CN108992461A - A kind of preparation method of potassium chloride sustained release preparation - Google Patents

A kind of preparation method of potassium chloride sustained release preparation Download PDF

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Publication number
CN108992461A
CN108992461A CN201711109372.8A CN201711109372A CN108992461A CN 108992461 A CN108992461 A CN 108992461A CN 201711109372 A CN201711109372 A CN 201711109372A CN 108992461 A CN108992461 A CN 108992461A
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solution
potassium chloride
preparation
sustained release
temperature
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刘丽
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/14—Alkali metal chlorides; Alkaline earth metal chlorides
    • 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

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  • Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Inorganic Chemistry (AREA)
  • Medicinal Preparation (AREA)

Abstract

The preparation method that the present invention provides a kind of potassium chloride sustained release preparation the steps include: to be dissolved in potassium chloride 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 potassium chloride 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

A kind of preparation method of potassium chloride sustained release preparation
Technical field:
The present invention relates to a kind of pharmaceutical preparation of medicine-carrying polymer preparation more particularly to a kind of systems of potassium chloride sustained release preparation 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.
Potassium chloride is that electrolyte balance adjusts medicine, is clinically used for hypopotassaemia caused by treating and preventing a variety of causes, also It is not normal to can be used for frequent, polyphyly premature beat or rapid heart rate caused by the poisoning by cardiotonic glycoside such as the heart, renal edema and digitalis. Constant slow release at a predetermined rate after the administration of potassium chloride oral slow-releasing preparation, can quick release medicine rather than conventional formulation Object.With corresponding ordinary preparation, such as fast-release tablet, capsule, oral solution is compared, and the compliance of patient can be improved and increase drug treatment Effect.The major advantage of sustained release preparation is the blood concentration peak valley that can be reduced dosage frequency and avoid taking ordinary preparation appearance Phenomenon.Sustained release preparation can keep blood concentration to stablize within the scope of effective blood drug concentration within the relatively long time, thus Improve Drug safety.Potassium chloride sustained release preparation mainly uses skeleton agent technology to produce at present, commonly uses ethyl cellulose, propylene Acid resin, lactose, the auxiliary materials such as microcrystalline cellulose.But drug release during there is burst release and storage with the dosage form that such technology produces The risk of change, and supplementary product consumption is big, is unfavorable for taking orally.Safe and effective one kind, reliable in quality, production effect are provided to this for clinic Rate is high, and supplementary product consumption is moderate, and the stable potassium chloride 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 potassium chloride 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 potassium chloride sustained release preparation, which is characterized in that the sustained release preparation is by potassium chloride, hydroxypropylβ-cyclodextrin, poly- cream Acid, mannitol, polyethylene glycol 200,95% ethyl alcohol and acetone composition.The potassium chloride sustained release preparation each component contains by weight Potassium chloride 100 contains 95% ethyl alcohol 100~130, contains hydroxypropylβ-cyclodextrin 100~130, contains mannitol 20~30, contains acetone 120~150, contain polylactic acid 120~150, contain polyethylene glycol 200 20~40, the polylactic acid relative molecular weight be 5000~ 20000。
It is a further object to provide a kind of methods for being prepared into potassium chloride sustained release preparation, which is characterized in that should The specific steps of method are as follows:
1) potassium chloride is dissolved in 95% ethyl alcohol, obtains Klorvess Liquid, 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 potassium chloride sustained release preparation with low temperature spray drying legal system.
Potassium chloride sustained release preparation of the invention is through the extracorporeal accumulating released medicine with commercially available same dosage form potassium chloride sustained release preparation Comparative study, it was demonstrated that potassium chloride sustained release preparation drug release of the invention is more stable, and slow-release function is more preferable.And preparation method is raw Produce high-efficient, capsule material dosage is moderate, and dry materials temperature is low, is made that carrying medicine is uniform in size, and encapsulation rate is greater than 80%, carries medicine Amount 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 potassium chloride sustained release preparation.In Fig. 1, abscissa is time (hour), and ordinate is tired Product 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 potassium chloride sustained release preparation.In Fig. 2, abscissa is time (hour), and ordinate is tired Product 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 potassium chloride sustained release preparation.In Fig. 3, abscissa is time (hour), and ordinate is tired Product 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 potassium chloride sustained release preparation.
Embodiment one:
1) 100g potassium chloride is dissolved in 100g95% ethyl alcohol, obtains potassium chloride ethanol solution, is denoted as solution A；
2) 100g 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 potassium chloride sustained release preparation, the temperature of spray drying with low temperature spray drying legal system 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 80.56% that gained sample, which measures encapsulation rate, carrying drug ratio 50.34%, body Outer release experiment proves that this preparation energy slow release potassium chloride, potassium chloride are finally discharged up to 90% or more, sees Fig. 1.
Embodiment two:
1) 100g potassium chloride is dissolved in 115g95% ethyl alcohol, obtains potassium chloride ethanol solution, is denoted as solution A；
2) 115g 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 potassium chloride sustained release preparation, the temperature of spray drying with low temperature spray drying legal system 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 80.72% that gained sample, which measures encapsulation rate, carrying drug ratio 51.09%, body Outer release experiment proves that this preparation energy slow release potassium chloride, potassium chloride are finally discharged up to 90% or more, sees Fig. 2.
Embodiment three:
1) 100g potassium chloride is dissolved in 130g95% ethyl alcohol, obtains potassium chloride ethanol solution, is denoted as solution 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 potassium chloride sustained release preparation, the temperature of spray drying with low temperature spray drying legal system Control 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 81.59% that gained sample, which measures encapsulation rate, carrying drug ratio 51.62%, body Outer release experiment proves that this preparation energy slow release potassium chloride, potassium chloride 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 potassium chloride sustained release preparation, it is characterised in that the potassium chloride sustained release preparation is by potassium chloride, hydroxyl Propyl beta-cyclodextrin, polylactic acid, mannitol, polyethylene glycol 200,95% ethyl alcohol, acetone composition.
2. the preparation method of potassium chloride sustained release preparation as described in claim 1, it is characterised in that the steps include:
1) potassium chloride is dissolved in 95% ethyl alcohol, obtains Klorvess Liquid, 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 potassium chloride sustained release preparation with low temperature spray drying legal system.
3. potassium chloride sustained release preparation each component as claimed in claim 1 or 2 contains 95% ethyl alcohol by weight chloride containing potassium 100 100~130, contain hydroxypropylβ-cyclodextrin 100~130, contain mannitol 20~30, contains acetone 120~150, containing polylactic acid 120~ 150, contain polyethylene glycol 200 20~40.
4. the preparation method of potassium chloride sustained release preparation as claimed in claim 1 or 2, it is characterised in that the average molecular of polylactic acid Amount is 5000~20000.
5. the preparation method of potassium chloride sustained release preparation as claimed in claim 3, it is characterised in that the temperature of low temperature spray drying It 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.
CN201711109372.8A 2017-11-11 2017-11-11 A kind of preparation method of potassium chloride sustained release preparation Withdrawn CN108992461A (en)

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