CN103083253A - Lyophilized preparation of acetaminophen and preparation method thereof - Google Patents
Lyophilized preparation of acetaminophen and preparation method thereof Download PDFInfo
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- CN103083253A CN103083253A CN2011103466936A CN201110346693A CN103083253A CN 103083253 A CN103083253 A CN 103083253A CN 2011103466936 A CN2011103466936 A CN 2011103466936A CN 201110346693 A CN201110346693 A CN 201110346693A CN 103083253 A CN103083253 A CN 103083253A
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Abstract
The present invention relates to a lyophilized preparation of acetaminophen. The lyophilized preparation is obtained by lyophilization, including: 0.5-5% of acetaminophen, 0.5-30% of a lyophilization protectant, 0.01-5% of a chelant, 0.01-5% of a pH adjusting agent, 0.01-5% of an antioxidant and the balance being a solvent. The lyophilized preparation of acetaminophen and a preparation method thereof provided by the invention help to overcome that the lyophilized preparation is vulnerable to moisture, oxygen, pH, temperature, light and other factors in the prior art. The invention provides the lyophilized preparation of acetaminophen which is good in stability and high in safety performance.
Description
Technical field
The present invention relates to field of medicine preparations, relate in particular to the lyophilized formulations field, particularly acetaminophen lyophilized formulations and preparation method thereof.
Background technology
Acetaminophen is generally prism crystallization or white crystalline powder.Odorless, mildly bitter flavor.Can be dissolved in ethanol, acetone and hot water, be slightly soluble in water, be insoluble to petroleum ether and benzene, its saturated aqueous solution pH value 5.5-6.5.
Chemical name: N-(4-hydroxy phenyl) acetamide; Molecular formula: C8H9NO2; Molecular weight: 151.170; CAS No:103-90-2.
It is the most frequently used non-steroidal anti-inflammatory antipyretic analgesic, and refrigeration function is similar to aspirin, analgesic activity a little less than, without the antiinflammatory anti rheumatism action, be best kind in acetophenone amine medicine.Be particularly suitable for to use the patient of carboxylic acids medicine.Be used for the diseases such as flu, toothache.
In the U.S., acetaminophen is total surpass the compound recipe of 600 and single component prescription drugs and the preparation of nonprescription drugs, comprise tablet, capsule sheet (a kind of dope the oval capsule shape coating tablet that designs for anti-undesirable substance), suspension, the forms such as powder and suppository.
The paracetamol injection determined of listing is the clear liquid of colourless or almost colourless slightly thickness at present.Injection system: intramuscular injection, a 0.15g～0.25g; Preparation/specification: (1) 1ml:0.075g (2) 2ml:0.25g.
Historically, the poor and dissolubility low stopping of aqueous stability the development of intravenous form of acetaminophen.When the existing of oxygen G﹠W, acetaminophen can decompose.Along with increase or the contact light of temperature, its decomposition rate will be accelerated.The pH of solution also has tremendous influence to its stability, and this makes the suitable intravenously administrable of production get acetaminophen water solution and is faced with larger challenge.Therefore the acetaminophen intravenous formulations has to add multiple auxiliary materials to cause the unstable of acetaminophen with the oxygen in protection solution.
Acetaminophen is developed to the injection freeze-dried powder, can avoid as much as possible the factors such as moisture, oxygen, pH, temperature, illumination on the impact of acetaminophen, improve its stability, effectively reduce the generation of related substance, thus the risk when reducing injection; Also played simultaneously the purpose that extends the shelf life.Acetaminophen freeze-dried powder form with powder in production and storage and transport process exists, and can be dissolved in water before use.
Summary of the invention
The object of the present invention is to provide a kind of acetaminophen lyophilized formulations of good stability.
Another object of the present invention is to provide the preparation method of above-mentioned acetaminophen lyophilized formulations.
In order to realize the foregoing invention purpose, the present invention has adopted following technical scheme:
The acetaminophen lyophilized formulations, this lyophilized formulations is obtained through lyophilizing by following material, comprises that 0.5 ~ 5% acetaminophen, 0.5 ~ 30% freeze drying protectant, 0.01 ~ 5% chelating agen, 0.01-5% pH adjusting agent, 0.01-5% antioxidant and residue are solvent.
Described freeze drying protectant is one or more mixing in sucrose, trehalose, glycine.Add freeze drying protectant not only to play the effect of lyophilizing excipient, and can play the effect of storage protection acetaminophen drug effect after freezing dry process and lyophilizing.
Described chelating agen is disodiumedetate or citric acid.
Described PH regulator is sodium dihydrogen phosphate, sodium hydrogen phosphate or citric acid/sodium citrate.Adding the PH regulator is for pH value being controlled between 5.5 ~ 6.5, improving the stability of acetaminophen lyophilized formulations.
Described antioxidant is cysteine hydrochloride or sodium sulfite.Add antioxidant in order to reduce air, water to the Oxidation of acetaminophen, improve stability.
Described solvent is water, the tert-butyl alcohol or both mixing.
The invention also discloses the preparation method of above-mentioned acetaminophen lyophilized formulations, comprise the steps:
(1) acetaminophen that takes recipe quantity is added in the container that fills solvent dissolving and joins concentrated solution, regulates pH 5.5-6.5;
(2) join 2/3 volume according to content results, add needle-use activated carbon, stir, standing;
(3) filtration, fine straining, sample examination;
(4) add water according to content and pH fixed molten;
(5) sealing after packing, lyophilization, packing.
Acetaminophen lyophilized formulations provided by the invention and preparation method thereof, overcome in background technology the acetaminophen lyophilized formulations exist stable under, be subject to the impact of the factors such as moisture, oxygen, pH, temperature, illumination, a kind of good stability, acetaminophen lyophilized formulations that security performance is high are provided.
The specific embodiment
The present invention is described further below by specific embodiment.
Embodiment 1: prepare 100 bottles of acetaminophen lyophilized formulations, adopt following material:
Acetaminophen 0.75g
Mannitol 3g
EDTA-2Na 0.2g
Sodium sulfite 0.5g
Sodium hydrogen phosphate is appropriate
Water is to 1000ml
Make 100 bottles
Preparation process:
1, the acetaminophen that takes recipe quantity is added in the container that fills 80 ℃ of waters for injection dissolving and joins concentrated solution, regulates pH 5.5-6.5;
2, join 2/3 volume according to content results, add 0.1% needle-use activated carbon, 80 ℃ of insulated and stirred 30 minutes, standing;
3,1 μ m titanium rod coarse filtration, 0.45 μ m filter membrane fine straining;
4, sample examination;
5, add water according to content and pH fixed molten;
6, cillin bottle packing;
7, lyophilization;
8, cillin bottle sealing, packing.
The present embodiment; in preparation acetaminophen lyophilized formulations; freeze drying protectant mannitol, chelating agen EDTA-2Na and antioxidant sodium sulfite have been added; and regulate pH value 5.5 ~ 6.5 with sodium hydrogen phosphate; make the good stability of the acetaminophen lyophilizing for preparing; be not subject to the impact of the factors such as moisture, oxygen, pH, temperature, illumination, the drug effect of the medicine that effectively guarantees and the safety of use.
Embodiment 2: prepare 100 bottles of acetaminophen lyophilized formulations, adopt following material:
Acetaminophen 7.5g
Mannitol 5g
EDTA-2Na 0.5g
Sodium sulfite 0.5g
Sodium hydrogen phosphate is appropriate
The tert-butyl alcohol is to 1000ml
Make 100 bottles
Preparation method is identical with embodiment 1.
Stability below by stability experiment checking acetaminophen lyophilized formulations.
1. test: experimental technique
(1) paracetamol injection determined: the preparation paracetamol injection determined, concentration: 7.5mg/ml stores under different condition, and measures its content, pH;
(2) acetaminophen freeze-dried powder: store under different condition, the water for injection dissolving is mixed with concentration: 7.5mg/ml, measure its content, pH.
2. experimental result
Finally, the stability of acetaminophen freeze-dried powder obviously is better than paracetamol injection determined.
Claims (7)
1. acetaminophen lyophilized formulations; it is characterized in that this lyophilized formulations is obtained through lyophilizing by following material, comprise that 0.5 ~ 5% acetaminophen, 0.5 ~ 30% freeze drying protectant, 0.01 ~ 5% chelating agen, 0.01-5% pH adjusting agent, 0.01-5% antioxidant and residue are solvent.
2. acetaminophen lyophilized formulations according to claim 1, is characterized in that described freeze drying protectant is one or more mixing in sucrose, trehalose, glycine.
3. acetaminophen lyophilized formulations according to claim 1, is characterized in that described chelating agen is disodiumedetate or citric acid.
4. acetaminophen lyophilized formulations according to claim 1, is characterized in that described PH regulator is sodium dihydrogen phosphate, sodium hydrogen phosphate or citric acid/sodium citrate.
5. acetaminophen lyophilized formulations according to claim 1, is characterized in that described antioxidant is cysteine hydrochloride or sodium sulfite.
6. acetaminophen lyophilized formulations according to claim 1, is characterized in that described solvent is water, the tert-butyl alcohol or both mixing.
7. the preparation method of according to claim 1 ~ 6 any one described acetaminophen lyophilized formulations, is characterized in that comprising the steps:
(1) acetaminophen that takes recipe quantity is added in the container that fills solvent dissolving and joins concentrated solution, regulates pH 5.5-6.5;
(2) join 2/3 volume according to content results, add needle-use activated carbon, stir, standing;
(3) filtration, fine straining, sample examination;
(4) add water according to content and pH fixed molten;
(5) sealing after packing, lyophilization, packing.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201110346693.6A CN103083253B (en) | 2011-11-07 | Acetaminophen lyophilized formulations and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201110346693.6A CN103083253B (en) | 2011-11-07 | Acetaminophen lyophilized formulations and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103083253A true CN103083253A (en) | 2013-05-08 |
| CN103083253B CN103083253B (en) | 2016-12-14 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105982853A (en) * | 2015-03-17 | 2016-10-05 | 成都医学院 | Paracetamol infusion solution and preparation method and application thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1548038A (en) * | 2003-05-22 | 2004-11-24 | 孙明杰 | New acetaminophen prepn |
| CN101147731A (en) * | 2006-11-22 | 2008-03-26 | 陈旭良 | Tramadol hydrochloride and paracetamol combined injection |
| CN101366695A (en) * | 2008-10-16 | 2009-02-18 | 江苏四环生物股份有限公司 | Tylenol injection and preparation method thereof |
| WO2009047634A2 (en) * | 2007-06-18 | 2009-04-16 | Combino Pharm, S.L. | Aqueous formulations of acetaminophen for injection |
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1548038A (en) * | 2003-05-22 | 2004-11-24 | 孙明杰 | New acetaminophen prepn |
| CN101147731A (en) * | 2006-11-22 | 2008-03-26 | 陈旭良 | Tramadol hydrochloride and paracetamol combined injection |
| WO2009047634A2 (en) * | 2007-06-18 | 2009-04-16 | Combino Pharm, S.L. | Aqueous formulations of acetaminophen for injection |
| CN101366695A (en) * | 2008-10-16 | 2009-02-18 | 江苏四环生物股份有限公司 | Tylenol injection and preparation method thereof |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105982853A (en) * | 2015-03-17 | 2016-10-05 | 成都医学院 | Paracetamol infusion solution and preparation method and application thereof |
| CN105982853B (en) * | 2015-03-17 | 2019-03-29 | 成都医学院 | Big infusion of a kind of paracetamol and its preparation method and application |
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Address after: Hangzhou City, Zhejiang province Binjiang District 310052 shore road 1180 China Science and Technology Park 2 Building 4 floor West Applicant after: HANGZHOU SHARPLY PHARM R&D INSTIT. Co.,Ltd. Applicant after: HAINAN POLY PHARM. Co.,Ltd. Applicant after: ZHEJIANG POLY PHARMACEUTICAL Co.,Ltd. Address before: Hangzhou City, Zhejiang province Binjiang District 310052 shore road 1180 China Science and Technology Park 2 Building 4 floor West Applicant before: HANGZHOU SHARPLY PHARM R&D INSTIT. Co.,Ltd. Applicant before: Hainan Poly Pharm Co.,Ltd. Applicant before: ZHEJIANG POLY PHARMACEUTICAL Co.,Ltd. |
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Effective date of registration: 20230117 Address after: 571127 Guilin Ocean Economic Development Zone, Meilan District, Haikou City, Hainan Province Patentee after: HAINAN POLY PHARM. Co.,Ltd. Patentee after: ZHEJIANG POLY PHARMACEUTICAL Co.,Ltd. Address before: West side of 4/F, Building 2, Huaye Science Park, No. 1180 Bin'an Road, Binjiang District, Hangzhou, Zhejiang 310052 Patentee before: HANGZHOU SHARPLY PHARM R&D INSTIT. Co.,Ltd. Patentee before: HAINAN POLY PHARM. Co.,Ltd. Patentee before: ZHEJIANG POLY PHARMACEUTICAL Co.,Ltd. |