CN108992410A - A kind of preparation method of Buflomedil Hydrochloride sustained release preparation - Google Patents
A kind of preparation method of Buflomedil Hydrochloride sustained release preparation Download PDFInfo
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- CN108992410A CN108992410A CN201711109341.2A CN201711109341A CN108992410A CN 108992410 A CN108992410 A CN 108992410A CN 201711109341 A CN201711109341 A CN 201711109341A CN 108992410 A CN108992410 A CN 108992410A
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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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
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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
- A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
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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
- A61K9/1629—Organic macromolecular compounds
- A61K9/1641—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
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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
- A61K9/1629—Organic macromolecular compounds
- A61K9/1641—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
- A61K9/1647—Polyesters, e.g. 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
- A61K9/14—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
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
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- Pharmacology & Pharmacy (AREA)
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- Animal Behavior & Ethology (AREA)
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- Biophysics (AREA)
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- Medicinal Preparation (AREA)
Abstract
The present invention provides a kind of preparation method of Buflomedil Hydrochloride sustained release preparation, the steps include: to be dissolved in Buflomedil Hydrochloride 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 Buflomedil Hydrochloride 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 Buflomedil Hydrochloride sustained release systems
The preparation method of agent.
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.
Buflomedil Hydrochloride is a kind of vasoactive agent with a variety of pharmacotoxicological effects, the main function of buflomedil
To inhibit alpha adrenergic receptor, inhibiting platelet aggregation, enhancing red cell deformability, non-specific calcium antagonism and increasing
The utilization of strong oxygen, so as to improve ischemic tissue's nutritional blood flow.It is extensive to be mainly used for cerebral vessels hardening, cerebral infarction, cerebrovascular accident
Multiple phase and sequela stage, vascular dementia, dizziness.Peripheral artery disease, such as intermittent claudication, vasculitis.Buflomedil Hydrochloride
Constant slow release at a predetermined rate after oral slow-releasing preparation administration, can rapid delivery of pharmaceuticals rather than conventional formulation.With phase
The ordinary preparation answered, such as fast-release tablet, capsule, oral solution are compared, and the compliance of patient can be improved and increase curative effect of medication.Sustained release
The major advantage of preparation is the blood concentration peak valley phenomenon that can be reduced dosage frequency and avoid taking ordinary preparation appearance.It is slow
Release formulation can keep blood concentration to stablize within the scope of effective blood drug concentration within the relatively long time, to improve drug
Safety.Buflomedil Hydrochloride sustained release preparation mainly uses skeleton agent technology to produce at present, commonly uses ethyl cellulose, acrylic acid
Resin, lactose, the auxiliary materials such as microcrystalline cellulose.But drug release changes during the dosage form produced with such technology has burst release and storage
The risk of change, 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 Buflomedil Hydrochloride 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 Buflomedil Hydrochloride 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 Buflomedil Hydrochloride sustained release preparation, which is characterized in that the sustained release preparation is by Buflomedil Hydrochloride, hydroxypropyl beta-
Cyclodextrin, polylactic acid, mannitol, polyethylene glycol 200,95% ethyl alcohol and acetone composition.The Buflomedil Hydrochloride is sustained system
Agent each component contains 95% ethyl alcohol 100~120 by weight hydrochloric buflomedil 100, containing hydroxypropylβ-cyclodextrin 110~
130, contain mannitol 20~30, contain acetone 150~170, contain polylactic acid 150~170, contains polyethylene glycol 200 20~40, it is described
Polylactic acid relative molecular weight is 5000~20000.
It is a further object to provide a kind of method for being prepared into Buflomedil Hydrochloride sustained release preparation, feature exists
In the specific steps of this method are as follows:
1) Buflomedil Hydrochloride is dissolved in 95% ethyl alcohol, obtains Buflomedil Hydrochloride 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 Buflomedil Hydrochloride sustained release preparation with low temperature spray drying legal system.
Buflomedil Hydrochloride sustained release preparation of the invention is through the body with commercially available same dosage form Buflomedil Hydrochloride sustained release preparation
Outer cumulative release amount comparative study, it was demonstrated that Buflomedil Hydrochloride sustained release preparation drug release of the invention is more stable, slow-release function
More preferably.And preparation method high production efficiency, capsule material dosage is moderate, and dry materials temperature is low, and obtained carrying medicine is uniform in size,
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 Buflomedil Hydrochloride sustained release preparation.In Fig. 1, abscissa is time (hour), indulges and sits
It is designated as 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 Buflomedil Hydrochloride sustained release preparation.In Fig. 2, abscissa is time (hour), indulges and sits
It is designated as 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 Buflomedil Hydrochloride sustained release preparation.In Fig. 3, abscissa is time (hour), indulges and sits
It is designated as 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 Buflomedil Hydrochloride sustained release preparation.
Embodiment one:
1) 100g Buflomedil Hydrochloride is dissolved in 100g95% ethyl alcohol, obtains Buflomedil Hydrochloride ethanol solution, be denoted as molten
Liquid A；
2) 110g hydroxypropylβ-cyclodextrin and 20g mannitol are added in solution A, obtains solution B；
3) 150g polylactic acid and 20g 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 Buflomedil Hydrochloride sustained release preparation with low temperature spray drying legal system, be spray-dried
Temperature control 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 80.46% that gained sample, which measures encapsulation rate, carrying drug ratio 50.11%, body
Outer release experiment proves this preparation energy slow release Buflomedil Hydrochloride, Buflomedil Hydrochloride finally discharge reachable 90% with
On, see Fig. 1.
Embodiment two:
1) 100g Buflomedil Hydrochloride is dissolved in 110g95% ethyl alcohol, obtains Buflomedil Hydrochloride ethanol solution, be denoted as molten
Liquid A；
2) 120g hydroxypropylβ-cyclodextrin and 25g mannitol are added in solution A, obtains solution B；
3) 160g polylactic acid and 30g 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 Buflomedil Hydrochloride sustained release preparation with low temperature spray drying legal system, be spray-dried
Temperature control 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 80.41% that gained sample, which measures encapsulation rate, carrying drug ratio 50.53%, body
Outer release experiment proves this preparation energy slow release Buflomedil Hydrochloride, Buflomedil Hydrochloride finally discharge reachable 90% with
On, see Fig. 2.
Embodiment three:
1) 100g Buflomedil Hydrochloride is dissolved in 120g95% ethyl alcohol, obtains Buflomedil Hydrochloride ethanol solution, be denoted as molten
Liquid A；
2) 130g hydroxypropylβ-cyclodextrin and 30g mannitol are added in solution A, obtains solution B；
3) 170g polylactic acid and 40g 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 Buflomedil Hydrochloride 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 81.21% that gained sample, which measures encapsulation rate, carrying drug ratio 51.08%, body
Outer release experiment proves this preparation energy slow release Buflomedil Hydrochloride, Buflomedil Hydrochloride finally discharge reachable 90% with
On, see 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 Buflomedil Hydrochloride sustained release preparation, it is characterised in that the Buflomedil Hydrochloride sustained release preparation
It is made of Buflomedil Hydrochloride, hydroxypropylβ-cyclodextrin, polylactic acid, mannitol, polyethylene glycol 200,95% ethyl alcohol, acetone.
2. the preparation method of Buflomedil Hydrochloride sustained release preparation as described in claim 1, it is characterised in that the steps include:
1) Buflomedil Hydrochloride is dissolved in 95% ethyl alcohol, obtains Buflomedil Hydrochloride 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 Buflomedil Hydrochloride sustained release preparation with low temperature spray drying legal system.
3. Buflomedil Hydrochloride sustained release preparation each component as claimed in claim 1 or 2 is by weight hydrochloric buflomedil
100, contain 95% ethyl alcohol 100~120, contain hydroxypropylβ-cyclodextrin 110~130, contains mannitol 20~30, containing acetone 150~
170, contain polylactic acid 150~170, contains polyethylene glycol 200 20~40.
4. the preparation method of Buflomedil Hydrochloride sustained release preparation as claimed in claim 1 or 2, it is characterised in that the phase of polylactic acid
It is 5000~20000 to molecular weight.
5. the preparation method of Buflomedil Hydrochloride sustained release preparation as claimed in claim 3, it is characterised in that low temperature spray drying
Temperature be 55 DEG C~60 DEG C, nozzle diameter be 0.5mm~1mm, hothouse vacuum degree be 0.03MPA~0.04MPA, solution D
Flow is 500ml/ hours~1000ml/ hours.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711109341.2A CN108992410A (en) | 2017-11-11 | 2017-11-11 | A kind of preparation method of Buflomedil Hydrochloride sustained release preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711109341.2A CN108992410A (en) | 2017-11-11 | 2017-11-11 | A kind of preparation method of Buflomedil Hydrochloride sustained release preparation |
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| Publication Number | Publication Date |
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| CN108992410A true CN108992410A (en) | 2018-12-14 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201711109341.2A Withdrawn CN108992410A (en) | 2017-11-11 | 2017-11-11 | A kind of preparation method of Buflomedil Hydrochloride sustained release preparation |
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- 2017-11-11 CN CN201711109341.2A patent/CN108992410A/en not_active Withdrawn
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Application publication date: 20181214 |