A patent/CN113230208A/en not_active Withdrawn
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106902077A (en) * | 2017-03-03 | 2017-06-30 | 安徽环球药业股份有限公司 | The compound method of fluorine exchange |
| CN111266012A (en) * | 2018-12-05 | 2020-06-12 | 广州中国科学院先进技术研究所 | Continuous membrane integration device and process for medicine separation and concentration |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113181113A (en) * | 2021-04-28 | 2021-07-30 | 四川科伦药业股份有限公司 | Preparation method of metronidazole sodium chloride injection |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN113230208A (en) | Fluconazole sodium chloride injection and preparation method thereof | |
| CN112842992A (en) | Dopamine hydrochloride injection serving as reference preparation and preparation method thereof | |
| CN113876697A (en) | Dopamine hydrochloride injection and preparation process thereof | |
| CN112842991B (en) | Preparation method of granisetron hydrochloride injection | |
| CN110123745A (en) | A kind of Taxol injection liquid and preparation method thereof being resistant to terminal sterilization | |
| CN102274170A (en) | Method for preparing tinidazole and sodium chloride injection | |
| CN109998990B (en) | Small-size epinephrine hydrochloride injection and preparation method thereof | |
| CN106902077A (en) | The compound method of fluorine exchange | |
| CN107496349A (en) | Filling ambroxol hydrochloride injection composition of a kind of plastic ampoule and preparation method thereof | |
| CN112957322B (en) | Levofloxacin lactate sodium chloride injection and preparation method thereof | |
| CN102018668A (en) | Preparation method of aceglutamide | |
| CN111904929B (en) | Amikacin sulfate injection and preparation method thereof | |
| CN101664385B (en) | Ibutilide fumarate injection and preparation method thereof | |
| CN104337760B (en) | A kind of Maxamine injection and preparation method thereof | |
| CN102688188B (en) | Cinepazide maleate injection and preparation method thereof | |
| CN112569184A (en) | Tirofiban hydrochloride injection and preparation method thereof | |
| CN105434343A (en) | Irinotecan hydrochloride injection and preparation method thereof | |
| CN111965314A (en) | Infant formula milk powder based chlorate and perchlorate standard sample and preparation method thereof | |
| CN111067864A (en) | Ropivacaine hydrochloride sodium chloride injection and preparation method thereof | |
| CN110613683A (en) | Fluconazole sodium chloride injection and preparation method thereof | |
| CN112999147A (en) | Stable cinepazide maleate preparation and preparation method thereof | |
| CN111632029B (en) | Methocarbamol injection and preparation method thereof | |
| CN104510702B (en) | A kind of pharmaceutical composition containing Ornidazole and its preparation | |
| CN115444816A (en) | Calcium gluconate and sodium chloride injection and preparation method thereof | |
| CN115634196B (en) | Stable-quality anisodine hydrobromide injection and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WW01 | Invention patent application withdrawn after publication |
Application publication date: 20210730 |
|
| WW01 | Invention patent application withdrawn after publication |