CN108992427A - A kind of preparation method of Flurbiprofen sustained release preparation - Google Patents
A kind of preparation method of Flurbiprofen sustained release preparation Download PDFInfo
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- CN108992427A CN108992427A CN201711109875.5A CN201711109875A CN108992427A CN 108992427 A CN108992427 A CN 108992427A CN 201711109875 A CN201711109875 A CN 201711109875A CN 108992427 A CN108992427 A CN 108992427A
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- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
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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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5015—Organic compounds, e.g. fats, sugars
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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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide)
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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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
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- Engineering & Computer Science (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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Abstract
The present invention provides a kind of preparation method of Flurbiprofen sustained release preparation, the steps include: to be dissolved in Flurbiprofen in 95% ethyl alcohol, obtains solution A, hydroxypropylβ-cyclodextrin is added in solution A and mannitol obtains solution B;Polylactic acid and polyethylene glycol 200 are dissolved in acetone and obtain solution C, solution B and solution C are mixed into obtain solution D, solution D is transferred in magnetic stirring apparatus, continuous stirring solution D12 hours, solution D temperature is down to 0 DEG C~1 DEG C in 2 hours again and stands 12 hours, maintains solution D temperature at 0 DEG C~1 DEG C during standing.Solution D is heated after standing 12 hours, is continuously stirred when solution D temperature rises to 15 DEG C~18 DEG C, solution D temperature is controlled at 15 DEG C~18 DEG C when stirring, obtains Flurbiprofen sustained release preparation with low temperature spray drying legal system after continuously stirring 12 hours.Capsule material dosage of the present invention is moderate, and dry materials temperature is low, and obtained carrying medicine is uniform in size, and drug release is stablized, and has the characteristics that sustained release.
Description
Technical field:
The present invention relates to a kind of pharmaceutical preparation of medicine-carrying polymer preparation more particularly to a kind of Flurbiprofen sustained release preparations
Preparation method.
Background technique:
Hydroxypropylβ-cyclodextrin is a kind of ideal injection solubilizer and drug excipient in medical industry.It can be with
The water solubility of insoluble drug is improved, increases medicine stability, improve drug bioavailability, the curative effect of medicament is made to increase or take
Dosage is reduced, and adjustable or control drug rate of release reduces poisonous side effect of medicine.Can be used for oral drugs, injection,
Mucoadhesive delivery system (including schneiderian membrane, rectum, cornea etc.), Transdermal absorption drug delivery system, lipophilicity targeted drug carrier.
Polylactic acid has tight security to human body, has good biocompatibility and biodegradability, is widely used
In medicament slow release.Currently, the preparation method of polylactic acid drug bearing microsphere mainly has phase separation method, emulsion-solvent evaporation method, spray-on process
Deng.
Flurbiprofen is propionic non-steroid anti-inflammatory drugs, main by inhibiting prostaglandin synthetase to work, and is had
Analgesic, anti-inflammatory and refrigeration function.Flurbiprofen anti-inflammatory effect and analgesic activity are respectively 250 times and 50 times of aspirin, than
Brufen is strong, and toxicity is lower, is that strongest one kind is acted in the propionic non-steroid antiphlogistic being currently known.It is clinically used for pre-
Occur after anti-ophthalmologic operation extracting lens without the mottled oedema of lens caples sample, treatment cataract and rheumatic arthritis.Fluorine compares Lip river
Constant slow release at a predetermined rate after the administration of fragrant oral slow-releasing preparation, can rapid delivery of pharmaceuticals rather than conventional formulation.With
Corresponding ordinary preparation, such as fast-release tablet, capsule, oral solution are compared, and the compliance of patient can be improved and increase curative effect of medication.It is slow
The major advantage of release formulation is the blood concentration peak valley phenomenon that can be reduced dosage frequency and avoid taking ordinary preparation appearance.
Sustained release preparation can keep blood concentration to stablize within the scope of effective blood drug concentration within the relatively long time, to improve medicine
The safety of object.Flurbiprofen sustained release preparation mainly uses skeleton agent technology to produce at present, commonly uses ethyl cellulose, acrylic acid tree
Rouge, lactose, the auxiliary materials such as microcrystalline cellulose.But drug release changes during there is burst release and storage with the dosage form that such technology produces
Risk, and supplementary product consumption is big, is unfavorable for taking orally.A kind of safe and effective, reliable in quality, production efficiency are provided to this for clinic
Height, supplementary product consumption is moderate, and the stable Flurbiprofen sustained release preparation of drug release is necessary, in consideration of it, proposing the present invention.
Summary of the invention:
The technical problem to be solved by the present invention lies in overcoming the defects of the prior art, provides a kind of safe and effective, quality
Reliably, high production efficiency, supplementary product consumption is moderate, the stable Flurbiprofen sustained release preparation and preparation method thereof of drug release.
The technical problems to be solved by the invention are realized using following technical scheme.
A kind of Flurbiprofen sustained release preparation, which is characterized in that the sustained release preparation by Flurbiprofen, hydroxypropylβ-cyclodextrin,
Polylactic acid, mannitol, polyethylene glycol 200,95% ethyl alcohol and acetone composition.The Flurbiprofen sustained release preparation each component is by weight
Amount contains 95% ethyl alcohol 140~160 than comprising flurbiprofen 100, contains hydroxypropylβ-cyclodextrin 140~160, contains mannitol 30~50,
Containing acetone 180~200, contain polylactic acid 180~200, contain polyethylene glycol 200 30~50, the polylactic acid relative molecular weight is
5000~20000.
It is a further object to provide a kind of methods for being prepared into Flurbiprofen sustained release preparation, which is characterized in that
The specific steps of this method are as follows:
1) Flurbiprofen is dissolved in 95% ethyl alcohol, obtains Flurbiprofen solution, is denoted as solution A;
2) hydroxypropylβ-cyclodextrin and mannitol are added in solution A, obtains solution B;
3) polylactic acid and polyethylene glycol are dissolved in acetone, obtain polylactic acid and polyethylene glycol 200 solution, is denoted as solution C;
4) solution B and solution C are mixed, obtains solution D;
5) solution D is transferred in magnetic stirring apparatus, controls the temperature of solution D at 15 DEG C~18 DEG C, continuous stirring solution
D12 hours, then solution D temperature is down to 0 DEG C~1 DEG C in 2 hours and stands 12 hours, solution D temperature is maintained during standing
At 0 DEG C~1 DEG C;
6) solution D for obtaining step 5 heats, and continuously stirs when solution D temperature rises to 15 DEG C~18 DEG C 12 hours,
The control of solution D temperature is at 15 DEG C~18 DEG C when stirring;
7) solution D that step 6 obtains is obtained into Flurbiprofen sustained release preparation with low temperature spray drying legal system.
Flurbiprofen sustained release preparation of the invention is passed through to be released with the cumulative in vitro of commercially available same dosage form Flurbiprofen sustained release preparation
Dose comparative study, it was demonstrated that Flurbiprofen sustained release preparation drug release of the invention is more stable, and slow-release function is more preferable.And it is prepared
Method high production efficiency, capsule material dosage is moderate, and dry materials temperature is low, and obtained carrying medicine is uniform in size, and encapsulation rate is greater than
80%, drugloading rate is greater than 50%.
Detailed description of the invention
Curve a is the extracorporeal accumulating released medicine curve of 1 gained preparation of the embodiment of the present invention in Fig. 1, and curve b is commercially available identical
The extracorporeal accumulating released medicine curve of dosage form Flurbiprofen sustained release preparation.In Fig. 1, abscissa is time (hour), and ordinate is
Cumulative release amount (%).
Curve a is the extracorporeal accumulating released medicine curve of 2 gained preparation of the embodiment of the present invention in Fig. 2, and curve b is commercially available identical
The extracorporeal accumulating released medicine curve of dosage form Flurbiprofen sustained release preparation.In Fig. 2, abscissa is time (hour), and ordinate is
Cumulative release amount (%).
Curve a is the extracorporeal accumulating released medicine curve of 3 gained preparation of the embodiment of the present invention in Fig. 3, and curve b is commercially available identical
The extracorporeal accumulating released medicine curve of dosage form Flurbiprofen sustained release preparation.In Fig. 3, abscissa is time (hour), and ordinate is
Cumulative release amount (%).
Specific embodiment:
In order to be easy to understand the technical means, the creative features, the aims and the efficiencies achieved by the present invention, tie below
Specific embodiment is closed, the present invention is further explained.
For the consistency of guarantee test result, the embodiment of the present invention has used the raw material of same batch, auxiliary material, and uses
Consistent production technology prepares Flurbiprofen sustained release preparation.
Embodiment one:
1) 100g Flurbiprofen is dissolved in 140g95% ethyl alcohol, obtains Flurbiprofen ethanol solution, is denoted as solution A;
2) 140g hydroxypropylβ-cyclodextrin and 20g mannitol are added in solution A, obtains solution B;
3) 180g polylactic acid and 30g polyethylene glycol 200 are dissolved in 180g acetone, obtain polylactic acid and polyethylene glycol 200 is molten
Liquid is denoted as solution C;
4) solution B and solution C are mixed, obtains solution D;
5) solution D is transferred in magnetic stirring apparatus, controls the temperature of solution D at 15 DEG C~18 DEG C, continuous stirring solution
D12 hours, then solution D temperature is down to 0 DEG C~1 DEG C in 2 hours and stands 12 hours, solution D temperature is maintained during standing
At 0 DEG C~1 DEG C;
6) solution D for obtaining step 5 heats, and continuously stirs when solution D temperature rises to 15 DEG C~18 DEG C 12 hours,
The control of solution D temperature is at 15 DEG C~18 DEG C when stirring;
7) solution D that step 6 obtains is obtained into Flurbiprofen sustained release preparation, the temperature of spray drying with low temperature spray drying legal system
Degree control is at 55 DEG C, nozzle diameter: 0.5mm, vacuum degree: 0.03MPA, flow: 500ml/ hours.
Sample obtained by low temperature spray drying is taken, it is 80.94% that gained sample, which measures encapsulation rate, carrying drug ratio 50.71%, body
Outer release experiment proves that this preparation energy slow release Flurbiprofen, Flurbiprofen are finally discharged up to 90% or more, sees Fig. 1.
Embodiment two:
1) 100g Flurbiprofen is dissolved in 150g95% ethyl alcohol, obtains Flurbiprofen ethanol solution, is denoted as solution A;
2) 150g hydroxypropylβ-cyclodextrin and 40g mannitol are added in solution A, obtains solution B;
3) 190g polylactic acid and 40g polyethylene glycol 200 are dissolved in 190g acetone, obtain polylactic acid and polyethylene glycol 200 is molten
Liquid is denoted as solution C;
4) solution B and solution C are mixed, obtains solution D;
5) solution D is transferred in magnetic stirring apparatus, controls the temperature of solution D at 15 DEG C~18 DEG C, continuous stirring solution
D12 hours, then solution D temperature is down to 0 DEG C~1 DEG C in 2 hours and stands 12 hours, solution D temperature is maintained during standing
At 0 DEG C~1 DEG C;
6) solution D for obtaining step 5 heats, and continuously stirs when solution D temperature rises to 15 DEG C~18 DEG C 12 hours,
The control of solution D temperature is at 15 DEG C~18 DEG C when stirring;
7) solution D that step 6 obtains is obtained into Flurbiprofen sustained release preparation, the temperature of spray drying with low temperature spray drying legal system
Degree control is at 55 DEG C, nozzle diameter: 0.75mm, vacuum degree: 0.035MPA, flow: 700ml/ hours.
Sample obtained by low temperature spray drying is taken, it is 80.62% that gained sample, which measures encapsulation rate, carrying drug ratio 50.34%, body
Outer release experiment proves that this preparation energy slow release Flurbiprofen, Flurbiprofen are finally discharged up to 90% or more, sees Fig. 2.
Embodiment three:
1) 100g Flurbiprofen is dissolved in 160g95% ethyl alcohol, obtains Flurbiprofen ethanol solution, is denoted as solution A;
2) 160g hydroxypropylβ-cyclodextrin and 50g mannitol are added in solution A, obtains solution B;
3) 200g polylactic acid and 50g polyethylene glycol 200 are dissolved in 200g acetone, obtain polylactic acid and polyethylene glycol 200 is molten
Liquid is denoted as solution C;
4) solution B and solution C are mixed, obtains solution D;
5) solution D is transferred in magnetic stirring apparatus, controls the temperature of solution D at 15 DEG C~18 DEG C, continuous stirring solution
D12 hours, then solution D temperature is down to 0 DEG C~1 DEG C in 2 hours and stands 12 hours, solution D temperature is maintained during standing
At 0 DEG C~1 DEG C;
6) solution D for obtaining step 5 heats, and continuously stirs when solution D temperature rises to 15 DEG C~18 DEG C 12 hours,
The control of solution D temperature is at 15 DEG C~18 DEG C when stirring;
7) solution D that step 6 obtains is obtained into Flurbiprofen sustained release preparation with low temperature spray drying legal system,
The temperature of spray drying is controlled at 60 DEG C, and nozzle diameter: 1mm, vacuum degree: 0.04MPA, flow: 1000ml/ is small
When.
Sample obtained by low temperature spray drying is taken, it is 81.67% that gained sample, which measures encapsulation rate, carrying drug ratio 51.37%, body
Outer release experiment proves that this preparation energy slow release Flurbiprofen, Flurbiprofen are finally discharged up to 90% or more, sees Fig. 3.
The basic principles, main features and advantages of the present invention have been shown and described above.The technology of the industry
For personnel it should be appreciated that the present invention is not limited to the above embodiments, described in the above embodiment and specification is only the present invention
Preference, be not intended to limit the invention, without departing from the spirit and scope of the present invention, the present invention also has various
Changes and improvements, these changes and improvements all fall within the protetion scope of the claimed invention.The claimed scope of the invention is by institute
Attached claims and its equivalent thereof.
Claims (5)
1. a kind of preparation method of Flurbiprofen sustained release preparation, it is characterised in that the Flurbiprofen sustained release preparation compares Lip river by fluorine
Sweet smell, hydroxypropylβ-cyclodextrin, polylactic acid, mannitol, polyethylene glycol 200,95% ethyl alcohol, acetone composition.
2. the preparation method of Flurbiprofen sustained release preparation as described in claim 1, it is characterised in that the steps include:
1) Flurbiprofen is dissolved in 95% ethyl alcohol, obtains Flurbiprofen solution, is denoted as solution A;
2) hydroxypropylβ-cyclodextrin and mannitol are added in solution A, obtains solution B;
3) polylactic acid and polyethylene glycol are dissolved in acetone, obtain polylactic acid and polyethylene glycol 200 solution, is denoted as solution C;
4) solution B and solution C are mixed, obtains solution D;
5) solution D is transferred in magnetic stirring apparatus, controls the temperature of solution D at 15 DEG C~18 DEG C, continuous stirring solution D12 is small
When, then solution D temperature is down to 0 DEG C~1 DEG C in 2 hours and stands 12 hours, maintain solution D temperature at 0 DEG C during standing
~1 DEG C;
6) solution D for obtaining step 5 heats, and continuously stirs when solution D temperature rises to 15 DEG C~18 DEG C 12 hours, stirs
When solution D temperature control at 15 DEG C~18 DEG C;
7) solution D that step 6 obtains is obtained into Flurbiprofen sustained release preparation with low temperature spray drying legal system.
3. Flurbiprofen sustained release preparation each component as claimed in claim 1 or 2 contains 95% by weight comprising flurbiprofen 100
Ethyl alcohol 140~160 contains hydroxypropylβ-cyclodextrin 140~160, contains mannitol 30~50, contains acetone 180~200, contains polylactic acid
180~200, contain polyethylene glycol 200 30~50.
4. the preparation method of Flurbiprofen sustained release preparation as claimed in claim 1 or 2, it is characterised in that opposite point of polylactic acid
Son amount is 5000~20000.
5. the preparation method of Flurbiprofen sustained release preparation as claimed in claim 3, it is characterised in that the temperature of low temperature spray drying
Degree is 55 DEG C~60 DEG C, and nozzle diameter is 0.5mm~1mm, and hothouse vacuum degree is 0.03MPA~0.04MPA, solution D flow
It is 500ml/ hours~1000ml/ hours.
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
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CN113350304A (en) * | 2021-07-15 | 2021-09-07 | 上海博悦生物科技有限公司 | Non-steroidal anti-inflammatory sustained release preparation and preparation method thereof |
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2017
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
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CN113350304A (en) * | 2021-07-15 | 2021-09-07 | 上海博悦生物科技有限公司 | Non-steroidal anti-inflammatory sustained release preparation and preparation method thereof |
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