CN105997931A - Cefixime capsules and preparation method thereof - Google Patents
Cefixime capsules and preparation method thereof Download PDFInfo
- Publication number
- CN105997931A CN105997931A CN201610570933.3A CN201610570933A CN105997931A CN 105997931 A CN105997931 A CN 105997931A CN 201610570933 A CN201610570933 A CN 201610570933A CN 105997931 A CN105997931 A CN 105997931A
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- China
- Prior art keywords
- cefixime
- ethanol
- ethylenedioxybis
- diacetate
- capsules
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- 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
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
-
- 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
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
- A61K31/542—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with heterocyclic ring systems
- A61K31/545—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine
- A61K31/546—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine containing further heterocyclic rings, e.g. cephalothin
-
- 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
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
-
- 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
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses cefixime capsules and a preparation method thereof. The cefixime capsules are prepared by well mixing a compound of cefixime of L-4-bromophenylalanine and triethylene glycol diacetate with a filling agent and a disintegrating agent; adopting a dry method for granulation. A weight ratio of cefixime, triethylene glycol diacetate and L-4-bromophenylalanine is 1:2-5:0.6-1.0. The cefixime capsules prepared by the method are high in stability and dissolution and simple in production process.
Description
Technical field
The invention belongs to pharmaceutical preparations technology field, in particular to a kind of can the head of Fast Stripping in vivo and in vitro
Spore gram oxime capsule and preparation method thereof.
Background technology
Cefixime is third generation oral cephalosporin, plays bactericidal action by the synthesis of suppression bacteria cell wall.Head
Spore gram oxime is in vitro and in vivo to gram-positive cocci such as streptococcus pneumoniae, micrococcus scarlatinae, and gram is negative
Bacillus such as hemophilus influenza, moraxelle catarrhalis, escherichia coli, proteus mirabilis, gonococcus are respectively provided with the most antibacterial
Effect；Cefixime in vitro to streptococcus pneumoniae, para-influenza Bacillus, proteus vulgaris, klebsiella pneumoniae,
Pasteurella multocida, Providian bacterium, Salmonella, Shigella, serratia marcesens, special-shaped citric acid bacteria are also
Tool antibacterial activity.Clinically cefixime for caused by sensitive organism pharyngitis, tonsillitis, acute bronchitis,
Acute episode of chronic bronchitis, otitis media, urinary tract infection, Simple gonorrhea etc..
The cefixime preparation of listing has capsule, tablet, dispersible tablet, chewable tablet, granule, dry suspension at present,
It is traditional oral administered dosage form.Document report cefixime preparation all existence and stabilities are poor, and dissolution is relatively low,
Medicine absorption in vivo and distribution are relatively slow, have impact on the problem such as treatment speed and effect of medicine.
Summary of the invention
In view of the deficiencies in the prior art, it is an object of the invention to by the prescription of dry granulation and technique are ground
Study carefully, it is provided that Cefixime Capsules that a kind of stability is strong, dissolution is fast and preparation method thereof.
In order to realize the purpose of the present invention, inventor is studied by lot of experiments, is finally obtained following technical scheme:
A kind of Cefixime Capsules, dry granule after mixing with Pulvis Talci, encapsulated shell forms, and described dry granule is
After being mixed with filler, disintegrating agent by the cefixime containing L-4-bromophenyl alanine and 2,2'-ethylenedioxybis(ethanol). diacetate complex
Obtained by dry granulation, the described cefixime containing L-4-bromophenyl alanine and 2,2'-ethylenedioxybis(ethanol). diacetate complex
In, the weight ratio of cefixime, 2,2'-ethylenedioxybis(ethanol). diacetate and L-4-bromophenyl alanine is 1:2-5:0.6-1.0.
Described Cefixime Capsules, the described cefixime containing L-4-bromophenyl alanine and 2,2'-ethylenedioxybis(ethanol). diacetate are multiple
In compound, the weight ratio of cefixime, 2,2'-ethylenedioxybis(ethanol). diacetate and L-4-bromophenyl alanine is 1:3:0.8.
Described Cefixime Capsules, described filler is selected from following one or more: calcium sulphate dihydrate, fructose,
Cereal starch.
Described Cefixime Capsules, described disintegrating agent is selected from following one or more: alginic acid, glycolic form sediment
Powder sodium.
The preparation method of described Cefixime Capsules, comprises the steps: cefixime and 2,2'-ethylenedioxybis(ethanol). diacetate
It is dissolved in ethanol, adds L-4-bromophenyl alanine, stirring；Less than 50 DEG C evaporated under reduced pressure ethanol, compound by be evaporated
Thing takes out, and crosses 80-100 mesh sieve, must contain cefixime and the 2,2'-ethylenedioxybis(ethanol). diacetate complex of L-4-bromophenyl alanine；
After cefixime containing L-4-bromophenyl alanine and 2,2'-ethylenedioxybis(ethanol). diacetate complex are mixed with filler, disintegrating agent
Encapsulated shell after dry granulation, the dry granule of gained and Pulvis Talci mixing, obtains Cefixime Capsules.
Compared with prior art, Cefixime Capsules stability prepared by the present invention is strong, content after accelerating 6 months
All change without notable with there being related substance.Meanwhile, the Cefixime Capsules that prepared by the present invention is under the conditions of room temperature (20 DEG C)
Dissolution rate be significantly higher than prior art, the dissolution of its 5min, 15min is up to 84%, 92%.It addition, this
The Cefixime Capsules agent producing process of invention is simple, shortens the production cycle, raising production efficiency, energy-and time-economizing,
Such that it is able to reduce the production cost of product, it is suitable for industrialized great production.
Accompanying drawing explanation
Fig. 1 is the cumulative leaching rate curve chart of the Cefixime Capsules of embodiment 1 preparation.
Fig. 2 is the cumulative leaching rate curve chart of the Cefixime Capsules of embodiment 2 preparation.
Fig. 3 is the cumulative leaching rate curve chart of the Cefixime Capsules of embodiment 3 preparation.
Detailed description of the invention
The foregoing of the present invention is described in further detail by form more by the following examples, but should be by this
It is interpreted as that the scope of the above-mentioned theme of the present invention is only limitted to below example, all is realized based on foregoing of the present invention
Technology belong to the scope of the present invention.
Embodiment 1
Take 200g cefixime, 1000g 2,2'-ethylenedioxybis(ethanol). diacetate is dissolved in 10L ethanol, adds 120g L-4-bromine
Phenylalanine, stirring；Less than 50 DEG C evaporated under reduced pressure ethanol, take out the complex being evaporated, pulverized 80-100 mesh
Sieve, must contain cefixime and the 2,2'-ethylenedioxybis(ethanol). diacetate complex of L-4-bromophenyl alanine；Weigh 200g containing L-4-
The cefixime of bromophenyl alanine and 2,2'-ethylenedioxybis(ethanol). diacetate complex, with 180g calcium sulphate dihydrate, 30g alginic acid
Encapsulated shell after dry granulation after mixing, the dry granule of gained and the mixing of 5g Pulvis Talci, obtains Cefixime Capsules.
Embodiment 2
Take 200g cefixime, 400g 2,2'-ethylenedioxybis(ethanol). diacetate is dissolved in 10L ethanol, adds 200g silicon dioxide,
Stirring；Less than 45 DEG C evaporated under reduced pressure ethanol, take out the complex being evaporated, pulverized 80-100 mesh sieve, and must contain L-4-
The cefixime of bromophenyl alanine and 2,2'-ethylenedioxybis(ethanol). diacetate complex；Weigh the 200g head containing L-4-bromophenyl alanine
Dry granulation after spore gram oxime and 2,2'-ethylenedioxybis(ethanol). diacetate complex, with 200g fructose, the mixing of 25g Sodium Carboxymethyl Starch,
Encapsulated shell after the dry granule of gained and the mixing of 4.0g Pulvis Talci, obtains Cefixime Capsules.
Embodiment 3
Take 200g cefixime, 800g distearoyl phosphatidylcholine is dissolved in 10L ethanol, adds 160g dioxy
SiClx, stirring；Less than 50 DEG C evaporated under reduced pressure ethanol, take out the complex being evaporated, pulverized 80-100 mesh sieve,
Cefixime and the 2,2'-ethylenedioxybis(ethanol). diacetate complex of L-4-bromophenyl alanine must be contained；Weigh 200g bromobenzene Han L-4-
After the cefixime of alanine and 2,2'-ethylenedioxybis(ethanol). diacetate complex, with 180g cereal starch, the mixing of 45g alginic acid
Encapsulated shell after dry granulation, the dry granule of gained and the mixing of 4.0g Pulvis Talci, obtains Cefixime Capsules.
The stability study of embodiment 4 Cefixime Capsules
According to by commercially available back, Cefixime Capsules sample prepared by Example 1-3, in temperature (4O ± 2) DEG C,
Place 6 months under conditions of relative humidity (75 ± 5) %.Test 1st month period, 2 months, 3 months, 6
The individual the end of month is separately sampled once, detects by stability high spot reviews project, to determine its stability.Result of the test is shown in
Table 1.By the result of the test of table 1 it can be seen that Cefixime Capsules prepared by embodiment of the present invention 1-3 is accelerating 6
Content and have related substance all without significantly changing after individual month, this has absolutely proved prepared by the prescription of the employing present invention and technique
Cefixime Capsules there is extraordinary stability.
The accelerated test result of table 1 Cefixime Capsules
The study in vitro dissolution of embodiment 5 Cefixime Capsules
According to 2005 editions two annex XC the second methods of Chinese Pharmacopoeia, with the phosphate buffer processed through degassing
(pH=6.5) 1000mL is dissolution medium, temperature 37 ± 0.5 DEG C, rotating speed 100r/min.Sample in 30min, warp
0.45 μm filtering with microporous membrane (sampling and filter operation should complete in 30s).It is appropriate that precision measures subsequent filtrate, uses
Phosphate buffer (pH=6.5) is diluted to the solution of l0 μ g/mL；Separately take cefixime reference substance appropriate, add above-mentioned
Phosphate buffer makes the solution (if desired supersound process make dissolving complete) of 10 μ g/mL.Take above two solution,
It is measured, at the wavelength of 288nm, measures trap respectively, calculate dissolution.Take the embodiment of the present invention respectively
Each 6 of sample prepared by 1-3, checks according to said method, respectively at 4,8,12,16,20,24min
Sampling and measuring.Stripping curve is shown in figure l-3.
From the result of the test of Fig. 1-3, Cefixime Capsules prepared by the present invention is under the conditions of room temperature (20 DEG C)
Dissolution rate is greatly increased, and the dissolution of its 5min, 15min is up to 84%, 92%.
Claims (5)
1. a Cefixime Capsules, dry granule after mixing with Pulvis Talci, encapsulated shell forms, it is characterised in that: institute
The dry granule stated is by the cefixime containing L-4-bromophenyl alanine and 2,2'-ethylenedioxybis(ethanol). diacetate complex and filler, disintegrate
Being obtained by dry granulation after agent mixing, the described cefixime containing L-4-bromophenyl alanine and 2,2'-ethylenedioxybis(ethanol). diacetate are multiple
In compound, the weight ratio of cefixime, 2,2'-ethylenedioxybis(ethanol). diacetate and L-4-bromophenyl alanine is 1:2-5:0.6-1.0.
Cefixime Capsules the most according to claim 1, it is characterised in that: described containing L-4-bromophenyl alanine
In cefixime and 2,2'-ethylenedioxybis(ethanol). diacetate complex, cefixime, 2,2'-ethylenedioxybis(ethanol). diacetate and L-4-bromophenyl alanine
Weight ratio is 1:3:0.8.
3. according to Cefixime Capsules according to claim 1, it is characterised in that: described filler is selected from as follows
One or more: calcium sulphate dihydrate, fructose, cereal starch.
Cefixime Capsules the most according to claim 1, it is characterised in that: described disintegrating agent is selected from following one
Plant or multiple: alginic acid, Sodium Carboxymethyl Starch.
5. the preparation method of a Cefixime Capsules according to claim 1 or claim 2, it is characterised in that include as follows
Step: cefixime and 2,2'-ethylenedioxybis(ethanol). diacetate are dissolved in ethanol, adds L-4-bromophenyl alanine, stirring；50 DEG C with
Lower evaporated under reduced pressure ethanol, takes out the complex being evaporated, crosses 80-100 mesh sieve, must contain the cephalo of L-4-bromophenyl alanine
Gram oxime and 2,2'-ethylenedioxybis(ethanol). diacetate complex；Cefixime containing L-4-bromophenyl alanine and 2,2'-ethylenedioxybis(ethanol). diacetate are combined
Dry granulation after thing and filler, disintegrating agent mixing, the dry granule of gained mix with Pulvis Talci after encapsulated shell, obtain cephalo gram
Oxime capsule.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610570933.3A CN105997931A (en) | 2016-07-19 | 2016-07-19 | Cefixime capsules and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610570933.3A CN105997931A (en) | 2016-07-19 | 2016-07-19 | Cefixime capsules and preparation method thereof |
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| Publication Number | Publication Date |
|---|---|
| CN105997931A true CN105997931A (en) | 2016-10-12 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610570933.3A Pending CN105997931A (en) | 2016-07-19 | 2016-07-19 | Cefixime capsules and preparation method thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107669644A (en) * | 2017-10-27 | 2018-02-09 | 南京多宝生物科技有限公司 | A kind of Roxithromycin Tablets and preparation method thereof |
| CN108042505A (en) * | 2018-01-02 | 2018-05-18 | 上海祺宇生物科技有限公司 | A kind of plant hollow capsule for being exclusively used in Cefixime |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5412094A (en) * | 1993-06-28 | 1995-05-02 | Eli Lilly And Company | Bicyclic beta-lactam/paraben complexes |
| CN1593423A (en) * | 2004-06-18 | 2005-03-16 | 余安国 | Cefixime pharmaceutical composition for injection |
| CN103040782A (en) * | 2013-01-24 | 2013-04-17 | 南京正宽医药科技有限公司 | Cefixime tablets and preparation method thereof |
| CN103110607A (en) * | 2013-03-01 | 2013-05-22 | 浙江华立南湖制药有限公司 | Cefixime capsule and preparation method thereof |
-
2016
- 2016-07-19 CN CN201610570933.3A patent/CN105997931A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5412094A (en) * | 1993-06-28 | 1995-05-02 | Eli Lilly And Company | Bicyclic beta-lactam/paraben complexes |
| CN1593423A (en) * | 2004-06-18 | 2005-03-16 | 余安国 | Cefixime pharmaceutical composition for injection |
| CN103040782A (en) * | 2013-01-24 | 2013-04-17 | 南京正宽医药科技有限公司 | Cefixime tablets and preparation method thereof |
| CN103110607A (en) * | 2013-03-01 | 2013-05-22 | 浙江华立南湖制药有限公司 | Cefixime capsule and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| 江波等: ""提高难溶性药物口服生物利用度的方法"", 《中国医药工业杂志》 * |
| 高建德等: "《物理药剂学及应用》", 31 May 2014 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107669644A (en) * | 2017-10-27 | 2018-02-09 | 南京多宝生物科技有限公司 | A kind of Roxithromycin Tablets and preparation method thereof |
| CN108042505A (en) * | 2018-01-02 | 2018-05-18 | 上海祺宇生物科技有限公司 | A kind of plant hollow capsule for being exclusively used in Cefixime |
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