CN108992420A - A kind of preparation method of salbutamol sustained release preparation - Google Patents
A kind of preparation method of salbutamol sustained release preparation Download PDFInfo
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- CN108992420A CN108992420A CN201711109358.8A CN201711109358A CN108992420A CN 108992420 A CN108992420 A CN 108992420A CN 201711109358 A CN201711109358 A CN 201711109358A CN 108992420 A CN108992420 A CN 108992420A
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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
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
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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)
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- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The present invention provides a kind of preparation method of salbutamol sustained release preparation, the steps include: to be dissolved in salbutamol 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 salbutamol 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 salbutamol 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.
Salbutamol is selective β 2 receptor agonist, can effectively inhibit the release that histamine etc. causes anaphylaxis substance, is prevented
Only bronchial spasm.Suitable for diseases such as bronchial asthma, asthmatic bronchitis, bronchial spasm, pulmonary emphysema.Salbutamol mouth
Constant slow release at a predetermined rate after sustained release preparation administration is taken, it can rapid delivery of pharmaceuticals rather than conventional formulation.With it is corresponding
Ordinary preparation, such as fast-release tablet, capsule, oral solution compares, the compliance of patient can be improved and increase curative effect of medication.Sustained release system
The major advantage of agent 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 drug
Safety.Salbutamol sustained release preparation mainly uses skeleton agent technology to produce at present, common ethyl cellulose, acrylic resin,
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, high production efficiency are provided for clinic to this,
Supplementary product consumption is moderate, and the stable salbutamol 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 salbutamol 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 salbutamol sustained release preparation, which is characterized in that the sustained release preparation by salbutamol, hydroxypropylβ-cyclodextrin,
Polylactic acid, mannitol, polyethylene glycol 200,95% ethyl alcohol and acetone composition.The salbutamol sustained release preparation each component is by weight
Amount containing 95% ethyl alcohol 140~160, contains hydroxypropylβ-cyclodextrin 140~160, contains mannitol 30~50 than containing salbutamol 100,
Containing acetone 150~170, contain polylactic acid 150~170, 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 salbutamol sustained release preparation, which is characterized in that
The specific steps of this method are as follows:
1) salbutamol is dissolved in 95% ethyl alcohol, obtains albuterol solution, be 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 salbutamol sustained release preparation with low temperature spray drying legal system.
Salbutamol sustained release preparation of the invention is passed through to be released with the cumulative in vitro of commercially available same dosage form salbutamol sustained release preparation
Dose comparative study, it was demonstrated that salbutamol 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 salbutamol 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 salbutamol 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 salbutamol 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 salbutamol sustained release preparation.
Embodiment one:
1) 100g salbutamol is dissolved in 140g95% ethyl alcohol, obtains salbutamol ethanol solution, is denoted as solution A；
2) 140g hydroxypropylβ-cyclodextrin and 20g mannitol are added in solution A, obtains solution B；
3) 150g polylactic acid and 30g polyethylene glycol 200 are dissolved in 150g 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 salbutamol 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 80.23% that gained sample, which measures encapsulation rate, carrying drug ratio 50.35%, body
Outer release experiment proves that this preparation energy slow release salbutamol, salbutamol are finally discharged up to 90% or more, sees Fig. 1.
Embodiment two:
1) 100g salbutamol is dissolved in 150g95% ethyl alcohol, obtains salbutamol ethanol solution, is denoted as solution A；
2) 150g hydroxypropylβ-cyclodextrin and 40g mannitol are added in solution A, obtains solution B；
3) 160g polylactic acid and 40g polyethylene glycol 200 are dissolved in 160g 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 salbutamol 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 80.70% that gained sample, which measures encapsulation rate, carrying drug ratio 50.50%, body
Outer release experiment proves that this preparation energy slow release salbutamol, salbutamol are finally discharged up to 90% or more, sees Fig. 2.
Embodiment three:
1) 100g salbutamol is dissolved in 160g95% ethyl alcohol, obtains salbutamol ethanol solution, is denoted as solution A；
2) 160g hydroxypropylβ-cyclodextrin and 50g mannitol are added in solution A, obtains solution B；
3) 170g polylactic acid and 50g polyethylene glycol 200 are dissolved in 170g 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 salbutamol 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 81.02% that gained sample, which measures encapsulation rate, carrying drug ratio 51.19%, body
Outer release experiment proves that this preparation energy slow release salbutamol, salbutamol 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 salbutamol sustained release preparation, it is characterised in that the salbutamol sustained release preparation is by husky butylamine
Alcohol, hydroxypropylβ-cyclodextrin, polylactic acid, mannitol, polyethylene glycol 200,95% ethyl alcohol, acetone composition.
2. the preparation method of salbutamol sustained release preparation as described in claim 1, it is characterised in that the steps include:
1) salbutamol is dissolved in 95% ethyl alcohol, obtains albuterol solution, be 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 salbutamol sustained release preparation with low temperature spray drying legal system.
3. salbutamol sustained release preparation each component as claimed in claim 1 or 2 contains salbutamol 100 by weight, contain 95%
Ethyl alcohol 140~160 contains hydroxypropylβ-cyclodextrin 140~160, contains mannitol 30~50, contains acetone 150~170, contains polylactic acid
150~170, contain polyethylene glycol 200 30~50.
4. the preparation method of salbutamol 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 salbutamol 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.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711109358.8A CN108992420A (en) | 2017-11-11 | 2017-11-11 | A kind of preparation method of salbutamol sustained release preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711109358.8A CN108992420A (en) | 2017-11-11 | 2017-11-11 | A kind of preparation method of salbutamol sustained release preparation |
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| Publication Number | Publication Date |
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| CN108992420A true CN108992420A (en) | 2018-12-14 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201711109358.8A Withdrawn CN108992420A (en) | 2017-11-11 | 2017-11-11 | A kind of preparation method of salbutamol sustained release preparation |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110124043A (en) * | 2019-05-17 | 2019-08-16 | 南京望知星医药科技有限公司 | A kind of salbutamol sulfate and preparation method thereof |
| CN110151682A (en) * | 2019-05-17 | 2019-08-23 | 南京望知星医药科技有限公司 | A kind of salbutamol and preparation method thereof |
-
2017
- 2017-11-11 CN CN201711109358.8A patent/CN108992420A/en not_active Withdrawn
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110124043A (en) * | 2019-05-17 | 2019-08-16 | 南京望知星医药科技有限公司 | A kind of salbutamol sulfate and preparation method thereof |
| CN110151682A (en) * | 2019-05-17 | 2019-08-23 | 南京望知星医药科技有限公司 | A kind of salbutamol and preparation method thereof |
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