CN105935445A - 2-(-4-isobutylphenyl)propionic acid dextrogyre-containing pharmaceutical composition and preparation method thereof - Google Patents
2-(-4-isobutylphenyl)propionic acid dextrogyre-containing pharmaceutical composition and preparation method thereof Download PDFInfo
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- CN105935445A CN105935445A CN201610189107.4A CN201610189107A CN105935445A CN 105935445 A CN105935445 A CN 105935445A CN 201610189107 A CN201610189107 A CN 201610189107A CN 105935445 A CN105935445 A CN 105935445A
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- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
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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
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- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
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- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
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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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2009—Inorganic compounds
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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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
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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
- A61K9/48—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
- A61K9/501—Inorganic compounds
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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
- A61K9/48—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
- A61K9/5042—Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
Abstract
The invention discloses a 2-(-4-isobutylphenyl)propionic acid dextrogyre-containing pharmaceutical composition and a preparation method thereof; the pharmaceutical composition comprises the components and the contents: 30-80 wt% of a 2-(-4-isobutylphenyl)propionic acid dextrogyre, and 1-25 wt% of a disintegrant. According to the 2-(-4-isobutylphenyl)propionic acid dextrogyre-containing pharmaceutical composition, through reasonable proportion of the disintegrant, an adhesive agent and a filler, the pharmaceutical composition has good absorbing performance and stability, bitter taste of the 2-(-4-isobutylphenyl)propionic acid dextrogyre and other peculiar tastes after the pharmaceutical composition is put into a mouth are covered, the medication compliance of patients is improved, and an effect for better curing diseases is achieved.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition containing 2-(-4-isobutyl phenenyl) propanoic acid dextrogyre and preparation method thereof.
Background technology
2-(-4-isobutyl phenenyl) propanoic acid, has another name called Ibuprofen, ibuprofen, ibuprofen, its have antiinflammatory, analgesia,
Refrigeration function.Rheumatism and rheumatoid arthritis can be treated.
Owing to ibuprofen includes levo form and d-isomer, and mainly come according to the pharmacologically active of pertinent literature record ibuprofen
From d-isomer i.e. 2-(-4-isobutyl phenenyl) propanoic acid dextrogyre, its levo form does not have pharmacological action, and side effect is unknown, the most whole
There is room for promotion, and the existence of levo form in the drug effect of the individual pharmaceutical composition with ibuprofen as main component, also gives
It brings the risk that there is certain side effect.
Summary of the invention
In order to solve above-mentioned technical problem, the invention provides and a kind of may be adapted to tabletted or be filled in capsule
Pharmaceutical composition containing 2-(-4-isobutyl phenenyl) propanoic acid dextrogyre and preparation method thereof, this pharmaceutical composition is without bitterness, release
Uniformly, good dispersing state, belong to NSAID (non-steroidal anti-inflammatory drug), have antipyretic, analgesia and antiinflammatory action.
According to an aspect of the invention, it is provided a kind of medicine group containing 2-(-4-isobutyl phenenyl) propanoic acid dextrogyre
Compound, specifically includes following components and constituent content:
2-(-4-isobutyl phenenyl) propanoic acid dextrogyre 30～80wt%；
Disintegrating agent 1～25wt%；
Wherein, pharmaceutical composition also includes:
Binding agent 1～10wt%；
Filler 20～60wt%；
Wherein, disintegrating agent includes polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, carboxymethylcellulose calcium, carboxymethylstarch
One or both in one or more in sodium, the most preferably carboxymethylcellulose calcium, cross-linking sodium carboxymethyl cellulose.
Wherein, during binding agent includes hydroxypropyl methylcellulose, hydroxypropyl cellulose, polyvidone, corn starch or water
Plant or several, the most preferably hydroxypropyl methylcellulose；
Filler includes one or more in microcrystalline Cellulose, corn starch, calcium phosphate.
According to another aspect of the present invention, it is provided that the preparation method of this pharmaceutical composition a kind of, comprise the following steps:
(1) by 2-(-4-isobutyl phenenyl) propanoic acid dextrogyre and disintegrating agent micronization respectively, and be dry mixed be formed uniformly mixed
Powder, the particle diameter controlling 2-(-4-isobutyl phenenyl) propanoic acid dextrogyre micropowder is 120～180 μm, controls the particle diameter of disintegrating agent micropowder
Less than or equal to 180 μm so that the composition of mixed powder is full and uniform；
(2) in mixed powder, add a part of binding agent make fine pellet core, control the particle diameter of fine pellet core be 0.1～
0.7mm, preferably 0.3～0.5mm；
(3) by a part of filler micronization, and mix to uniformly with another part binding agent, make spraying solvent；
(4) use the mode of bed spray, spraying solvent is homogeneously applied to the surface of fine pellet core, makes medicine
Core.
Wherein, step (4) including:
Use peristaltic pump that spraying solvent is sent into fluid bed, make it be atomized by the way of compressed air purges, use top
Spray or the method for end spray, be sprayed at the surface of fine pellet core equably by spraying solvent, and drying prepares medicated core, wherein, and spraying
The spray velocity of solvent is 2.5～3.5mL/min*cm2, and spray amount is 4～6cm2/mL.
Wherein, step (3) including:
The particle diameter controlling filler micropowder is 80～120 μm, preferably 95～105 μm.
Wherein, step (1) including:
Another part filler is micronized to particle diameter and is less than or equal to 180 μm, by micronized 2-(-4-isobutyl phenenyl)
Propanoic acid dextrogyre, disintegrating agent and another part filler are dry mixed the mixed powder of formation so that mixed powder is full and uniform.
Wherein, step (4) including: controlling the temperature of fine pellet core in fluid bed is 40～46 DEG C, preferably 43～45 DEG C；
Step (2) including: adds a part of binding agent in mixed powder and makes soft material, and is made by extrusion and spheronization step
Fine pellet core, the temperature and the round as a ball temperature that control extrusion are 30～45 DEG C, are preferably all 39～42 DEG C.
Wherein, preparation method also includes being positioned at the step after step (4): (5) add lubricant in medicated core periphery, are formed
Pharmaceutical composition.
Wherein, disintegrating agent is used for making pharmaceutical composition disintegrate, discharges principal agent, and disintegrating agent is too low, and pharmaceutical composition cannot be real
Now fully disintegrate, affects dissolving and the absorption of main component, and disintegrating agent is too high, easily produces gathering, mixed inequality, can affect granule
Mobility so that drug particles weight differential is big, and disintegrating agent too much easily causes the easy moisture absorption of pharmaceutical composition, gives storage
Deposit and cause difficulty, affect the stability of pharmaceutical composition.In the present invention, it is adaptable to 2-(-4-isobutyl phenenyl) propanoic acid dextrogyre
Disintegrating agent include the one in polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, carboxymethylcellulose calcium, carboxymethylstach sodium or
Several.And in the present invention, when the content of disintegrating agent is 1～25wt%, this contains 2-(-4-isobutyl phenenyl) propanoic acid dextrogyre
The dissolving of pharmaceutical composition, absorption, stability are best.
Binding agent acts primarily as the effect of bonding and moistening, on the one hand makes the principal agent being dry mixed and adjuvant prepare through moistening suitable
Soft material, make it suitable for round as a ball, on the other hand can make filler stick to round as a ball after the surface of fine pellet core reach taste masking,
The effect of protection medicine capsule core.In the present invention, it is adaptable to the binding agent of 2-(-4-isobutyl phenenyl) propanoic acid dextrogyre includes hydroxypropyl
One or more in methylcellulose, hydroxypropyl cellulose, polyvidone, corn starch or water.And in the present invention, binding agent
Content be suitable between 1～10wt%, can be easy with pelletizing forming, and make granulation density reach optimum.
Filler, by preparing the excipient that solid preparation is added, mainly works in molding, is also called diluent, is coated with
Cover the surface with fine pellet core and be mainly used in removing the bitterness of 2-(-4-isobutyl phenenyl) propanoic acid dextrogyre, due to the increasing of medicine
Important have clearly control, to control the divided dose of formation solid preparation, add the weightening finish scope after filler under normal circumstances and exist
Between 5-25%, therefore the weight of filler is different according to the specification of types of drugs and the difference of the composition of weighting agent, this
In invention, the Suitable ingredients content of filler is 20～60wt%.
During actual pharmacy, when tablet press or capsule charge, in order to ensure tablet weight or charging quantity, also need to add
Add the pulverulent solids that ensure that medicated core proper flow, i.e. lubricant.In the present invention, the suitable addition of lubricant is medicine
Between 0.5～2% of core weight, preferably 0.8～1.2%, in the present invention, the loading of lubricant accounts for 2-(-4-isobutyl group
Phenyl) propanoic acid dextrogyre and disintegrating agent consumption summation 0.5～10%.
It addition, the homogeneity of principal agent composition release is the key factor affecting drug effect in pharmaceutical technology, containing 2-, (-4-is different
Butyl phenyl) propanoic acid dextrogyre pharmaceutical composition preparation method in, disintegrating agent and principal agent composition 2-(-4-in dry mixing step
Isobutyl phenenyl) whether uniformly and the particle diameter of fine pellet core made is the pass affecting homogeneity for the mixing of propanoic acid dextrogyre
Key.
In actual pharmacy procedure, whether disintegrating agent and principal agent composition mix is often difficult to judge, inventor is by big
The experiment of amount and Data Comparison find, principal agent composition is crushed to 120～180 μm, and disintegrating agent is crushed to less than 180 μm, then takes
Join the mixing operation of routine, sufficient Blending Efficiency of Blending can be reached.
Additionally, the spray effect of bed spray process is also another key factor affecting homogeneity, and fine pellet core
Size directly related with spray effect, fine pellet core is too small, and spraying is uniform not, the coated uniformity of filler, micropill ball
Core is excessive, and fluid bed blows afloat more difficult, is coated effect the most bad.In the present invention, between fine pellet core 0.1～0.7mm, preferably
Between 0.3～0.5mm, it is possible to being uniformly distributed of each composition of guarantee pharmaceutical composition.
The spray effect of bed spray process also with the direct phase of degree of mode, the speed of atomization and atomization of atomization
Closing, the fusing point simultaneously taking account of the 2-as primary raw material (-4-isobutyl phenenyl) propanoic acid dextrogyre only has 48～52 DEG C, therefore
Answer strict temperature control when operations, during using fluid bed, strict temperature control to be less than 45 DEG C, because of
This, the dosage sprayed in the present invention, speed, fogging degree need with the temperature of charge of fluid bed adapts, and are ensureing principal agent
Non-fusible on the premise of, it is ensured that the attachment of filler is uniform, is dried rapidly.
It addition, the particle diameter of filler micropowder is also the key factor affecting atomizing effect in spraying solvent.By strict control
Making these pharmacy parameters, the present invention is by the control to process above parameter so that the pharmaceutical composition finally prepared reaches equal
The effect of one release.
The pharmaceutical composition containing 2-(-4-isobutyl phenenyl) propanoic acid dextrogyre of the present invention has the advantage that
(1) use relatively little of dosage i.e. to can reach the curative effect of ibuprofen, and reduce ibuprofen levorotatory side effect
Risk；
(2) by disintegrating agent, binding agent and the rational proportion of filler, pharmaceutical composition is made to have good absorbability
Can and stability, mask other abnormal flavour after the bitterness of 2-(-4-isobutyl phenenyl) propanoic acid dextrogyre and entrance thereof, improve
Patient medication compliance, reaches more preferably to cure the effect of illness.
(3) by new production thinking, new technology, improve the result of extraction of principal agent and reached the mesh of homogeneous release
's.
Specific embodiment
For making the purpose of the embodiment of the present invention, technical scheme and advantage clearer, to the technology in the embodiment of the present invention
Scheme is clearly and completely described, it is clear that described embodiment is a part of embodiment of the present invention rather than whole
Embodiment.Based on the embodiment in the present invention, those of ordinary skill in the art are obtained under not making creative work premise
The every other embodiment obtained, broadly falls into the scope of protection of the invention.It should be noted that in the case of not conflicting, this Shen
Embodiment in please and the feature in embodiment can mutual combination in any.
Embodiment 1 pharmaceutical composition X1
The prescription of pharmaceutical composition X1:
| Supplementary material | Recipe quantity (mg) |
| Dexibuprofen | 75 |
| Microcrystalline Cellulose (another part filler) | 138 |
| Hydroxypropyl methylcellulose (binding agent) | 19.5 |
| Cross-linking sodium carboxymethyl cellulose (disintegrating agent) | 2.5 |
| Calcium phosphate (a part of filler) | 12 |
| Magnesium stearate (lubricant) | 3 |
| Element tablet weight | 250 |
The preparation technology of pharmaceutical composition X1:
(1) dexibuprofen is ground into 150 μm, crosses 100 mesh sieves；By cross-linking sodium carboxymethyl cellulose, microcrystal cellulose powder
It is broken into about 180 μm, crosses 80 mesh sieves；Three is put in three-dimensional mixer and mix 15 minutes, make mixed powder.
(2) prepare the hydroxypropyl methylcellulose solution of 1% concentration as binding agent, a part therein is added to mixed powder
In, be prepared as soft material, soft material be extruded in an extruder strip, extrusion temperature is 45 DEG C, be re-fed in spheronizator cutting,
Round as a ball, control round as a ball temperature between 30～45 DEG C, be eventually fabricated the oval fine pellet core of diameter about 0.1mm.
(3) powder that microcrystalline Cellulose is broken into 80 μm puts in another part binding agent, is prepared as suspension, to turn
Son coordinates magnetic stirring apparatus not stop stirring, to ensure uniformly.
(4) fine pellet core is put in fluid bed, blow afloat, with peristaltic pump, suspension is squeezed into fluid bed, with compressed air
Purging atomization, is also homogeneously applied to the surface of fine pellet core by suspendible, makes the medicated core that particle diameter is 0.15mm, controls micropill ball
The temperature of core is between 43～45 DEG C, and the spray velocity of spraying solvent is 2.5ml/min*cm2, spray amount be 4.0cm2/ml。
(5) add magnesium stearate in medicated core periphery and make the drug regimen containing 2-(-4-isobutyl phenenyl) propanoic acid dextrogyre
Thing X1, with Φ 10mm punch die tabletting.
Testing result:
(1) tablet appearance is good, hardness is good；
(2) disintegration time is 13 minutes, dissolution=88%, RSD=1.5.
Embodiment 2 pharmaceutical composition X2
The prescription of pharmaceutical composition X2:
| Supplementary material | Recipe quantity (mg) |
| Dexibuprofen | 420 |
| Hydroxypropyl cellulose (binding agent) | 65 |
| Cross-linking sodium carboxymethyl cellulose (disintegrating agent) | 6.5 |
| Corn starch (filler) | 117 |
| Magnesium stearate (lubricant) | 41.5 |
| Element tablet weight | 650 |
The preparation technology of pharmaceutical composition X2:
(1) dexibuprofen is ground into 120 μm, crosses 120 mesh sieves；Cross-linking sodium carboxymethyl cellulose is ground into 170 μm, mistake
80 mesh sieves；The two is put in three-dimensional mixer and mix 15 minutes, make mixed powder.
(2) prepare the hydroxypropyl cellulose solution of 4% concentration as binding agent, a part therein is added to mixed powder
In, it being prepared as soft material, soft material is extruded in an extruder strip, extrusion temperature is positioned at 39～42 DEG C, is re-fed into spheronizator
Middle cutting, round as a ball, control round as a ball temperature and be positioned at 39～42 DEG C, be eventually fabricated the oval fine pellet core of diameter about 0.7mm.
(3) powder that microcrystalline Cellulose is broken into 80 μm puts in another part binding agent, is prepared as suspension, to turn
Son coordinates magnetic stirring apparatus not stop stirring, to ensure uniformly.
(4) fine pellet core is put in fluid bed, blow afloat, with peristaltic pump, suspension is squeezed into fluid bed, with compressed air
Purging atomization, the temperature controlling fine pellet core is positioned at 40～46 DEG C, and the spray velocity of spraying solvent is 3ml/min*cm2, spraying
Amount is 4.8cm2/ ml, prepared particle diameter is the medicated core of 0.9mm.
(5) add magnesium stearate in medicated core periphery and make the drug regimen containing 2-(-4-isobutyl phenenyl) propanoic acid dextrogyre
Thing X2, with Φ 10mm punch die tabletting.
Testing result:
(1) tablet appearance is good, hardness is good；
(2) disintegration time is 8 minutes, dissolution=95%, RSD=1.1.
Embodiment 3 pharmaceutical composition X3
The prescription of pharmaceutical composition X3:
| Supplementary material | Recipe quantity (mg) |
| Dexibuprofen | 200 |
| Calcium phosphate (filler) | 87 |
| Polyvidone (binding agent) | 16 |
| Carboxymethylstach sodium (disintegrating agent) | 22 |
| Silicon dioxide (lubricant) | 20 |
| Pulvis Talci (lubricant) | 3 |
| Element tablet weight | 348 |
The preparation technology of pharmaceutical composition X3:
(1) dexibuprofen is ground into 180 μm, crosses 80 mesh sieves；Carboxymethylstach sodium, is ground into 150 μm, crosses 100 mesh sieves；Will
The two is put in three-dimensional mixer and mixes 15 minutes, makes mixed powder.
(2) povidone solution of 1% concentration is prepared as binding agent, by part addition therein to mixing in powder, preparation
Become soft material, soft material is extruded in an extruder strip, extrusion temperature is 40 DEG C, be re-fed in spheronizator cutting, round as a ball, control
Making round as a ball temperature is 40 DEG C, is eventually fabricated the oval fine pellet core of diameter about 0.3mm.
(3) powder that calcium phosphate is broken into 95 μm puts in another part binding agent, is prepared as suspension, joins with rotor
Close magnetic stirring apparatus and do not stop stirring, to ensure uniformly.
(4) fine pellet core is put in fluid bed, blow afloat, with peristaltic pump, suspension is squeezed into fluid bed, with compressed air
Purging atomization, controlling temperature of charge is 44 DEG C, and the spray velocity of spraying solvent is 3.5ml/min*cm2, atomization quantity be 5.0cm2/
Ml, prepared particle diameter is the medicated core of 0.45mm.
(5) add silicon dioxide in medicated core periphery and Pulvis Talci is made containing 2-(-4-isobutyl phenenyl) propanoic acid dextrogyre
Pharmaceutical composition X4, with Φ 10mm punch die tabletting.
Testing result:
(1) tablet appearance is good, and hardness is good；
(2) disintegration time is 3 minutes, dissolution=98%, RSD=0.8.
Embodiment 4 pharmaceutical composition X4
The prescription of pharmaceutical composition X4:
| Supplementary material | Recipe quantity (mg) |
| Dexibuprofen | 100 |
| Corn starch (filler) | 154.52 |
| Water (binding agent) | 3.48 |
| Carboxymethylstach sodium (disintegrating agent) | 87 |
| Silicon dioxide (lubricant) | 3 |
| Element tablet weight | 348 |
The preparation technology of pharmaceutical composition X4:
(1) dexibuprofen is ground into 180 μm, crosses 80 mesh sieves；Carboxymethylstach sodium, corn starch, be ground into 150 μm, mistake
100 mesh sieves；Three is put in three-dimensional mixer and mix 15 minutes, make mixed powder.
(2) prepare the carboxymethylcellulose calcium solution of 4% concentration as binding agent, a part therein is added to mixed powder
In, it being prepared as soft material, soft material is extruded in an extruder strip, extrusion temperature is less than 40 DEG C, is re-fed in spheronizator cutting
Cut, round as a ball, control round as a ball temperature less than 42 DEG C, be eventually fabricated the oval fine pellet core of diameter about 0.5mm.
(3) powder that microcrystalline Cellulose is broken into 105 μm puts in another part binding agent, is prepared as suspension, with
Rotor engagement magnetic stirring apparatus does not stop stirring, to ensure uniformly.
(4) fine pellet core is put in fluid bed, blow afloat, with peristaltic pump, suspension is squeezed into fluid bed, with compressed air
Purging atomization, controls temperature of charge and is less than 40 DEG C, and the spray velocity of spraying solvent is 2.9ml/min*cm2, spray amount be 6cm2/
Ml, prepared particle diameter is 0.75mm medicated core.
(5) add silicon dioxide in medicated core periphery and make the drug regimen containing 2-(-4-isobutyl phenenyl) propanoic acid dextrogyre
Thing X4, with Φ 10mm punch die tabletting.
(1) tablet appearance is good, hardness is good；
(2) disintegration time is 3 minutes, dissolution=97%, RSD=0.7.
Embodiment 5 pharmaceutical composition X5
The prescription of pharmaceutical composition X5:
| Supplementary material | Recipe quantity |
| Dexibuprofen | 200 |
| Microcrystalline Cellulose (filler) | 80 |
| Hydroxypropyl methylcellulose (binding agent) | 20 |
| Carboxymethylstach sodium (disintegrating agent) | 25 |
| Corn starch (filler) | 20 |
| Magnesium stearate (lubricant) | 3 |
| Element tablet weight | 348 |
The preparation technology of pharmaceutical composition X5:
(1) dexibuprofen is pulverized, cross 100 mesh sieves；Carboxymethylstach sodium, corn starch, pulverized 80 mesh sieves；Three is put
Three-dimensional mixer mixes 15 minutes, makes mixed powder.
(2) prepare the hydroxypropyl methylcellulose solution of 4% concentration as binding agent, a portion added in mixed powder,
Be prepared as soft material, soft material be extruded in an extruder strip, extrusion temperature be less than 40 DEG C, be re-fed in spheronizator cutting,
Round as a ball, control round as a ball temperature and be less than 40 DEG C, be eventually fabricated the oval fine pellet core of diameter about 0.5mm.
(3) powder that microcrystalline Cellulose is broken into 100 μm puts in another part binding agent, is prepared as suspension, with
Rotor engagement magnetic stirring apparatus does not stop stirring, to ensure uniformly.
(4) fine pellet core is put in fluid bed, blow afloat, with peristaltic pump, suspension is squeezed into fluid bed, with compressed air
Purging atomization, controls temperature of charge and is less than 45 DEG C, and atomization speed is 3.5ml/min*cm2, fogging degree be 5.6cm2/ ml, prepares
Particle diameter is 0.8mm medicated core.
(5) add silicon dioxide in medicated core periphery and make the drug regimen containing 2-(-4-isobutyl phenenyl) propanoic acid dextrogyre
Thing X5, with Φ 10mm punch die tabletting.
Testing result:
(1) tablet appearance is good, hardness is good；
(2) disintegration time is 13 minutes, dissolution=87%, RSD=1.4.
Embodiment 6 pharmaceutical composition X6
The prescription of pharmaceutical composition X6:
| Supplementary material | Recipe quantity |
| Dexibuprofen | 200 |
| Microcrystalline Cellulose (filler) | 90 |
| Hydroxypropyl methylcellulose (binding agent) | 25 |
| Carboxymethylstach sodium (disintegrating agent) | 30 |
| Pulvis Talci (profit adds up to) | 3 |
| Element tablet weight | 348 |
The preparation technology of pharmaceutical composition X6:
(1) dexibuprofen is pulverized, cross 100 mesh sieves；Portions microcrystalline cellulose pulverized 80 mesh sieves；The two is put three-dimensional mixed
Conjunction machine mixes 15 minutes, makes mixed powder.
(2) preparing the hydroxypropyl methylcellulose solution of 4% concentration as a part of binding agent, configuration concentration is the hydroxyl of 2%
A part of binding agent, as another part binding agent, is added in mixed powder, is prepared as soft material, by soft material by the third methocel solution
Be extruded into strip in an extruder, extrusion temperature be less than 40 DEG C, be re-fed in spheronizator cutting, round as a ball, control round as a ball temperature
Less than 40 DEG C, it is eventually fabricated the oval fine pellet core of diameter about 0.5mm.
(3) powder that another part microcrystalline Cellulose is broken into 100 μm puts in another part binding agent, is prepared as
Suspension, does not stop stirring with rotor engagement magnetic stirring apparatus, to ensure uniformly.
(4) fine pellet core is put in fluid bed, blow afloat, with peristaltic pump, suspension is squeezed into fluid bed, with compressed air
Purging atomization, controls temperature of charge and is less than 45 DEG C, and the spray velocity of spraying solvent is 2.5ml/min*cm2, fogging degree be
6.0cm2/ ml, prepared particle diameter is 0.75mm medicated core.
(5) add Pulvis Talci in medicated core periphery and make the pharmaceutical composition containing 2-(-4-isobutyl phenenyl) propanoic acid dextrogyre
X6, with Φ 10mm punch die tabletting.
Testing result:
(1) tablet appearance is good, hardness is good；
(2) disintegration time is 8 minutes, dissolution=96%, RSD=1.1.
Embodiment 7 pharmaceutical composition X7
The prescription of pharmaceutical composition X7:
| Supplementary material | Recipe quantity |
| Dexibuprofen | 200 |
| Microcrystalline Cellulose | 87 |
| Hydroxypropyl methylcellulose | 25 |
| Carboxymethylcellulose calcium | 30 |
| Silicon dioxide | 3 |
| Pulvis Talci | 3 |
| Element tablet weight | 348 |
The preparation technology of pharmaceutical composition X7:
(1) dexibuprofen is pulverized, cross 100 mesh sieves；Carboxymethylcellulose calcium and a part of microcrystalline Cellulose pulverized 80
Mesh sieve；The two is put in three-dimensional mixer and mix 15 minutes, make mixed powder.
(2) preparing the hydroxypropyl methylcellulose solution of 4% concentration as a part of binding agent, configuration concentration is the hydroxyl of 2%
A part of binding agent, as another part binding agent, is added in mixed powder, is prepared as soft material, by soft material by the third methocel solution
Be extruded into strip in an extruder, extrusion temperature be less than 40 DEG C, be re-fed in spheronizator cutting, round as a ball, control round as a ball temperature
Less than 40 DEG C, it is eventually fabricated the oval fine pellet core of diameter about 0.5mm.
(3) powder that another part microcrystalline Cellulose is broken into 120 μm puts in another part binding agent, is prepared as
Suspension, does not stop stirring with rotor engagement magnetic stirring apparatus, to ensure uniformly.
(4) fine pellet core is put in fluid bed, blow afloat, with peristaltic pump, suspension is squeezed into fluid bed, with compressed air
Purging atomization, controls temperature of charge and is less than 45 DEG C, and the spray velocity of spraying solvent is 2.8ml/min*cm2, spray amount be
5.4cm2/ ml, prepared particle diameter is 0.65mm medicated core.
(5) add Pulvis Talci in medicated core periphery and make the pharmaceutical composition containing 2-(-4-isobutyl phenenyl) propanoic acid dextrogyre
X7, with Φ 10mm punch die tabletting.
Testing result:
(1) tablet appearance is good, hardness is good；
(2) disintegration time is 8 minutes, dissolution=97%, RSD=0.9.
In sum, the pharmaceutical composition containing 2-(-4-isobutyl phenenyl) propanoic acid dextrogyre of the present invention has following excellent
Point:
(1) use relatively little of dosage i.e. to can reach the curative effect of ibuprofen, and reduce ibuprofen levorotatory side effect
Risk；
(2) by disintegrating agent, binding agent and the rational proportion of filler, 2-(-4-isobutyl phenenyl) propanoic acid is masked
Other abnormal flavour after the bitterness of dextrogyre and entrance thereof, improve patient medication compliance, reach more preferably to cure the effect of illness
Really..
(3) by new production thinking, new technology, improve the result of extraction of principal agent and reached the mesh of homogeneous release
's.
Descriptions above can combine enforcement individually or in every way, and these variant all exist
Within protection scope of the present invention.
It should be noted that in this article, term " includes ", " comprising " or its any other variant are intended to non-row
Comprising of his property, so that include that the article of a series of key element or equipment not only include those key elements, but also include not
There are other key elements being expressly recited, or also include the key element intrinsic for this article or equipment.There is no more limit
In the case of system, statement " including ... " key element limited, it is not excluded that in the article including described key element or equipment
There is also other identical element.
Above example is only in order to illustrate technical scheme and unrestricted, reference only to preferred embodiment to this
Bright it is described in detail.It will be understood by those within the art that, technical scheme can be modified
Or equivalent, without deviating from the spirit and scope of technical solution of the present invention, all should contain the claim model in the present invention
In the middle of enclosing.
Claims (10)
1. the pharmaceutical composition containing 2-(-4-isobutyl phenenyl) propanoic acid dextrogyre, it is characterised in that described pharmaceutical composition
Composition and content be:
2-(-4-isobutyl phenenyl) propanoic acid dextrogyre 30～80wt%；
Disintegrating agent 1～25wt%.
2. pharmaceutical composition as claimed in claim 1, it is characterised in that described pharmaceutical composition also includes:
Binding agent 1～10wt%；
Filler 20～60wt%.
3. pharmaceutical composition as claimed in claim 1, it is characterised in that
Described disintegrating agent includes in polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, carboxymethylcellulose calcium, carboxymethylstach sodium
One or more, the most preferably one or both in carboxymethylcellulose calcium, cross-linking sodium carboxymethyl cellulose.
4. pharmaceutical composition as claimed in claim 2, it is characterised in that
Described binding agent includes the one in hydroxypropyl methylcellulose, hydroxypropyl cellulose, polyvidone, corn starch or water or several
Kind, the most preferably hydroxypropyl methylcellulose；
Described filler includes one or more in microcrystalline Cellulose, corn starch, calcium phosphate.
5. the preparation method of pharmaceutical composition as described in any one in claim 2～4, it is characterised in that include
Following steps:
(1) by described 2-(-4-isobutyl phenenyl) propanoic acid dextrogyre and described disintegrating agent micronization respectively, and it is dry mixed and is formed uniformly
Mixed powder, the particle diameter controlling described 2-(-4-isobutyl phenenyl) propanoic acid dextrogyre micropowder is 120～180 μm, controls described disintegrating agent
The particle diameter of micropowder is less than or equal to 180 μm so that the composition of mixed powder is full and uniform；
(2) in described mixed powder, add a part of binding agent and make fine pellet core, control the particle diameter of described fine pellet core be 0.1～
0.7mm, preferably 0.3～0.5mm；
(3) by a part of filler micronization, and mix to uniformly with another part binding agent, make spraying solvent；
(4) use the mode of bed spray, described spraying solvent is homogeneously applied to the surface of fine pellet core, makes medicine
Core.
6. the preparation method of pharmaceutical composition as claimed in claim 5, it is characterised in that described step (4) including:
Use peristaltic pump that described spraying solvent is sent into fluid bed, make it be atomized by the way of compressed air purges, use top
Spray or the method for end spray, be sprayed at the surface of described fine pellet core equably by described spraying solvent, and drying prepares described medicine
Core, wherein, the spray velocity of described spraying solvent is 2.5～3.5mL/min*cm2, spray amount is 4～6cm2/mL。
7. the preparation method of pharmaceutical composition as claimed in claim 5, it is characterised in that described step (3) including:
The particle diameter controlling filler micropowder is 80～120 μm, preferably 95～105 μm.
8. the preparation method of pharmaceutical composition as claimed in claim 5, it is characterised in that described step (1) including:
Another part filler is micronized to particle diameter and is less than or equal to 180 μm, by micronized 2-(-4-isobutyl phenenyl) propanoic acid
Dextrogyre, disintegrating agent and another part filler are dry mixed the mixed powder of formation so that mixed powder is full and uniform.
9. the preparation method of pharmaceutical composition as claimed in claim 5, it is characterised in that described step (4) including:
Controlling the temperature of fine pellet core in fluid bed is 40～46 DEG C, preferably 43～45 DEG C；
Described step (2) including:
In described mixed powder, add a part of binding agent make soft material, and make fine pellet core by extrusion and spheronization step, control
Temperature and the round as a ball temperature of system extrusion are 30～45 DEG C, are preferably all 39～42 DEG C.
10. the preparation method of pharmaceutical composition as claimed in claim 5, it is characterised in that described preparation method also includes position
Step after described step (4):
(5) add lubricant in medicated core periphery, form described pharmaceutical composition.
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|---|---|---|---|
| CN201610189107.4A CN105935445B (en) | 2016-03-28 | 2016-03-28 | Pharmaceutical composition and preparation method thereof containing 2- (- 4- isobutyl phenenyl) propionic acid dextrogyre |
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