CN104434892A - Naproxen dispersible tablet - Google Patents
Naproxen dispersible tablet Download PDFInfo
- Publication number
- CN104434892A CN104434892A CN201410637707.3A CN201410637707A CN104434892A CN 104434892 A CN104434892 A CN 104434892A CN 201410637707 A CN201410637707 A CN 201410637707A CN 104434892 A CN104434892 A CN 104434892A
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- CN
- China
- Prior art keywords
- naproxen
- clathrate
- dispersible tablet
- beta
- schardinger dextrin
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- 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.)
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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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6949—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
- A61K47/6951—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes using cyclodextrin
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention discloses a method for preparing a naproxen dispersible tablet. The method comprises the steps of preparing an inclusion compound from naproxen, and then preparing the dispersible tablet.
Description
Technical field
The present invention relates to a kind of preparation method of naproxen dispersible tablets.
Background technology
Naproxen has another name called (+)-Alpha-Methyl-6-methoxyl-2-naphthylacetic acid, is a kind of NSAID (non-steroidal anti-inflammatory drug), has the effect of antipyretic-antalgic antiinflammatory, can suppress the synthesis of prostaglandin and play anti-inflammatory and analgesic effect.For alleviating mild to moderate pain, as arthralgia, neuralgia, myalgia, migraine, headache, dysmenorrhea, toothache.This product is dissolved in methanol/ethanol, does not dissolve in water.
Dispersible tablet is put into after water can disintegrate rapidly, forms the ground suspension that is uniformly dispersed, has easy to use, the feature that bioavailability is high.The preparation method of dispersible tablet, working condition and production technology are simple, and instructions of taking is convenient, can swallow as conventional tablet, also can be distributed to wet suit and use.
Summary of the invention
The invention provides a kind of preparation method of naproxen dispersible tablets; This injection has the features such as solubility is good, good stability, and drug loading is high, safety of clinical trials is good, overcomes the deficiencies in the prior art part.
Dispersible tablet is relative to conventional tablet, and in disintegrate medium, disintegration is less than 3 minutes, and the granule after disintegrate can all by No. 2 sieves, and compared with capsule preparations, it is rapid that dispersible tablet has stripping, absorb fast, the advantages such as bioavailability is high, taking convenience.
Clathrate has the following advantages: cover bad stink, reduces zest; Increase drug dissolution and bioavailability; Improve medicine stability.
Naproxen is first prepared into clathrate by the application, and then prepared composition discrete piece, enclose and dispersion technology is united two into one, and plays the advantage of two aspects.
Naproxen clathrate comprises active component and enclose material, and active component is naproxen, and enclose material is alpha-cyclodextrin, beta-schardinger dextrin-, hydroxyl beta-schardinger dextrin-, one or more of hydroxypropylβ-cyclodextrin.The part by weight of active component and enclose material is 3:2-2:3.
The present invention also adopts the special adjuvant of dispersible tablet, and disintegrate is rapid, rapid-action.
The preparation method of naproxen clathrate comprises:
(1) in water or aquiferous ethanol medium, by a certain percentage, by naproxen and alpha-cyclodextrin, beta-schardinger dextrin-, hydroxyl beta-schardinger dextrin-, one or more reactions of hydroxypropylβ-cyclodextrin, by gained solution through filtering with microporous membrane extremely clarification, from mixture, isolate clathrate; Or (2) are in solid form, by naproxen and alpha-cyclodextrin, beta-schardinger dextrin-, hydroxyl beta-schardinger dextrin-, one or more reactions of hydroxypropylβ-cyclodextrin; Or (3) naproxen and alpha-cyclodextrin, beta-schardinger dextrin-, hydroxyl beta-schardinger dextrin-, high energy milling is carried out in one or more reactions of hydroxypropylβ-cyclodextrin.
By the above-mentioned naproxen clathrate prepared composition discrete piece prepared, described dispersible tablet comprises by weight, the disintegrating agent of 1-30%, the filler of 1-80%, the lubricant of 0.1-5%, the fluidizer of 0.1-5%, the flavouring agent of 0.1-5%, all the other are naproxen clathrate.Particularly, disintegrating agent is polyvinylpolypyrrolidone or sodium carboxymethyl cellulose, and filler is microcrystalline Cellulose or mannitol, and lubricant is magnesium stearate or Pulvis Talci, and fluidizer is micropowder silica gel, and flavouring agent is cyclamate or fruit essence.Preferably, disintegrating agent is polyvinylpolypyrrolidone, and filler is mannitol, and the ratio of the two is 3:2, can significantly improve the preparation effect of dispersible tablet when adopting the adjuvant of this specific proportioning, accelerates disintegration rate.
Metering of the present invention is weight.
PVP20％；
Mannitol 10%;
Magnesium stearate 2%;
Micropowder silica gel 1%;
Naproxen clathrate surplus.
Detailed description of the invention
Embodiment 1: a kind of naproxen dispersible tablets
Naproxen clathrate: beta-schardinger dextrin-is 2:3
The prescription of dispersible tablet is (by weight):
PVP20％；
Mannitol 10%;
Magnesium stearate 2%;
Micropowder silica gel 1%;
Naproxen clathrate surplus.
Preparation method:
1. prepare naproxen clathrate by the following method:
(1) in water or aquiferous ethanol medium, by a certain percentage, naproxen and hydroxypropylβ-cyclodextrin are reacted, by gained solution through filtering with microporous membrane extremely clarification, from mixture, isolate clathrate; Or (2) in solid form, naproxen and hydroxypropylβ-cyclodextrin are reacted; Or (3) naproxen and hydroxypropylβ-cyclodextrin react and carry out high energy milling.
2. by the polyvinylpolypyrrolidone of recipe quantity, mannitol, after cyclamate is mixed homogeneously by the equivalent method of progressively increasing with naproxen clathrate, then adds magnesium stearate, micropowder silica gel, and mixing, tabletting, obtains naproxen clathrate dispersible tablet.
Embodiment 2: a kind of naproxen dispersible tablets
Naproxen clathrate: beta-schardinger dextrin-is 2:3
The prescription of dispersible tablet is (by weight):
Sodium carboxymethyl cellulose 20%;
Mannitol 10%;
Magnesium stearate 2%;
Micropowder silica gel 1%;
Naproxen clathrate surplus.
Preparation method:
1. prepare naproxen clathrate by the following method:
(1) in water or aquiferous ethanol medium, by a certain percentage, naproxen and hydroxypropylβ-cyclodextrin are reacted, by gained solution through filtering with microporous membrane extremely clarification, from mixture, isolate clathrate; Or (2) in solid form, naproxen and hydroxypropylβ-cyclodextrin are reacted; Or (3) naproxen and hydroxypropylβ-cyclodextrin react and carry out high energy milling.
2. by the polyvinylpolypyrrolidone of recipe quantity, mannitol, after cyclamate is mixed homogeneously by the equivalent method of progressively increasing with naproxen clathrate, then adds magnesium stearate, micropowder silica gel, and mixing, tabletting, obtains naproxen clathrate dispersible tablet.
Embodiment 3: a kind of naproxen dispersible tablets
Naproxen clathrate: beta-schardinger dextrin-is 2:3
The prescription of dispersible tablet is (by weight):
Sodium carboxymethyl cellulose 20%;
Mannitol 10%;
Magnesium stearate 2%;
Micropowder silica gel 1%;
Naproxen clathrate surplus.
Preparation method is the same
The analytical test result of naproxen clathrate dispersible tablet prepared by the above embodiment of the present invention:
(1) weight differential of the naproxen clathrate dispersible tablet of embodiment 1,2 preparation is little, and unilateral bright and clean, hardness is moderate, and mouthfeel is good.Naproxen dispersible tablets weight differential prepared by embodiment 3 is little, and unilateral injustice, hardness is little, and mouthfeel is slightly poor.
(2) naproxen described in embodiment 1,2 and hydroxypropylβ-cyclodextrin are fully ground in 50% ethanol the even mastic of formation, after vacuum drying, obtain white powder, in the water of this powder, the naproxen of the more non-enclose of solubility property improves 12 times.
(3) dispersing uniformity experimental result display: according to the method for 2010 editions Chinese Pharmacopoeias two regulation, Example 1,2,3 each 6, puts in 250ml beaker, adds the water 100mL of about 20 DEG C, jolting 90 seconds, the whole disintegrate of embodiment 1,2 dispersible tablet also passes through No. two sieves.100% is shortened than 3 minute time limit of States Pharmacopoeia specifications.Embodiment 3 dispersible tablet jolting whole disintegrate by No. two sieves after 4 minutes.
(4) dissolution test result display: according to dissolution method (Chinese Pharmacopoeia 2010 editions two annex XC second methods), using 0.01mol/L hydrochloric acid solution 900ml as dissolution medium, rotating speed is 50 revs/min, operate in accordance with the law, every sheet stripping quantity is measured according to ultraviolet visible spectrophotometry, result be the stripping percentage rate of embodiment 1,2 dispersible tablet in 60 seconds at about 80-90%, substantially all strippings in 90 seconds.Embodiment 3 dispersible tablet after 3 minutes stripping percentage rate about 80%, basic all strippings in 5 minutes.
Result shows, naproxen clathrate dispersible tablet provided by the invention meets the regulation of Chinese Pharmacopoeia (2000 editions) about dispersible tablet.Vitamin C clathrate dispersible tablet has outstanding excellent water dissolubility and dispersion effect compared to naproxen, and according to polyvinylpolypyrrolidone: mannitol is that clathrate dispersible tablet prepared by 3:2 has more outstanding excellent dispersion effect relative to the dispersible tablet of this special ratios non-.
Embodiment 4: droplet measurement
The injection of Example 1-3, is dissolved in water into the solution of every 1mL containing 1mg naproxen, measures with laser diffraction particle size instrument.The naproxen injection that acetonideexample 1-3 prepares is spherical shape, and even particle size distribution, whole particle diameter is between 300-550nm.
Embodiment 5: envelop rate detects
The injection of naproxen is dissolved in water into the solution of every 1mL containing naproxen 1mg, with the centrifugation 15min of 6000r/min, gets supernatant 1mL, with dissolve with ethanol, measure the content of naproxen.
Dose in envelop rate=microsphere/(dose in the dose+medium in microsphere) × 100%
The envelop rate of injection prepared by embodiment 1-3, between 80%-90%.
Embodiment 6: dissolution velocity is investigated
Each two bottles of injection in random selecting embodiment 1-3, numbering 1-6, sample number into spectrum 7 after physical mixed, the naproxen freeze-dried powder numbering 8 of having gone on the market, by the dissolving method of clinical application, inject 10mL water for injection respectively, eddy mixer jolts, completely clear and bright for index to dissolve, calculate dissolution velocity.
Experimental result shows that the dissolution velocity of injection of the present invention is obviously better than the injection of direct packaging.
Embodiment 7: study on the stability
The injection that the sample prepared by embodiment 1-3 and raw material directly mix subpackage is placed in high temperature 40 DEG C, lower 6 months of relative humidity 75% ± 5% condition respectively, carries out acceleration and investigates.
Claims (1)
1. a naproxen dispersible tablets, is characterized in that the prescription of dispersible tablet is by weight:
PVP20％；
Mannitol 10%;
Magnesium stearate 2%;
Micropowder silica gel 1%;
Naproxen clathrate surplus;
Wherein naproxen in naproxen clathrate: beta-schardinger dextrin-is 2:3;
Preparation method is as follows:
1). prepare naproxen clathrate by the following method:
(1) in water or aquiferous ethanol medium, by a certain percentage, naproxen and beta-schardinger dextrin-are reacted, by gained solution through filtering with microporous membrane extremely clarification, from mixture, isolate clathrate; Or (2) in solid form, naproxen and beta-schardinger dextrin-are reacted; Or (3) naproxen and beta-schardinger dextrin-react and carry out high energy milling;
2). by the polyvinylpolypyrrolidone of recipe quantity, mannitol, after cyclamate is mixed homogeneously by the equivalent method of progressively increasing with naproxen clathrate, then adds magnesium stearate, micropowder silica gel, and mixing, tabletting, obtains naproxen clathrate dispersible tablet.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410637707.3A CN104434892A (en) | 2014-11-10 | 2014-11-10 | Naproxen dispersible tablet |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410637707.3A CN104434892A (en) | 2014-11-10 | 2014-11-10 | Naproxen dispersible tablet |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN104434892A true CN104434892A (en) | 2015-03-25 |
Family
ID=52882158
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410637707.3A Pending CN104434892A (en) | 2014-11-10 | 2014-11-10 | Naproxen dispersible tablet |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104434892A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106361714A (en) * | 2016-11-24 | 2017-02-01 | 江苏中邦制药有限公司 | Preparation method of medicine composition containing naproxen |
| CN107281499A (en) * | 2017-07-25 | 2017-10-24 | 广东省药品检验所（广东省药品质量研究所、广东省口岸药品检验所） | A kind of method for improving pharmaceutic adjuvant beta cyclodextrin inclusion characteristic |
-
2014
- 2014-11-10 CN CN201410637707.3A patent/CN104434892A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106361714A (en) * | 2016-11-24 | 2017-02-01 | 江苏中邦制药有限公司 | Preparation method of medicine composition containing naproxen |
| CN107281499A (en) * | 2017-07-25 | 2017-10-24 | 广东省药品检验所（广东省药品质量研究所、广东省口岸药品检验所） | A kind of method for improving pharmaceutic adjuvant beta cyclodextrin inclusion characteristic |
| CN107281499B (en) * | 2017-07-25 | 2020-12-01 | 广东省药品检验所（广东省药品质量研究所、广东省口岸药品检验所） | Method for improving beta-cyclodextrin inclusion performance of pharmaceutic adjuvant |
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Application publication date: 20150325 |