CN109010314A - A kind of preparation method of indapamide slow release preparation - Google Patents

A kind of preparation method of indapamide slow release preparation Download PDF

Info

Publication number
CN109010314A
CN109010314A CN201711109437.9A CN201711109437A CN109010314A CN 109010314 A CN109010314 A CN 109010314A CN 201711109437 A CN201711109437 A CN 201711109437A CN 109010314 A CN109010314 A CN 109010314A
Authority
CN
China
Prior art keywords
solution
indapamide
preparation
temperature
hours
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
CN201711109437.9A
Other languages
Chinese (zh)
Inventor
刘丽
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Individual
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Individual filed Critical Individual
Priority to CN201711109437.9A priority Critical patent/CN109010314A/en
Publication of CN109010314A publication Critical patent/CN109010314A/en
Withdrawn legal-status Critical Current

Links

Classifications

    • 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
    • A61K31/403—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 condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • 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
    • 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

Landscapes

  • 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)
  • Medicinal Preparation (AREA)

Abstract

The present invention provides a kind of preparation method of indapamide slow release preparation, the steps include: to be dissolved in indapamide 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 indapamide 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

A kind of preparation method of indapamide slow 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 indapamide slow 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.
Indapamide is sulfamido diuretics, has diuresis and calcium antagonism, is a kind of potent, long-acting depressor, Can be relaxed vascular smooth muscle by retardance Ca2+ influx, declined peripheral vascular resistance, generated pressure reduction effect；This medicine passes through inhibition Distal renal tubular cortex dilution section reabsorbs water and electrolyte and plays diuresis.Clinically it is also used to hypertension and oedema. This medicine low dosage sustained-release dosage type is identical as the anti-hypertension curative effect of agent clinically is released, and sustained release agent causes the hair of hypopotassaemia Raw rate is lower by 50% or more than releasing agent.Constant slow release at a predetermined rate after the administration of indapamide oral slow-releasing preparation, and Unlike conventional formulation can rapid delivery of pharmaceuticals.With corresponding ordinary preparation, such as fast-release tablet, capsule, oral solution is compared, and can be improved The compliance of patient simultaneously increases curative effect of medication.The major advantage of sustained release preparation is can to reduce dosage frequency and avoid taking general The blood concentration peak valley phenomenon that logical preparation occurs.Sustained release preparation can keep blood concentration to stablize within the relatively long time Within the scope of effective blood drug concentration, to improve Drug safety.Indapamide slow release preparation mainly uses skeleton agent skill at present Art production, commonly uses ethyl cellulose, acrylic resin, lactose, the auxiliary materials such as microcrystalline cellulose.But the dosage form produced with such technology There are the risks that drug release during burst release and storage changes, and supplementary product consumption is big, is unfavorable for taking orally.One is provided to this for clinic Safe and effective, reliable in quality, high production efficiency are planted, supplementary product consumption is moderate, and the stable indapamide slow release preparation of drug release is very It is necessary in consideration of it, propose 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 indapamide 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 indapamide slow release preparation, which is characterized in that the sustained release preparation by indapamide, hydroxypropylβ-cyclodextrin, Polylactic acid, mannitol, polyethylene glycol 200,95% ethyl alcohol and acetone composition.The indapamide slow release preparation each component is by weight Amount containing 95% ethyl alcohol 130~150, contains hydroxypropylβ-cyclodextrin 130~150, contains mannitol 20~30 than containing indapamide 100, 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 indapamide slow release preparation, which is characterized in that The specific steps of this method are as follows:
1) indapamide is dissolved in 95% ethyl alcohol, obtains indapamide 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 indapamide slow release preparation with low temperature spray drying legal system.
Indapamide slow release preparation of the invention is passed through to be released with the cumulative in vitro of commercially available same dosage form indapamide slow release preparation Dose comparative study, it was demonstrated that indapamide slow release preparation medicine 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 indapamide slow 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 indapamide slow 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 indapamide slow 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 indapamide slow release preparation.
Embodiment one:
1) 100g indapamide is dissolved in 130g95% ethyl alcohol, obtains indapamide ethanol solution, is denoted as solution A；
2) 130g 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 indapamide slow 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 80.62% that gained sample, which measures encapsulation rate, carrying drug ratio 50.61%, body Outer release experiment proves that this preparation energy slow release indapamide, indapamide are finally discharged up to 90% or more, sees Fig. 1.
Embodiment two:
1) 100g indapamide is dissolved in 140g95% ethyl alcohol, obtains indapamide ethanol solution, is denoted as solution A；
2) 140g 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 indapamide slow 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 80.18% that gained sample, which measures encapsulation rate, carrying drug ratio 51.20%, body Outer release experiment proves that this preparation energy slow release indapamide, indapamide are finally discharged up to 90% or more, sees Fig. 2.
Embodiment three:
1) 100g indapamide is dissolved in 150g95% ethyl alcohol, obtains indapamide ethanol solution, is denoted as solution A；
2) 150g 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 indapamide slow release preparation, the temperature of spray drying with low temperature spray drying legal system Degree 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 81.08% that gained sample, which measures encapsulation rate, carrying drug ratio 51.22%, body Outer release experiment proves that this preparation energy slow release indapamide, indapamide 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 indapamide slow release preparation, it is characterised in that the indapamide slow release preparation reaches pa by Yin Amine, hydroxypropylβ-cyclodextrin, polylactic acid, mannitol, polyethylene glycol 200,95% ethyl alcohol, acetone composition.
2. the preparation method of indapamide slow release preparation as described in claim 1, it is characterised in that the steps include:
1) indapamide is dissolved in 95% ethyl alcohol, obtains indapamide 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 indapamide slow release preparation with low temperature spray drying legal system.
3. indapamide slow release preparation each component as claimed in claim 1 or 2 contains indapamide 100 by weight, contain 95% Ethyl alcohol 130~150 contains hydroxypropylβ-cyclodextrin 130~150, contains mannitol 20~30, contains acetone 130~150, contains polylactic acid 130~150, contain polyethylene glycol 200 20~40.
4. the preparation method of indapamide slow 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 indapamide slow 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.
CN201711109437.9A 2017-11-11 2017-11-11 A kind of preparation method of indapamide slow release preparation Withdrawn CN109010314A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201711109437.9A CN109010314A (en) 2017-11-11 2017-11-11 A kind of preparation method of indapamide slow release preparation

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201711109437.9A CN109010314A (en) 2017-11-11 2017-11-11 A kind of preparation method of indapamide slow release preparation

Publications (1)

Publication Number Publication Date
CN109010314A true CN109010314A (en) 2018-12-18

Family

ID=64630128

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201711109437.9A Withdrawn CN109010314A (en) 2017-11-11 2017-11-11 A kind of preparation method of indapamide slow release preparation

Country Status (1)

Country Link
CN (1) CN109010314A (en)

Similar Documents

Publication Publication Date Title
US11013694B2 (en) Formulation of a micro drop pill and the preparation method thereof
CN109010312A (en) A kind of preparation method of sustained-release theophylline preparation
CN108992420A (en) A kind of preparation method of salbutamol sustained release preparation
CN108992427A (en) A kind of preparation method of Flurbiprofen sustained release preparation
CN109010316A (en) A kind of preparation method of vitamin B 6 sustained release preparation
CN109010314A (en) A kind of preparation method of indapamide slow release preparation
CN108992408A (en) A kind of preparation method of body of Pramipexole dihydrochloride sustained release preparation
CN108992394A (en) A kind of preparation method of pseudoephedrine hydrochloride slow release preparation
CN108992409A (en) A kind of preparation method of metformin hydrochloride slow release preparation
CN108992428A (en) A kind of preparation method of felodipine sustained-release preparation
CN109010277A (en) A kind of preparation method of oxycodone hydrochloride sustained release preparation
CN109010315A (en) A kind of preparation method of Etodolac sustained release preparation
CN109010278A (en) A kind of preparation method of Nifedipine sustained-release preparation
CN108992423A (en) A kind of preparation method of tamsulosin hydrochloride sustained release preparation
CN108992421A (en) A kind of preparation method of methylphenidate hydrochloride sustained release preparation
CN109010286A (en) A kind of preparation method of niacin sustained-release preparation
CN108992426A (en) A kind of preparation method of 9-hydroxy-risperidone sustained release preparation
CN108992461A (en) A kind of preparation method of potassium chloride sustained release preparation
CN101249082B (en) Preparation of acidum citricum tamoxifen polylactic acid-glycolic co-polymer microballoons
CN108992424A (en) A kind of preparation method of nevirapine sustained release preparation
CN108992407A (en) A kind of preparation method of aminophylline sustained release preparation
CN108992406A (en) A kind of preparation method of ropinirole hydrochloride sustained release preparation
CN108992397A (en) A kind of preparation method of Propranolol sustained release preparation
CN108992395A (en) A kind of preparation method of verapamil hydrochloride sustained release preparation
CN108992410A (en) A kind of preparation method of Buflomedil Hydrochloride sustained release preparation

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
WW01 Invention patent application withdrawn after publication

Application publication date: 20181218

WW01 Invention patent application withdrawn after publication