CN108992394A - A kind of preparation method of pseudoephedrine hydrochloride slow release preparation - Google Patents
A kind of preparation method of pseudoephedrine hydrochloride slow release preparation Download PDFInfo
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- CN108992394A CN108992394A CN201711109559.8A CN201711109559A CN108992394A CN 108992394 A CN108992394 A CN 108992394A CN 201711109559 A CN201711109559 A CN 201711109559A CN 108992394 A CN108992394 A CN 108992394A
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- pseudoephedrine hydrochloride
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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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds
Abstract
The present invention provides a kind of preparation method of pseudoephedrine hydrochloride slow release preparation, and pseudoephedrine hydrochloride is dissolved 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 pseudoephedrine hydrochloride slow 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 pseudoephedrine hydrochloride slow 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.
Pseudoephedrine hydrochloride is sympathetic transmitter releasers, and sympathetic nerve endings can be stimulated to discharge norepinephrine, thus with
Indirectly-acting mode plays sympatheticomimetic action.The vasoconstrictor effects of this product have certain selectivity, exhale on main shrinkage
Road blood vessel is inhaled, the hyperemia of pharynx nasalis mucous membrane is eliminated, can preferably mitigate the congested phenomenon of upper respiratory tract mucous membrane.This product is flat to bronchus
The dilating effect of sliding flesh and systemic vasoconstriction effect are weak compared with ephedrine hydrochloride.It is clinically used for allergic rhinitis, rhinitis, nasosinusitis
Control, bronchial asthma etc..Constant slow release at a predetermined rate after the administration of pseudoephedrine hydrochloride oral slow-releasing preparation, without
As conventional formulation can rapid delivery of pharmaceuticals.With corresponding ordinary preparation, such as fast-release tablet, capsule, oral solution is compared, and trouble can be improved
The compliance of person simultaneously increases curative effect of medication.The major advantage of sustained release preparation is can to reduce dosage frequency and avoid taking common
The blood concentration peak valley phenomenon that preparation occurs.Sustained release preparation can keep blood concentration stabilization having within the relatively long time
It imitates within the scope of blood concentration, to improve Drug safety.Pseudoephedrine hydrochloride slow release preparation mainly uses skeleton agent at present
Technology production, commonly uses ethyl cellulose, acrylic resin, lactose, the auxiliary materials such as microcrystalline cellulose.But the agent produced with such technology
The risk that drug release changes during type has burst release and storage, and supplementary product consumption is big, is unfavorable for taking orally.This is provided for clinic
A kind of safe and effective, reliable in quality, high production efficiency, supplementary product consumption is moderate, the stable pseudoephedrine hydrochloride slow release of drug release
Preparation 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 pseudoephedrine hydrochloride slow 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 pseudoephedrine hydrochloride slow release preparation, which is characterized in that the sustained release preparation is by pseudoephedrine hydrochloride, hydroxypropyl beta-
Cyclodextrin, polylactic acid, mannitol, polyethylene glycol 200,95% ethyl alcohol and acetone composition.The pseudoephedrine hydrochloride slow release system
Agent each component contains 95% ethyl alcohol 120~130 by weight hydrochloric pseudoephedrine 100, containing hydroxypropylβ-cyclodextrin 120~
130, contain mannitol 20~30, contain acetone 120~150, contain polylactic acid 120~150, 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 pseudoephedrine hydrochloride slow release preparation, feature exists
In the specific steps of this method are as follows:
1) pseudoephedrine hydrochloride is dissolved in 95% ethyl alcohol, obtains pseudoephedrine 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 pseudoephedrine hydrochloride slow release preparation with low temperature spray drying legal system.
Pseudoephedrine hydrochloride slow release preparation of the invention is through the body with commercially available same dosage form pseudoephedrine hydrochloride slow release preparation
Outer cumulative release amount comparative study, it was demonstrated that pseudoephedrine hydrochloride slow 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 pseudoephedrine hydrochloride slow 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 pseudoephedrine hydrochloride slow 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 pseudoephedrine hydrochloride slow 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 pseudoephedrine hydrochloride slow release preparation.
Embodiment one:
1) 100g pseudoephedrine hydrochloride is dissolved in 120g95% ethyl alcohol, obtains pseudoephedrine hydrochloride ethanol solution, be denoted as molten
Liquid A；
2) 120g hydroxypropylβ-cyclodextrin and 20g mannitol are added in solution A, obtains solution B；
3) 120g polylactic acid and 20g polyethylene glycol 200 are dissolved in 120g 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 pseudoephedrine hydrochloride slow 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 80.53% that gained sample, which measures encapsulation rate, carrying drug ratio 50.41%, body
Outer release experiment proves this preparation energy slow release pseudoephedrine hydrochloride, pseudoephedrine hydrochloride finally discharge reachable 90% with
On, see Fig. 1.
Embodiment two:
1) 100g pseudoephedrine hydrochloride is dissolved in 125g95% ethyl alcohol, obtains pseudoephedrine hydrochloride ethanol solution, be denoted as molten
Liquid A；
2) 125g hydroxypropylβ-cyclodextrin and 25g mannitol are added in solution A, obtains solution B；
3) 135g polylactic acid and 30g polyethylene glycol 200 are dissolved in 135g 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 pseudoephedrine hydrochloride slow 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 80.70% that gained sample, which measures encapsulation rate, carrying drug ratio 50.93%, body
Outer release experiment proves this preparation energy slow release pseudoephedrine hydrochloride, pseudoephedrine hydrochloride finally discharge reachable 90% with
On, see Fig. 2.
Embodiment three:
1) 100g pseudoephedrine hydrochloride is dissolved in 130g95% ethyl alcohol, obtains pseudoephedrine 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) 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 pseudoephedrine hydrochloride slow 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 81.22% that gained sample, which measures encapsulation rate, carrying drug ratio 51.34%, body
Outer release experiment proves this preparation energy slow release pseudoephedrine hydrochloride, pseudoephedrine 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 pseudoephedrine hydrochloride slow release preparation, it is characterised in that the pseudoephedrine hydrochloride slow release preparation
It is made of pseudoephedrine hydrochloride, hydroxypropylβ-cyclodextrin, polylactic acid, mannitol, polyethylene glycol 200,95% ethyl alcohol, acetone.
2. the preparation method of pseudoephedrine hydrochloride slow release preparation as described in claim 1, it is characterised in that the steps include:
1) pseudoephedrine hydrochloride is dissolved in 95% ethyl alcohol, obtains pseudoephedrine 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 pseudoephedrine hydrochloride slow release preparation with low temperature spray drying legal system.
3. pseudoephedrine hydrochloride slow release preparation each component as claimed in claim 1 or 2 is by weight hydrochloric pseudoephedrine
100, contain 95% ethyl alcohol 120~130, contain hydroxypropylβ-cyclodextrin 120~130, contains mannitol 20~30, containing acetone 120~
150, contain polylactic acid 120~150, contains polyethylene glycol 200 20~40.
4. the preparation method of pseudoephedrine hydrochloride slow 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 pseudoephedrine hydrochloride slow 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.
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| CN201711109559.8A CN108992394A (en) | 2017-11-11 | 2017-11-11 | A kind of preparation method of pseudoephedrine hydrochloride slow release preparation |
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| CN201711109559.8A CN108992394A (en) | 2017-11-11 | 2017-11-11 | A kind of preparation method of pseudoephedrine hydrochloride slow release preparation |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114533662A (en) * | 2022-01-19 | 2022-05-27 | 南昌立健药业有限公司 | Compound pholcodine oral solution and preparation method thereof |
-
2017
- 2017-11-11 CN CN201711109559.8A patent/CN108992394A/en not_active Withdrawn
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114533662A (en) * | 2022-01-19 | 2022-05-27 | 南昌立健药业有限公司 | Compound pholcodine oral solution and preparation method thereof |
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