CN109010312A - A kind of preparation method of sustained-release theophylline preparation - Google Patents
A kind of preparation method of sustained-release theophylline preparation Download PDFInfo
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- CN109010312A CN109010312A CN201711109336.1A CN201711109336A CN109010312A CN 109010312 A CN109010312 A CN 109010312A CN 201711109336 A CN201711109336 A CN 201711109336A CN 109010312 A CN109010312 A CN 109010312A
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- solution
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- sustained
- theophylline
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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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
- A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
-
- 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)
-
- 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
Abstract
The present invention provides a kind of preparation method of sustained-release theophylline preparation, the steps include: to be dissolved in theophylline 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 sustained-release theophylline 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 preparations of sustained-release theophylline 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.
Theophylline is methyl purine class drug.With heart tonifying, diuresis, coronary artery dilator, relaxation bronchial smooth muscle and emerging
The effects of central nervous system of putting forth energy.It is mainly used for treating bronchial asthma, pulmonary emphysema, bronchitis, cardiac dyspnea.Tea
Constant slow release at a predetermined rate after the administration of alkali 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.Sustained-release theophylline 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 sustained-release theophylline 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 sustained-release theophylline 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 sustained-release theophylline preparation, which is characterized in that the sustained release preparation is by theophylline, hydroxypropylβ-cyclodextrin, polylactic acid, sweet
Reveal alcohol, polyethylene glycol 200,95% ethyl alcohol and acetone composition.The sustained-release theophylline preparation each component contains theophylline by weight
100, contain 95% ethyl alcohol 150~170, contain hydroxypropylβ-cyclodextrin 150~170, contains mannitol 20~30, containing acetone 130~
150, contain polylactic acid 130~150, contain polyethylene glycol 200 20~40, the polylactic acid relative molecular weight is 5000~20000.
It is a further object to provide a kind of methods for being prepared into sustained-release theophylline preparation, which is characterized in that the party
The specific steps of method are as follows:
1) theophylline is dissolved in 95% ethyl alcohol, obtains theophylline 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 sustained-release theophylline preparation with low temperature spray drying legal system.
Sustained-release theophylline preparation of the invention is passed through to be compared with the extracorporeal accumulating released medicine of commercially available same dosage form sustained-release theophylline preparation
Research, it was demonstrated that sustained-release theophylline preparation medicine release of the invention is more stable, and slow-release function is more preferable.And preparation method production efficiency
Height, 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%, and 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 sustained-release theophylline preparation.In Fig. 1, abscissa is time (hour), and ordinate is accumulation
Drug 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 sustained-release theophylline preparation.In Fig. 2, abscissa is time (hour), and ordinate is accumulation
Drug 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 sustained-release theophylline preparation.In Fig. 3, abscissa is time (hour), and ordinate is accumulation
Drug 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 sustained-release theophylline preparation.
Embodiment one:
1) 100g theophylline is dissolved in 150g95% ethyl alcohol, obtains theophylline ethanol solution, is denoted as solution A；
2) 150g hydroxypropylβ-cyclodextrin and 20g mannitol are added in solution A, obtains solution B；
3) 130g polylactic acid and 20g polyethylene glycol 200 are dissolved in 130g 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 sustained-release theophylline preparation, the temperature control of spray drying with low temperature spray drying legal system
System 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 80.22% that gained sample, which measures encapsulation rate, carrying drug ratio 50.16%, body
Outer release experiment proves that this preparation energy slow release theophylline, theophylline are finally discharged up to 90% or more, sees Fig. 1.
Embodiment two:
1) 100g theophylline is dissolved in 160g95% ethyl alcohol, obtains theophylline ethanol solution, is denoted as solution A；
2) 160g hydroxypropylβ-cyclodextrin and 25g mannitol are added in solution A, obtains solution B；
3) 140g polylactic acid and 30g polyethylene glycol 200 are dissolved in 140g 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 sustained-release theophylline preparation, the temperature control of spray drying with low temperature spray drying legal system
System 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 80.37% that gained sample, which measures encapsulation rate, carrying drug ratio 50.51%, body
Outer release experiment proves that this preparation energy slow release theophylline, theophylline are finally discharged up to 90% or more, sees Fig. 2.
Embodiment three:
1) 100g theophylline is dissolved in 170g95% ethyl alcohol, obtains theophylline ethanol solution, is denoted as solution A；
2) 170g hydroxypropylβ-cyclodextrin and 30g mannitol are added in solution A, obtains solution B；
3) 150g polylactic acid and 40g 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 sustained-release theophylline preparation, the temperature control of spray drying with low temperature spray drying legal system
System is at 60 DEG C, nozzle diameter: 1mm, vacuum degree: 0.04MPA, flow: 1000ml/ hours.
Sample obtained by low temperature spray drying is taken, it is 81.67% that gained sample, which measures encapsulation rate, carrying drug ratio 51.38%, body
Outer release experiment proves that this preparation energy slow release theophylline, theophylline 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 sustained-release theophylline preparation, it is characterised in that the sustained-release theophylline preparation is by theophylline, hydroxypropyl beta-
Cyclodextrin, polylactic acid, mannitol, polyethylene glycol 200,95% ethyl alcohol, acetone composition.
2. the preparation method of sustained-release theophylline preparation as described in claim 1, it is characterised in that the steps include:
1) theophylline is dissolved in 95% ethyl alcohol, obtains theophylline 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 sustained-release theophylline preparation with low temperature spray drying legal system.
3. sustained-release theophylline preparation each component as claimed in claim 1 or 2 contains theophylline 100 by weight, containing 95% ethyl alcohol 150~
170, contain hydroxypropylβ-cyclodextrin 150~170, contain mannitol 20~30, contain acetone 130~150, contains polylactic acid 130~150,
Containing polyethylene glycol 200 20~40.
4. the preparation method of sustained-release theophylline preparation as claimed in claim 1 or 2, it is characterised in that the relative molecular weight of polylactic acid
It is 5000~20000.
5. the preparation method of sustained-release theophylline preparation as claimed in claim 3, it is characterised in that the temperature of low temperature spray drying is
55 DEG C~60 DEG C, nozzle diameter is 0.5mm~1mm, and hothouse vacuum degree is 0.03MPA~0.04MPA, and solution D flow is
500ml/ hours~1000ml/ hours.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711109336.1A CN109010312A (en) | 2017-11-11 | 2017-11-11 | A kind of preparation method of sustained-release theophylline preparation |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201711109336.1A CN109010312A (en) | 2017-11-11 | 2017-11-11 | A kind of preparation method of sustained-release theophylline preparation |
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| Publication Number | Publication Date |
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| CN109010312A true CN109010312A (en) | 2018-12-18 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN201711109336.1A Withdrawn CN109010312A (en) | 2017-11-11 | 2017-11-11 | A kind of preparation method of sustained-release theophylline preparation |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112190498A (en) * | 2020-10-31 | 2021-01-08 | 华南理工大学 | Water-soluble theophylline and cyclodextrin inclusion compound and preparation method thereof |
| CN113679690A (en) * | 2021-09-06 | 2021-11-23 | 复旦大学附属中山医院 | Theophylline dry powder preparation and preparation method and application thereof |
-
2017
- 2017-11-11 CN CN201711109336.1A patent/CN109010312A/en not_active Withdrawn
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112190498A (en) * | 2020-10-31 | 2021-01-08 | 华南理工大学 | Water-soluble theophylline and cyclodextrin inclusion compound and preparation method thereof |
| CN112190498B (en) * | 2020-10-31 | 2022-03-25 | 华南理工大学 | Water-soluble theophylline and cyclodextrin inclusion compound and preparation method thereof |
| CN113679690A (en) * | 2021-09-06 | 2021-11-23 | 复旦大学附属中山医院 | Theophylline dry powder preparation and preparation method and application thereof |
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