CN105935445B - Pharmaceutical composition and preparation method thereof containing 2- (- 4- isobutyl phenenyl) propionic acid dextrogyre - Google Patents

Pharmaceutical composition and preparation method thereof containing 2- (- 4- isobutyl phenenyl) propionic acid dextrogyre Download PDF

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CN105935445B
CN105935445B CN201610189107.4A CN201610189107A CN105935445B CN 105935445 B CN105935445 B CN 105935445B CN 201610189107 A CN201610189107 A CN 201610189107A CN 105935445 B CN105935445 B CN 105935445B
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pharmaceutical composition
dextrogyre
propionic acid
filler
adhesive
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CN105935445A (en
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赵宏伟
张丽华
王艳峰
季丽萍
王洁婷
盛丽
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Chifeng Saliont Pharmaceutical Co Ltd
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Chifeng Saliont Pharmaceutical Co Ltd
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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
    • 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
    • A61K47/30—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
    • 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
    • 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
    • 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
    • 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
    • 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

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Abstract

The invention discloses a kind of pharmaceutical composition and preparation method thereof for containing 2- (- 4- isobutyl phenenyl) propionic acid dextrogyre, the compositions and content of pharmaceutical composition are as follows: 30~80wt% of 2- (- 4- isobutyl phenenyl) propionic acid dextrogyre；1~25wt% of disintegrating agent；Pharmaceutical composition containing 2- (- 4- isobutyl phenenyl) propionic acid dextrogyre of the invention, pass through the rational proportion of disintegrating agent, adhesive and filler, make pharmaceutical composition that there is good absorbent properties and stability, the bitter taste and its other peculiar smell after entrance for masking 2- (- 4- isobutyl phenenyl) propionic acid dextrogyre, patient medication compliance is improved, achievees the effect that more preferably to cure illness.

Description

Pharmaceutical composition and its preparation containing 2- (- 4- isobutyl phenenyl) propionic acid dextrogyre Method
Technical field
The present invention relates to a kind of pharmaceutical compositions and preparation method thereof for containing 2- (- 4- isobutyl phenenyl) propionic acid dextrogyre.
Background technique
2- (- 4- isobutyl phenenyl) propionic acid also known as Ibuprofen, brufen, brufen, with it is anti-inflammatory, analgesia, Refrigeration function.Rheumatism and rheumatoid arthritis can be treated.
Since brufen includes levo form and d-isomer, and according to pertinent literature record the pharmacological activity of brufen mainly come From d-isomer, that is, 2- (- 4- isobutyl phenenyl) propionic acid dextrogyre, levo form does not have pharmacological action, and side effect is unknown, therefore whole A drug effect with brufen pharmaceutical composition as main component is there are room for promotion, and the presence of levo form, also gives It brings that there are the risks of certain side effect.
Summary of the invention
It may be adapted to tabletted or be filled in capsule in order to solve the above-mentioned technical problems, the present invention provides a kind of Pharmaceutical composition and preparation method thereof containing 2- (- 4- isobutyl phenenyl) propionic acid dextrogyre, the pharmaceutical composition is without bitter taste, release Uniformly, good dispersing state belongs to non-steroidal anti-inflammatory drugs, has antipyretic, analgesia and anti-inflammatory effect.
According to an aspect of the invention, there is provided a kind of medicine group for containing 2- (- 4- isobutyl phenenyl) propionic acid dextrogyre Object is closed, following components and constituent content are specifically included:
30~80wt% of 2- (- 4- isobutyl phenenyl) propionic acid dextrogyre；
1~25wt% of disintegrating agent；
Wherein, pharmaceutical composition further include:
1~10wt% of adhesive；
20~60wt% of filler；
Wherein, disintegrating agent includes crospovidone, croscarmellose sodium, calcium carboxymethylcellulose, carboxymethylstarch One or more of sodium, wherein preferably one or both of calcium carboxymethylcellulose, croscarmellose sodium.
Wherein, adhesive includes one in hypromellose, hydroxypropyl cellulose, povidone, cornstarch or water Kind is several, wherein preferably hypromellose；
Filler includes one or more of microcrystalline cellulose, cornstarch, calcium phosphate.
According to another aspect of the present invention, a kind of preparation method of pharmaceutical composition is provided, comprising the following steps:
(1) 2- (- 4- isobutyl phenenyl) propionic acid dextrogyre and disintegrating agent are micronized respectively, and it is dry-mixed be formed uniformly it is mixed Powder, the partial size of control 2- (- 4- isobutyl phenenyl) propionic acid dextrogyre micro mist are 120~180 μm, control the partial size of disintegrating agent micro mist Less than or equal to 180 μm, so that the ingredient of mixed powder is full and uniform；
(2) a part of adhesive being added in mixed powder and fine pellet core is made, the partial size for controlling fine pellet core is 0.1~ 0.7mm, preferably 0.3~0.5mm；
(3) a part of filler is micronized, and mixed with another part adhesive to uniform, spraying solvent is made；
(4) by the way of bed spray, spraying solvent is homogeneously applied to the surface of fine pellet core, medicine is made Core.
Wherein, step (4) includes:
Spraying solvent is sent into fluidized bed using peristaltic pump, its atomization is made by way of compressed air purging, using top Spraying solvent, is equably sprayed at the surface of fine pellet core, medicine core is made in drying by the method for spray or bottom spray, wherein spraying The spray velocity of solvent is 2.5~3.5mL/min*cm2, and spray amount is 4~6cm2/mL.
Wherein, step (3) includes:
The partial size for controlling filler micro mist is 80~120 μm, preferably 95~105 μm.
Wherein, step (1) includes:
Another part filler is micronized to partial size less than or equal to 180 μm, by the 2- (- 4- isobutyl phenenyl) of micronization Propionic acid dextrogyre, disintegrating agent and dry-mixed formed of another part filler mix powder, so that mixed powder is full and uniform.
Wherein, it is 40~46 DEG C, preferably 43~45 DEG C that step (4), which includes: the temperature of fine pellet core in control fluidized bed,；
Step (2) includes: a part of adhesive to be added in mixed powder softwood is made, and be made by squeezing out with spheronization step Fine pellet core, the temperature and round as a ball temperature for controlling extrusion are 30~45 DEG C, are preferably all 39~42 DEG C.
Wherein, preparation method further includes the steps that being located at after step (4): lubricant is added in medicine core periphery in (5), is formed Pharmaceutical composition.
Wherein, disintegrating agent discharges main ingredient, disintegrating agent is too low, and pharmaceutical composition can not be real for being disintegrated pharmaceutical composition Now sufficiently disintegration, influences the dissolution and absorption of main component, and disintegrating agent is excessively high, is easy to produce aggregation, mixes unevenness, will affect particle Mobility so that drug granule weight differential is big, and disintegrating agent excessively be easy to cause pharmaceutical composition to be easy moisture absorption, to storage It deposits and causes difficulty, influence the stability of pharmaceutical composition.In the present invention, it is suitable for 2- (- 4- isobutyl phenenyl) propionic acid dextrogyre Disintegrating agent include one of crospovidone, croscarmellose sodium, calcium carboxymethylcellulose, carboxyrnethyl starch sodium or It is several.And in the present invention, when the content of disintegrating agent is 1~25wt%, this contains 2- (- 4- isobutyl phenenyl) propionic acid dextrogyre The dissolution of pharmaceutical composition, absorption, stability are best.
Adhesive mainly plays bonding and wetting, soaks dry-mixed main ingredient and auxiliary material and is made suitable Softwood, make it suitable for it is round as a ball, on the other hand can make filler be adhered to it is round as a ball after the surface of fine pellet core reach taste masking, Protect the effect of drug capsule core.In the present invention, the adhesive for being suitable for 2- (- 4- isobutyl phenenyl) propionic acid dextrogyre includes hydroxypropyl One or more of methylcellulose, hydroxypropyl cellulose, povidone, cornstarch or water.And in the present invention, adhesive Content be between 1~10wt% it is suitable, can be easy with pelletizing forming, and the density that makes to pelletize is optimal.
Filler is to prepare excipient added by solid pharmaceutical preparation, is mainly worked in molding, also known as diluent, is applied It covers and is mainly used for removing the bitter taste of 2- (- 4- isobutyl phenenyl) propionic acid dextrogyre with the surface of fine pellet core, due to the increasing of drug It is important have clearly control, to control the divided dose of formation solid preparation, under normal conditions be added filler after weight gain range exist Between 5-25%, therefore the weight of filler is different according to the specification of types of drugs and the difference of the ingredient of weighting agent, this In invention, the Suitable ingredients content of filler is 20~60wt%.
During practical pharmacy, in tablet press or capsule charge, in order to guarantee slice weight or charging quantity, also need to add Add the pulverulent solids that can guarantee medicine core proper flow, i.e. lubricant.In the present invention, the suitable additive amount of lubricant is medicine Between the 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) propionic acid dextrogyre and disintegrating agent dosage summation 0.5~10%.
In addition, the homogeneity of main ingredient ingredient release is to influence the key factor of drug effect in pharmaceutical technology, containing 2-, (- 4- is different Butyl phenyl) propionic acid dextrogyre pharmaceutical composition preparation method in, disintegrating agent and main ingredient ingredient 2- (- 4- in dry mixing step Isobutyl phenenyl) propionic acid dextrogyre whether mixing uniform and the partial size of manufactured fine pellet core is the pass for influencing homogeneity Key.
In actual pharmacy procedure, whether disintegrating agent and main ingredient ingredient mix and are often difficult to judge, inventor passes through big The experiment of amount and data comparison discovery, are crushed to 120~180 μm for main ingredient ingredient, disintegrating agent is crushed to less than 180 μm, then is taken It is operated with conventional mixing, can achieve sufficient mixed effect.
In addition, the spray effect of bed spray process is also another key factor for influencing homogeneity, and fine pellet core Size it is directly related with spray effect, fine pellet core is too small, spray not uniform enough, the coated uniformity of filler, pellet ball Core is excessive, and it is more difficult that fluidized bed is blown afloat, and coating effect is equally bad.In the present invention, between 0.1~0.7mm of fine pellet core, preferably Between 0.3~0.5mm, it can guarantee being uniformly distributed for each ingredient of pharmaceutical composition.
The spray effect of bed spray process also with the direct phase of the degree of the mode of atomization, the speed of atomization and atomization It closes, while in view of the fusing point of 2- (- 4- isobutyl phenenyl) propionic acid dextrogyre as primary raw material only has 48~52 DEG C, therefore Strict temperature control is answered in operations, during using fluidized bed, strict temperature control to be no more than 45 DEG C, because This, dosage spraying in the present invention, speed, fogging degree need to be adapted with the temperature of charge of fluidized bed, are guaranteeing main ingredient It is infusible under the premise of, guarantee that the attachment of filler is uniform, it is dry rapidly.
In addition, the partial size of filler micro mist is also an important factor for influencing atomizing effect in spraying solvent.By strictly controlling These pharmacy parameters are made, the present invention is by the control to process above parameter, so that last pharmaceutical composition obtained reaches equal The effect of one release.
Pharmaceutical composition containing 2- (- 4- isobutyl phenenyl) propionic acid dextrogyre of the invention has the advantage that
(1) it is the curative effect that can reach brufen using relatively little of dosage, and reduces brufen levorotatory side effect Risk；
(2) rational proportion for passing through disintegrating agent, adhesive and filler, makes pharmaceutical composition have good absorbability Energy and stability, the bitter taste and its other peculiar smell after entrance for masking 2- (- 4- isobutyl phenenyl) propionic acid dextrogyre improve Patient medication compliance achievees the effect that more preferably to cure illness.
(3) it by new production thinking, new process, improves the result of extraction of main ingredient and has reached the mesh of uniform release 's.
Specific embodiment
In order to make the object, technical scheme and advantages of the embodiment of the invention clearer, to the technology in the embodiment of the present invention Scheme is clearly and completely described, it is clear that and described embodiments are some of the embodiments of the present invention, rather than whole Embodiment.Based on the embodiments of the present invention, those of ordinary skill in the art are obtained without making creative work The every other embodiment obtained, shall fall within the protection scope of the present invention.It should be noted that in the absence of conflict, this Shen Please in embodiment and embodiment in feature can mutual any combination.
1 pharmaceutical composition X1 of embodiment
The prescription of pharmaceutical composition X1:
Supplementary material Recipe quantity (mg)
Dexibuprofen 75
Microcrystalline cellulose (another part filler) 138
Hypromellose (adhesive) 19.5
Croscarmellose sodium (disintegrating agent) 2.5
Calcium phosphate (a part of filler) 12
Magnesium stearate (lubricant) 3
Plain piece weight 250
The preparation process of pharmaceutical composition X1:
(1) Dexibuprofen is ground into 150 μm, sieved with 100 mesh sieve；By croscarmellose sodium, microcrystal cellulose powder About 180 μm are broken into, 80 meshes are crossed；Three is set in three-dimensional mixer and is mixed 15 minutes, mixed powder is made.
(2) the hypromellose solution of 1% concentration is prepared as adhesive, and a part therein is added to mixed powder In, be prepared into softwood, softwood be extruded into strip in an extruder, extrusion temperature is 45 DEG C, be re-fed into cutting in spheronizator, It is round as a ball, round as a ball temperature is controlled between 30~45 DEG C, is eventually fabricated the oval fine pellet core of diameter about 0.1mm.
(3) powder that microcrystalline cellulose is broken into 80 μm is put into another part adhesive, is prepared into suspension, to turn Son cooperation magnetic stirring apparatus is kept stirring, uniform to guarantee.
(4) fine pellet core is put into fluidized bed, blows afloat, suspension is squeezed by fluidized bed with peristaltic pump, with compressed air The surface for being also homogeneously applied to fine pellet core that is suspended is made the medicine core that partial size is 0.15mm, controls pellet ball by purging atomization For the temperature of core between 43~45 DEG C, the spray velocity of spraying solvent is 2.5ml/min*cm2, spray amount 4.0cm2/ml。
(5) magnesium stearate is added in medicine core periphery and the pharmaceutical composition containing 2- (- 4- isobutyl phenenyl) propionic acid dextrogyre is made Object X1, with Φ 10mm punch die tabletting.
Testing result:
(1) tablet appearance is good, hardness is good；
(2) disintegration time is 13 minutes, dissolution rate=88%, RSD=1.5.
2 pharmaceutical composition X2 of embodiment
The prescription of pharmaceutical composition X2:
Supplementary material Recipe quantity (mg)
Dexibuprofen 420
Hydroxypropyl cellulose (adhesive) 65
Croscarmellose sodium (disintegrating agent) 6.5
Cornstarch (filler) 117
Magnesium stearate (lubricant) 41.5
Plain piece weight 650
The preparation process of pharmaceutical composition X2:
(1) Dexibuprofen is ground into 120 μm, crosses 120 meshes；Croscarmellose sodium is ground into 170 μm, mistake 80 meshes；The two is set in three-dimensional mixer and is mixed 15 minutes, mixed powder is made.
(2) hydroxypropyl cellulose solution of 4% concentration is prepared as adhesive, and a part therein is added to mixed powder In, it is prepared into softwood, softwood is extruded into strip in an extruder, extrusion temperature is located at 39~42 DEG C, is re-fed into spheronizator It is middle to cut, is round as a ball, round as a ball temperature is controlled positioned at 39~42 DEG C, is eventually fabricated the oval fine pellet core of diameter about 0.7mm.
(3) powder that microcrystalline cellulose is broken into 80 μm is put into another part adhesive, is prepared into suspension, to turn Son cooperation magnetic stirring apparatus is kept stirring, uniform to guarantee.
(4) fine pellet core is put into fluidized bed, blows afloat, suspension is squeezed by fluidized bed with peristaltic pump, with compressed air Purging atomization, the temperature for controlling fine pellet core are located at 40~46 DEG C, and the spray velocity of spraying solvent is 3ml/min*cm2, it is spraying Amount is 4.8cm2The medicine core that partial size is 0.9mm is made in/ml.
(5) magnesium stearate is added in medicine core periphery and the pharmaceutical composition containing 2- (- 4- isobutyl phenenyl) propionic acid dextrogyre is made Object X2, with Φ 10mm punch die tabletting.
Testing result:
(1) tablet appearance is good, hardness is good；
(2) disintegration time is 8 minutes, dissolution rate=95%, RSD=1.1.
3 pharmaceutical composition X3 of embodiment
The prescription of pharmaceutical composition X3:
Supplementary material Recipe quantity (mg)
Dexibuprofen 200
Calcium phosphate (filler) 87
Povidone (adhesive) 16
Carboxyrnethyl starch sodium (disintegrating agent) 22
Silica (lubricant) 20
Talcum powder (lubricant) 3
Plain piece weight 348
The preparation process of pharmaceutical composition X3:
(1) Dexibuprofen is ground into 180 μm, crosses 80 meshes；Carboxyrnethyl starch sodium is ground into 150 μm, sieves with 100 mesh sieve；It will The two is set in three-dimensional mixer and is mixed 15 minutes, and mixed powder is made.
(2) povidone solution of 1% concentration is prepared as adhesive, a part therein is added into mixed powder, preparation At softwood, softwood is extruded into strip in an extruder, extrusion temperature is 40 DEG C, is re-fed into cutting in spheronizator, 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 is put into another part adhesive, is prepared into suspension, matched with rotor Magnetic stirring apparatus is closed to keep stirring, it is uniform to guarantee.
(4) fine pellet core is put into fluidized bed, blows afloat, suspension is squeezed by fluidized bed with peristaltic pump, with compressed air Purging atomization, control temperature of charge are 44 DEG C, and the spray velocity of spraying solvent is 3.5ml/min*cm2, atomization quantity 5.0cm2/ The medicine core that partial size is 0.45mm is made in ml.
(5) silica is added in medicine core periphery and talcum powder is made containing 2- (- 4- isobutyl phenenyl) propionic 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 rate=98%, RSD=0.8.
4 pharmaceutical composition X4 of embodiment
The prescription of pharmaceutical composition X4:
Supplementary material Recipe quantity (mg)
Dexibuprofen 100
Cornstarch (filler) 154.52
Water (adhesive) 3.48
Carboxyrnethyl starch sodium (disintegrating agent) 87
Silica (lubricant) 3
Plain piece weight 348
The preparation process of pharmaceutical composition X4:
(1) Dexibuprofen is ground into 180 μm, crosses 80 meshes；Carboxyrnethyl starch sodium, cornstarch are ground into 150 μm, mistake 100 meshes；Three is set in three-dimensional mixer and is mixed 15 minutes, mixed powder is made.
(2) the calcium carboxymethylcellulose solution of 4% concentration is prepared as adhesive, and a part therein is added to mixed powder In, it is prepared into softwood, softwood is extruded into strip in an extruder, extrusion temperature is lower than 40 DEG C, is re-fed into spheronizator and cuts It cuts, is round as a ball, controlling round as a ball temperature lower 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 is put into another part adhesive, is prepared into suspension, with Rotor engagement magnetic stirring apparatus is kept stirring, uniform to guarantee.
(4) fine pellet core is put into fluidized bed, blows afloat, suspension is squeezed by fluidized bed with peristaltic pump, with compressed air Purging atomization, control temperature of charge are lower than 40 DEG C, and the spray velocity of spraying solvent is 2.9ml/min*cm2, spray amount 6cm2/ Ml, it is 0.75mm medicine core that partial size, which is made,.
(5) silica is added in medicine core periphery and the pharmaceutical composition containing 2- (- 4- isobutyl phenenyl) propionic acid dextrogyre is made Object X4, with Φ 10mm punch die tabletting.
(1) tablet appearance is good, hardness is good；
(2) disintegration time is 3 minutes, dissolution rate=97%, RSD=0.7.
5 pharmaceutical composition X5 of embodiment
The prescription of pharmaceutical composition X5:
Supplementary material Recipe quantity
Dexibuprofen 200
Microcrystalline cellulose (filler) 80
Hypromellose (adhesive) 20
Carboxyrnethyl starch sodium (disintegrating agent) 25
Cornstarch (filler) 20
Magnesium stearate (lubricant) 3
Plain piece weight 348
The preparation process of pharmaceutical composition X5:
(1) Dexibuprofen is crushed, is sieved with 100 mesh sieve；Carboxyrnethyl starch sodium, cornstarch crushed 80 meshes；Three is set It is mixed 15 minutes in three-dimensional mixer, mixed powder is made.
(2) the hypromellose solution of 4% concentration is prepared as adhesive, and a portion is added in mixed powder, Be prepared into softwood, softwood be extruded into strip in an extruder, extrusion temperature is lower than 40 DEG C, be re-fed into cutting in spheronizator, It is round as a ball, round as a ball temperature is controlled lower than 40 DEG C, is eventually fabricated the oval fine pellet core of diameter about 0.5mm.
(3) powder that microcrystalline cellulose is broken into 100 μm is put into another part adhesive, is prepared into suspension, with Rotor engagement magnetic stirring apparatus is kept stirring, uniform to guarantee.
(4) fine pellet core is put into fluidized bed, blows afloat, suspension is squeezed by fluidized bed with peristaltic pump, with compressed air Purging atomization, control temperature of charge are lower than 45 DEG C, atomization speed 3.5ml/min*cm2, fogging degree 5.6cm2/ ml is made Partial size is 0.8mm medicine core.
(5) silica is added in medicine core periphery and the pharmaceutical composition containing 2- (- 4- isobutyl phenenyl) propionic acid dextrogyre is made Object X5, with Φ 10mm punch die tabletting.
Testing result:
(1) tablet appearance is good, hardness is good；
(2) disintegration time is 13 minutes, dissolution rate=87%, RSD=1.4.
6 pharmaceutical composition X6 of embodiment
The prescription of pharmaceutical composition X6:
Supplementary material Recipe quantity
Dexibuprofen 200
Microcrystalline cellulose (filler) 90
Hypromellose (adhesive) 25
Carboxyrnethyl starch sodium (disintegrating agent) 30
Talcum powder (profit is total) 3
Plain piece weight 348
The preparation process of pharmaceutical composition X6:
(1) Dexibuprofen is crushed, is sieved with 100 mesh sieve；Portions microcrystalline cellulose crushed 80 meshes；The two is set three-dimensional mixed It is mixed 15 minutes in conjunction machine, mixed powder is made.
(2) the hypromellose solution of 4% concentration of preparation is as a part of adhesive, the hydroxyl that configuration concentration is 2% A part of adhesive is added in mixed powder as another part adhesive, softwood is prepared into, by softwood by the third methocel solution It is extruded into strip in an extruder, extrusion temperature is lower than 40 DEG C, is re-fed into spheronizator and cuts, is round as a ball, controls round as a ball temperature Lower 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 is put into another part adhesive, is prepared into mixed Suspension is kept stirring with rotor engagement magnetic stirring apparatus, uniform to guarantee.
(4) fine pellet core is put into fluidized bed, blows afloat, suspension is squeezed by fluidized bed with peristaltic pump, with compressed air Purging atomization, control temperature of charge are lower than 45 DEG C, and the spray velocity of spraying solvent is 2.5ml/min*cm2, fogging degree be 6.0cm2/ ml, it is 0.75mm medicine core that partial size, which is made,.
(5) talcum powder is added in medicine core periphery and the pharmaceutical composition containing 2- (- 4- isobutyl phenenyl) propionic acid dextrogyre is made X6, with Φ 10mm punch die tabletting.
Testing result:
(1) tablet appearance is good, hardness is good；
(2) disintegration time is 8 minutes, dissolution rate=96%, RSD=1.1.
7 pharmaceutical composition X7 of embodiment
The prescription of pharmaceutical composition X7:
Supplementary material Recipe quantity
Dexibuprofen 200
Microcrystalline cellulose 87
Hypromellose 25
Calcium carboxymethylcellulose 30
Silica 3
Talcum powder 3
Plain piece weight 348
The preparation process of pharmaceutical composition X7:
(1) Dexibuprofen is crushed, is sieved with 100 mesh sieve；Calcium carboxymethylcellulose and a part of microcrystalline cellulose crushed 80 Mesh；The two is set in three-dimensional mixer and is mixed 15 minutes, mixed powder is made.
(2) the hypromellose solution of 4% concentration of preparation is as a part of adhesive, the hydroxyl that configuration concentration is 2% A part of adhesive is added in mixed powder as another part adhesive, softwood is prepared into, by softwood by the third methocel solution It is extruded into strip in an extruder, extrusion temperature is lower than 40 DEG C, is re-fed into spheronizator and cuts, is round as a ball, controls round as a ball temperature Lower 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 is put into another part adhesive, is prepared into mixed Suspension is kept stirring with rotor engagement magnetic stirring apparatus, uniform to guarantee.
(4) fine pellet core is put into fluidized bed, blows afloat, suspension is squeezed by fluidized bed with peristaltic pump, with compressed air Purging atomization, control temperature of charge are lower than 45 DEG C, and the spray velocity of spraying solvent is 2.8ml/min*cm2, spray amount be 5.4cm2/ ml, it is 0.65mm medicine core that partial size, which is made,.
(5) talcum powder is added in medicine core periphery and the pharmaceutical composition containing 2- (- 4- isobutyl phenenyl) propionic acid dextrogyre is made X7, with Φ 10mm punch die tabletting.
Testing result:
(1) tablet appearance is good, hardness is good；
(2) disintegration time is 8 minutes, dissolution rate=97%, RSD=0.9.
In conclusion the pharmaceutical composition containing 2- (- 4- isobutyl phenenyl) propionic acid dextrogyre of the invention is with following excellent Point:
(1) it is the curative effect that can reach brufen using relatively little of dosage, and reduces brufen levorotatory side effect Risk；
(2) rational proportion for passing through disintegrating agent, adhesive and filler, masks 2- (- 4- isobutyl phenenyl) propionic acid The bitter taste of dextrogyre and its other peculiar smell after entrance, improve patient medication compliance, reach the more preferable effect for curing illness Fruit.
(3) it by new production thinking, new process, improves the result of extraction of main ingredient and has reached the mesh of uniform release 's.
Descriptions above can combine implementation individually or in various ways, and these variants all exist Within protection scope of the present invention.
It should be noted that, in this document, the terms "include", "comprise" or its any other variant are intended to non-row His property includes, so that including the article of a series of elements or equipment not only includes those elements, but also including not having There is the other element being expressly recited, or further includes for this article or the intrinsic element of equipment.Do not limiting more In the case where system, the element that is limited by sentence " including ... ", it is not excluded that in the article or equipment for including the element There is also other identical elements.
The above examples are only used to illustrate the technical scheme of the present invention and are not limiting, reference only to preferred embodiment to this hair It is bright to be described in detail.Those skilled in the art should understand that can modify to technical solution of the present invention Or equivalent replacement should all cover in claim model of the invention without departing from the spirit and scope of the technical solution of the present invention In enclosing.

Claims (11)

1. the pharmaceutical composition that one kind contains 2- (- 4- isobutyl phenenyl) propionic acid dextrogyre, which is characterized in that described pharmaceutical composition Composition and content are as follows:
The preparation method of described pharmaceutical composition, comprising the following steps:
(1) 2- (- 4- isobutyl phenenyl) propionic acid dextrogyre and the disintegrating agent are micronized respectively, and dry-mixed are formed uniformly Mixed powder, the partial size for controlling the 2- (- 4- isobutyl phenenyl) propionic acid dextrogyre micro mist is 120~180 μm, controls the disintegrating agent The partial size of micro mist is less than or equal to 180 μm, so that the ingredient of mixed powder is full and uniform；
(2) a part of adhesive is added in the mixed powder and fine pellet core is made, control the fine pellet core partial size be 0.1~ 0.7mm；
(3) a part of filler is micronized, and mixed with another part adhesive to uniform, spraying solvent is made；
(4) by the way of bed spray, the spraying solvent is homogeneously applied to the surface of fine pellet core, medicine is made Core；
(5) lubricant is added in medicine core periphery, forms described pharmaceutical composition；
The disintegrating agent include crospovidone, croscarmellose sodium, calcium carboxymethylcellulose, in carboxyrnethyl starch sodium It is one or more of；
Described adhesive includes one or more of hypromellose, hydroxypropyl cellulose, povidone, cornstarch；
The filler includes one or more of microcrystalline cellulose, cornstarch, calcium phosphate.
2. pharmaceutical composition as described in claim 1, which is characterized in that
The disintegrating agent is one or both of calcium carboxymethylcellulose, croscarmellose sodium.
3. pharmaceutical composition as described in claim 1, which is characterized in that described adhesive is hypromellose.
4. pharmaceutical composition as described in claim 1, which is characterized in that the partial size of fine pellet core is 0.3 in the step (2) ~0.5mm.
5. pharmaceutical composition as described in claim 1, which is characterized in that the step (4) includes:
The spraying solvent is sent into fluidized bed using peristaltic pump, its atomization is made by way of compressed air purging, using top The spraying solvent, is equably sprayed at the surface of the fine pellet core by the method for spray or bottom spray, and the medicine is made in drying Core, wherein the spray velocity of the spraying solvent is 2.5~3.5mL/min*cm2, spray amount is 4~6cm2/mL。
6. pharmaceutical composition as described in claim 1, which is characterized in that the step (3) includes:
The partial size for controlling filler micro mist is 80~120 μm.
7. pharmaceutical composition as claimed in claim 6, which is characterized in that it is described control filler micro mist partial size be 95~ 105μm。
8. pharmaceutical composition as described in claim 1, which is characterized in that the step (1) includes:
Another part filler is micronized to partial size less than or equal to 180 μm, by 2- (- 4- isobutyl phenenyl) propionic acid of micronization Dextrogyre, disintegrating agent and dry-mixed formed of another part filler mix powder, so that mixed powder is full and uniform.
9. pharmaceutical composition as described in claim 1, which is characterized in that the step (4) includes:
The temperature for controlling fine pellet core in fluidized bed is 40~46 DEG C；
The step (2) includes:
A part of adhesive is added in the mixed powder, softwood is made, and fine pellet core is made with spheronization step by squeezing out, controls It makes the temperature squeezed out and round as a ball temperature is 30~45 DEG C.
10. pharmaceutical composition as claimed in claim 9, which is characterized in that the temperature of fine pellet core in the control fluidized bed It is 43~45 DEG C.
11. pharmaceutical composition as claimed in claim 9, which is characterized in that the temperature and round as a ball temperature that the control squeezes out It is 39~42 DEG C.
CN201610189107.4A 2016-03-28 2016-03-28 Pharmaceutical composition and preparation method thereof containing 2- (- 4- isobutyl phenenyl) propionic acid dextrogyre Active CN105935445B (en)

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