CN105395494A - Medicine composition containing succinic acid solifenacin and preparation method of medicine composition - Google Patents
Medicine composition containing succinic acid solifenacin and preparation method of medicine composition Download PDFInfo
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- CN105395494A CN105395494A CN201510851876.1A CN201510851876A CN105395494A CN 105395494 A CN105395494 A CN 105395494A CN 201510851876 A CN201510851876 A CN 201510851876A CN 105395494 A CN105395494 A CN 105395494A
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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
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/49—Cinchonan derivatives, e.g. quinine
-
- 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
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- 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
- A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
-
- 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
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
Abstract
The invention relates to a composition containing succinic acid solifenacin. A direct powder compression method is adopted, the technical problems such as instable dampness and heat of succinic acid solifenacin during wet granulation are solved, the grain diameter of active ingredients is controlled, a mixing technique of premixing, dispersing and total mixing is adopted, mixing uniformity of bulk drugs in the composition is guaranteed, and therefore it is guaranteed that the content uniformity of finished products meets requirements. The composition containing succinic acid solifenacin is stable in quality, low in cost and very suitable for industrial production, and production process operation is easy.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, specifically, relate to pharmaceutical composition of a kind of succinic acid YM-905 and preparation method thereof.
Background technology
Succinic acid YM-905 chemistry (3R)-1-azabicyclo [2.2.2] oct-3-yl (1S)-1-phenyl-3,4-dihydro-isoquinoline-2 (1H)-carboxylate monosuccinic acid salt by name.
It is reported, the a series of quinuclidine derivatives comprising solifenacin or its salt have splendid selection antagonism to muscarine M3 receptor, and can be used as urinary disorders such as nerve frequent micturition, neurogenic bladder, nocturia, unstable bladder, contracture of bladder and chronic cystitis and respiratory disorder, the preventive of such as chronic obstructive pulmonary disease, chronic bronchitis, asthma and rhinitis or therapeutic agent.
Succinic acid YM-905 grinds exploitation by Japanese Yamanouchi drugmaker is former, now sold by Japanese Astellas pharmaceutical manufacturing, in August, 2004, succinic acid YM-905 sheet was first in Europe listing, obtained FDA license in November, 2004, the granted listing of in JIUYUE, 2009 China's import, trade name defends happiness health (Vesicare), tablet, 5mg, 10mg, daily once, China only goes on the market 5mg sheet, and Astellas pharmacy in 2011 have been gone on the market YM-905 oral cavity disintegration tablet in Japan, trade name VesicareOD.
The preparation method of tablet generally can be divided into granulating tabletting process and direct compression process, granulating tabletting process is the most frequently used is wet granulation, after the powder mix homogeneously by medicine and adjuvant, add the method that liquid adhesive prepares granule, the method has the advantages such as particle appearance is attractive in appearance, good fluidity, mixing uniformity are good, compressibility is good, but for thermo-responsive, the material such as wet sensitive sense, very easily dissolubility is improper.Direct powder compression directly the mixture of medicine and adjuvant is carried out tabletting without pelletization, have time-saving energy-saving, simple process, operation few, be applicable to the outstanding advantages such as wet heat-labile medicine, but also there is the problem of the aspects such as powder flowbility, compressibility, mixing uniformity.
Succinic acid YM-905 sheet specification is little, is 5mg, there is the problem of mixing difficulty; Patent CN200580009495.3 points out that succinic acid YM-905 has stronger aggregation, and as adopted direct compression process, be difficult to the uniformity ensureing content, therefore succinic acid YM-905 sheet is not suitable for producing with direct compression process.And adopt wet granulation, the unformed succinic acid YM-905 that succinic acid YM-905 can produce in the fabrication process, cause active component As time goes on to degrade.Patent CN200580009495.3 is the solifenacin compositions patent of Yuan Yan manufacturer application, adopts wet granulation, with the addition of PEG and change inhibitor as crystal formation, suppress the succinic acid YM-905 of crystal formation in wet granulation is crossed to unformed conversion.But PEG is high-hydrophilic material, hygroscopicity is strong, easily causes product moisture absorption, thus may affect the stability of medicine in preparation process and storage.
Therefore, provide a kind of simple, safety, stay-in-grade succinic acid Suo Lina sheet new recipe, technique is very necessary.
Summary of the invention
The object of the invention is to overcome in direct compression process process, because succinic acid YM-905 has stronger aggregation and the little and technological deficiency of the problem such as cause uniformity of dosage units defective of specification, there is provided a kind of stable, simple to operate, with low cost, efficient preparation technology, with applicable industrialized great production.
The invention provides a kind of pharmaceutical composition containing succinic acid YM-905, by weight, comprising:
Succinic acid YM-905: 1 part;
Diluent: 20-30 part, preferably 25 parts;
Binding agent: 2-6 part, preferably 4 parts;
Lubricant: 0-0.4 part, preferably 0.2 part;
Wherein said compositions is tablet;
The employing direct compression process preparation of wherein said compositions.
The D0.9 of wherein said succinic acid YM-905 is 10-200 μm, preferred 10-150 μm, most preferably 10-100 μm.
The present inventor finds, succinic acid YM-905 is along with the reduction of particle diameter, and mixing homogeneity can improve, and particularly when particle diameter D0.9 is about 80 μm, mixing uniformity is very good; And when particle diameter D0.9 is at about 25 μm, mixing uniformity does not further promote.Usually when D0.9 is less than 10 μm, need to adopt micromill process, technical process is more complicated, and electrostatic force becomes large, aggregate themselves is had to be inclined to, be unfavorable for mix homogeneously, therefore control crude drug particle diameter D0.9 and control the technological deficiency that both can well solve the uniformity between 10-200 μm, be beneficial to again technique in industry and simplify and cost control.
Wherein, D refers to a grain diameter, and the particle that namely D0.9 value tests in sample 90% is in below this numerical value.Data of the present invention all measure with M2000 Malvern laser particle size analyzer and obtain.
Wherein said diluent is lactose, starch, starch lactose, dextrin, microcrystalline Cellulose, one or more in mannitol, preferred starch lactose.
Wherein said binding agent is hydroxypropyl methylcellulose, hydroxypropyl cellulose, polyvinylpyrrolidone, preferred hydroxypropyl methylcellulose.
Wherein said lubricant is stearic acid, magnesium stearate, calcium stearate, rich horse sodium stearate, preferred magnesium stearate.
Present invention also offers a kind of method preparing pharmaceutical composition as claimed in claim 1, comprising:
1) succinic acid YM-905 particle diameter, is controlled;
2), succinic acid YM-905 and binding agent premix disperse afterwards and filler premix disperseing, more always to mix with lubricant;
3), conventional method tabletting.
The particle diameter D0.9 of wherein said succinic acid YM-905 is 10-200 μm, preferred 10-150 μm, most preferably 10-100 μm.
Wherein said step 2) be:
Premix 1: succinic acid YM-905 and binding agent are carried out premix in Mixers with Multi-direction Movement, then adds in crushing and pelletizing machine dispersion of sieving, crushing and pelletizing machine adopts 1.0mm aperture screen cloth;
Premix 2: add diluent in premix 1 mixture and carry out premix again in Mixers with Multi-direction Movement, after sieved by crushing and pelletizing machine, crushing and pelletizing machine adopts 1.0mm aperture screen cloth;
Total mixed: premix 2 mixture and lubricant to be put in Mixers with Multi-direction Movement, mix homogeneously.
Wherein said step 2) be preferably:
Premix 1: succinic acid YM-905 and binding agent are carried out premix in Mixers with Multi-direction Movement, mixing 2-10 minute, then add in crushing and pelletizing machine dispersion of sieving, crushing and pelletizing machine adopts 1.0mm aperture screen cloth;
Premix 2: add diluent in premix 1 mixture and carry out premix 2-10 minute again in Mixers with Multi-direction Movement, after sieved by crushing and pelletizing machine, crushing and pelletizing machine adopts 1.0mm aperture screen cloth;
Total mixed: premix 2 mixture and lubricant are put in Mixers with Multi-direction Movement, mixing 2-10 minute.
Adopt conventional method coating material coating after tabletting, coating weight gain is 2-4%.
Technique effect of the present invention is mainly reflected in:
1, by controlling active ingredient particle diameter, adopting repeatedly premix, total mixed etc. hybrid technique, solving succinic acid YM-905 is difficult to the content of guarantee homogeneity question because specification is little and have stronger aggregation;
2, wet granulation is compared, good with the succinic acid YM-905 tablet stability adopting direct compression process obtained;
3, technological operation is simple, is very applicable to suitability for industrialized production.
Specific embodiment
By specific embodiment given below, the present invention can be well understood to further, but they not limitation of the invention.
Following examples all adopt the measurement of M2000 Malvern laser particle size analyzer to obtain.
Embodiment 1
Prescription:
Technique:
1), succinic acid YM-905 through pulverize, particle diameter D0.9 is 82.617 μm;
2), mix:
Premix 1: the succinic acid YM-905 of recipe quantity and hydroxypropyl methylcellulose are carried out premix in Mixers with Multi-direction Movement, mixes 2 minutes, then adds in crushing and pelletizing machine dispersion of sieving, and crushing and pelletizing machine adopts 1.0mm aperture screen cloth;
Premix 2: add starch lactose in premix 1 mixture and carry out premix again 4 minutes in Mixers with Multi-direction Movement, after sieved by crushing and pelletizing machine, crushing and pelletizing machine adopts 1.0mm aperture screen cloth;
Total mixed: premix 2 mixture and magnesium stearate to be put in Mixers with Multi-direction Movement, mixes 8 minutes;
3), conventional method tabletting, coating weight gain 2%.
Embodiment 2
Prescription:
Technique:
1), succinic acid YM-905 through pulverize, particle diameter D0.9 is 82.617 μm;
2), mix:
Premix 1: the succinic acid YM-905 of recipe quantity and hydroxypropyl cellulose are carried out premix in Mixers with Multi-direction Movement, mixes 10 minutes, then adds in crushing and pelletizing machine dispersion of sieving, and crushing and pelletizing machine adopts 1.0mm aperture screen cloth;
Premix 2: add lactose, starch in premix 1 mixture and carry out premix again 5 minutes in Mixers with Multi-direction Movement, after sieved by crushing and pelletizing machine, crushing and pelletizing machine adopts 1.0mm aperture screen cloth;
Total mixed: premix 2 mixture and magnesium stearate to be put in Mixers with Multi-direction Movement, mixes 2 minutes;
3), conventional method tabletting, coating weight gain 3%.
Embodiment 3
Prescription:
Technique:
1), succinic acid YM-905 through pulverize, particle diameter D0.9 is 82.617 μm;
2), mix:
Premix 1: the succinic acid YM-905 of recipe quantity and polyvinylpyrrolidone are carried out premix in Mixers with Multi-direction Movement, mixes 6 minutes, then adds in crushing and pelletizing machine dispersion of sieving, and crushing and pelletizing machine adopts 1.0mm aperture screen cloth;
Premix 2: add lactose, starch in premix 1 mixture and carry out premix again 8 minutes in Mixers with Multi-direction Movement, after sieved by crushing and pelletizing machine, crushing and pelletizing machine adopts 1.0mm aperture screen cloth;
Total mixed: premix 2 mixture and calcium stearate to be put in Mixers with Multi-direction Movement, mixes 6 minutes;
3), conventional method tabletting, coating weight gain 4%.
Embodiment 4
Prescription:
Technique:
1), succinic acid YM-905 through pulverize, particle diameter D0.9 is 82.617 μm;
2), mix:
Premix 1: the succinic acid YM-905 of recipe quantity and hydroxypropyl methylcellulose are carried out premix in Mixers with Multi-direction Movement, mixes 7 minutes, then adds in crushing and pelletizing machine dispersion of sieving, and crushing and pelletizing machine adopts 1.0mm aperture screen cloth;
Premix 2: add dextrin, microcrystalline Cellulose in premix 1 mixture and carry out premix again 7 minutes in Mixers with Multi-direction Movement, after sieved by crushing and pelletizing machine, crushing and pelletizing machine adopts 1.0mm aperture screen cloth;
Total mixed: premix 2 mixture and Fu Ma sodium stearate magnesium to be put in Mixers with Multi-direction Movement, mixes 5 minutes;
3), conventional method tabletting, coating weight gain 3%.
Embodiment 5
Prescription:
Technique:
1), succinic acid YM-905 through pulverize, particle diameter D0.9 is 130.993 μm;
2), mix:
Premix 1: the succinic acid YM-905 of recipe quantity and hydroxypropyl methylcellulose are carried out premix in Mixers with Multi-direction Movement, mixes 8 minutes, then adds in crushing and pelletizing machine dispersion of sieving, and crushing and pelletizing machine adopts 1.0mm aperture screen cloth;
Premix 2: add microcrystalline Cellulose in premix 1 mixture and carry out premix again 10 minutes in Mixers with Multi-direction Movement, after sieved by crushing and pelletizing machine, crushing and pelletizing machine adopts 1.0mm aperture screen cloth;
Total mixed: premix 2 mixture and magnesium stearate to be put in Mixers with Multi-direction Movement, mixes 2 minutes;
3), conventional method tabletting, coating weight gain 3%.
Embodiment 6
Prescription:
Technique:
1), succinic acid YM-905 through pulverize, particle diameter D0.9 is 176.434 μm;
2), mix:
Premix 1: the succinic acid YM-905 of recipe quantity and hydroxypropyl methylcellulose are carried out premix in Mixers with Multi-direction Movement, mixes 5 minutes, then adds in crushing and pelletizing machine dispersion of sieving, and crushing and pelletizing machine adopts 1.0mm aperture screen cloth;
Premix 2: add mannitol, microcrystalline Cellulose in premix 1 mixture and carry out premix again 5 minutes in Mixers with Multi-direction Movement, after sieved by crushing and pelletizing machine, crushing and pelletizing machine adopts 1.0mm aperture screen cloth;
Total mixed: premix 2 mixture and magnesium stearate to be put in Mixers with Multi-direction Movement, mixes 6 minutes;
3), conventional method tabletting, coating weight gain 4%.
Embodiment 7
Prescription:
Technique:
1), succinic acid YM-905 through pulverize, particle diameter D0.9 is less than 200 μm;
2), mix:
Premix 1: the succinic acid YM-905 of recipe quantity and hydroxypropyl methylcellulose are carried out premix in Mixers with Multi-direction Movement, mixes 6 minutes, then adds in crushing and pelletizing machine dispersion of sieving, and crushing and pelletizing machine adopts 1.0mm aperture screen cloth;
Premix 2: add starch lactose in premix 1 mixture and carry out premix again 2 minutes in Mixers with Multi-direction Movement, after sieved by crushing and pelletizing machine, crushing and pelletizing machine adopts 1.0mm aperture screen cloth;
Total mixed: premix 2 mixture and magnesium stearate to be put in Mixers with Multi-direction Movement, mixes 10 minutes;
3), conventional method tabletting, coating weight gain 3%.
Embodiment 8
Prescription:
Technique:
1), succinic acid YM-905 through pulverize, particle diameter D0.9 is 82.617 μm;
2), mix:
Premix 1: the succinic acid YM-905 of recipe quantity and hydroxypropyl methylcellulose are carried out premix in Mixers with Multi-direction Movement, mixes 2 minutes, then adds in crushing and pelletizing machine dispersion of sieving, and crushing and pelletizing machine adopts 1.0mm aperture screen cloth;
Premix 2: add lactose, microcrystalline Cellulose in premix 1 mixture and carry out premix again 6 minutes in Mixers with Multi-direction Movement, after sieved by crushing and pelletizing machine, crushing and pelletizing machine adopts 1.0mm aperture screen cloth;
Total mixed: premix 2 mixture and magnesium stearate to be put in Mixers with Multi-direction Movement, mixes 6 minutes;
3), conventional method tabletting, coating weight gain 3%.
Embodiment 9
Prescription:
Technique:
1), succinic acid YM-905 through pulverize, particle diameter D0.9 is 82.617 μm;
2), mix:
Premix 1: the succinic acid YM-905 of recipe quantity and hydroxypropyl methylcellulose are carried out premix in Mixers with Multi-direction Movement, mixes 5 minutes, then adds in crushing and pelletizing machine dispersion of sieving, and crushing and pelletizing machine adopts 1.0mm aperture screen cloth;
Premix 2: add starch lactose in premix 1 mixture and carry out premix again 6 minutes in Mixers with Multi-direction Movement, after sieved by crushing and pelletizing machine, crushing and pelletizing machine adopts 1.0mm aperture screen cloth;
Total mixed: premix 2 mixture and magnesium stearate to be put in Mixers with Multi-direction Movement, mixes 6 minutes;
3), conventional method tabletting, coating weight gain 3%.
Embodiment 10
Check label friability according to Chinese Pharmacopoeia annex method, uniformity of dosage units, coated tablet checks dissolution, and nakedly under coated tablet being put 60 DEG C of hot conditionss puts 10 days, investigates stability; Temperature 25 ± 2 DEG C, humidity 60% ± 5% enter long term test 18 months, investigate stability.
Can see from result: prescription provided by the invention, technique compressibility is good, uniformity of dosage units conforms with the regulations, nakedly 60 DEG C of hot conditionss put 10 days total impuritieses and conform with the regulations;
Embodiment 7 diluent very little, causes dissolution on the low side;
Embodiment 8 binding agent very little, causes friability undesirable;
Embodiment 9 lubricant is excessive, causes sliver;
Within 18 months, investigate through long term test, although illustrate that commercially available product wet granulation has added PEG, long-time stability are still not as the product of direct compression production provided by the invention.Commercially available product adopts wet granulation, be add after the powder mix homogeneously by succinic acid YM-905 and adjuvant liquid adhesive prepare granule again through high temperature by the solvent removing in binding agent, carry out the process that granulate obtains suitable granule again, but test shows, succinic acid YM-905 is thermo-responsive, wet sensitive sense, cause related substance to increase, stability is bad.And PEG is high-hydrophilic material, hygroscopicity is strong, easily causes product moisture absorption, may affect stability in preparation process and storage.
Embodiment 11
Comparing of wet granulation and direct compression related substance and stability.
Prescription:
Technique:
Direct powder compression: the supplementary material taking recipe quantity, to put in the plastic bag of 26 × 47cm manual mixing 2 minutes, material moisture is 2.35%, and adopt 8mm circular die, direct powder compression, control strip is 150mg heavily about, and hardness is about 5Kg.
Wet granule compression tablet: take the supplementary material except magnesium stearate, to put in the plastic bag of 26 × 47cm manual mixing 2 minutes, adds appropriate purified water soft material, the manual granulation of sieving of 24 orders, 60 DEG C of dry 1h, pellet moisture is 2.10%, 30 order granulate, add magnesium stearate, mixing 30s, adopts 8mm circular die, tabletting, control strip is 150mg heavily about, and hardness is about 5Kg.
Tablet forming technique is on the impact of label related substance:
Related substance is carried out to label prepared by two kinds of techniques, puts 10d to two kinds of labels are naked under high temperature 60 DEG C of conditions simultaneously, carry out the investigation of stability:
Result shows that in the label of wet granule compression tablet, related substance is apparently higher than direct compression product, and nakedly under 60 DEG C of conditions puts 10d, and wet granule compression tablet product is always assorted to be increased more, illustrates that succinic acid YM-905 is more responsive to hot and humid condition.Because direct compression technique is better than wet granulation in related substance control, direct compression has technique simply simultaneously, lower-cost advantage, therefore selects direct compression process as the tablet forming technique of this product.
Embodiment 12
Being mixed directly property of supplementary material is tested.
Prescription:
Technique:
Take the supplementary material of 10000 tablet recipe amounts, crude drug particle diameter D0.9 is 364.887, puts mixing 2 minutes and sampling in 5 minutes in 20L Mixers with Multi-direction Movement, at 5 diverse location point sample analysis of mixed material, calculates RSD.
Result shows, supplementary material is unprocessed, and directly the content uniformity of mixing is poor, increases incorporation time and also fails to improve content uniformity.
Embodiment 13
Supplementary material pulverizes rear uniformity test.
Prescription:
Technique:
Take the crude drug of different-grain diameter respectively, add identical adjuvant, mixing, at 5 diverse location point sample analysis of mixed material, calculate RSD.
Mixing is divided into three steps to carry out:
Premix 1: the succinic acid YM-905 of the different-grain diameter of recipe quantity and binding agent are carried out premix in Mixers with Multi-direction Movement, mixes 2 minutes, then adds in crushing and pelletizing machine dispersion of sieving, and crushing and pelletizing machine adopts 1.0mm aperture screen cloth;
Premix 2: add diluent in premix 1 mixture and carry out premix again 4 minutes in Mixers with Multi-direction Movement, after sieved by crushing and pelletizing machine, crushing and pelletizing machine adopts 1.0mm aperture screen cloth;
Total mixed: premix 2 mixture and lubricant to be put in Mixers with Multi-direction Movement, mixes 6 minutes; Each 5 the some sample analysis of mixture, calculate RSD, evaluate mixing uniformity.
Result shows, succinic acid YM-905 is along with the reduction of particle diameter, and mixing homogeneity improves, particularly when in particle diameter 4, D0.9 is 82.617 μm, RSD is less than 2, and mixing uniformity is very good, and D0.9 is 25.814 μm in particle diameter 5, RSD does not improve further.When usual D0.9 is less than 10 μm, need micromill process, technical process is more complicated, and electrostatic force becomes large, has aggregate themselves to be inclined to, may be unfavorable for mix homogeneously, therefore controls crude drug particle diameter D0.9 and is greater than 10 μm.Test shows that the stripping of crude drug particle diameter on label is without impact, and therefore the D0.9 of succinic acid YM-905 is less than 200 μm, is preferably less than 150 μm, is most preferably less than 100 μm, is not less than 10 μm.
Claims (9)
1. the pharmaceutical composition containing succinic acid YM-905, by weight, comprising:
Succinic acid YM-905: 1 part;
Diluent: 20-30 part, preferably 25 parts;
Binding agent: 2-6 part, preferably 4 parts;
Lubricant: 0-0.4 part, preferably 0.2 part;
Wherein said compositions is tablet;
The employing direct compression process preparation of wherein said compositions.
2. pharmaceutical composition as claimed in claim 1, is characterized in that the D0.9 of described succinic acid YM-905 is 10um-200 μm, preferred 10um-150 μm, most preferably 10um-100 μm.
3. compositions as claimed in claim 1, is characterized in that described diluent is lactose, starch, starch lactose, dextrin, microcrystalline Cellulose, one or more in mannitol, preferred starch lactose.
4. compositions as claimed in claim 1, is characterized in that described binding agent is hydroxypropyl methylcellulose, hydroxypropyl cellulose, polyvinylpyrrolidone, preferred hydroxypropyl methylcellulose.
5. compositions as claimed in claim 1, is characterized in that described lubricant is stearic acid, magnesium stearate, calcium stearate, rich horse sodium stearate, preferred magnesium stearate.
6. prepare the method for pharmaceutical composition as claimed in claim 1, comprising:
1) succinic acid YM-905 particle diameter, is controlled;
2), succinic acid YM-905 and binding agent premix disperse afterwards and filler premix disperseing, more always to mix with lubricant;
3), conventional method tabletting.
7. preparation method as claimed in claim 6, is characterized in that described step 2) be:
Premix 1: succinic acid YM-905 and binding agent are carried out premix in Mixers with Multi-direction Movement, then adds in crushing and pelletizing machine dispersion of sieving, crushing and pelletizing machine adopts 1.0mm aperture screen cloth;
Premix 2: add diluent in premix 1 mixture and carry out premix again in Mixers with Multi-direction Movement, after sieved by crushing and pelletizing machine, crushing and pelletizing machine adopts 1.0mm aperture screen cloth;
Total mixed: premix 2 mixture and lubricant to be put in Mixers with Multi-direction Movement, mix homogeneously.
8. preparation method as claimed in claim 7, is characterized in that any incorporation time is once 2-10 minute.
9. preparation method as claimed in claim 6, adopt conventional method coating after it is characterized in that tabletting, coating weight gain is 2-4%.
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| CN201510851876.1A CN105395494A (en) | 2015-11-27 | 2015-11-27 | Medicine composition containing succinic acid solifenacin and preparation method of medicine composition |
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| CN201510851876.1A CN105395494A (en) | 2015-11-27 | 2015-11-27 | Medicine composition containing succinic acid solifenacin and preparation method of medicine composition |
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010097243A2 (en) * | 2009-02-27 | 2010-09-02 | Krka, D. D., Novo Mesto | Process for forming solid oral dosage forms of solifenacin and its pharmaceutically acceptable salts |
| EP2500013A1 (en) * | 2011-03-15 | 2012-09-19 | Alfred E. Tiefenbacher GmbH & Co. KG | Pharmaceutical composition comprising solifenacin |
| CN104523628A (en) * | 2014-12-24 | 2015-04-22 | 乐普药业股份有限公司 | Succinic acid solifenacin tablet capable of achieving direct powder compression and preparation method of succinic acid solifenacin tablet |
| CN104940152A (en) * | 2014-03-31 | 2015-09-30 | 成都国弘医药有限公司 | Pharmaceutical composition containing solifenacin succinate |
| CN105012961A (en) * | 2014-04-17 | 2015-11-04 | 江苏神龙药业有限公司 | Stable pharmaceutical composition and preparation method thereof |
-
2015
- 2015-11-27 CN CN201510851876.1A patent/CN105395494A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010097243A2 (en) * | 2009-02-27 | 2010-09-02 | Krka, D. D., Novo Mesto | Process for forming solid oral dosage forms of solifenacin and its pharmaceutically acceptable salts |
| EP2500013A1 (en) * | 2011-03-15 | 2012-09-19 | Alfred E. Tiefenbacher GmbH & Co. KG | Pharmaceutical composition comprising solifenacin |
| CN104940152A (en) * | 2014-03-31 | 2015-09-30 | 成都国弘医药有限公司 | Pharmaceutical composition containing solifenacin succinate |
| CN105012961A (en) * | 2014-04-17 | 2015-11-04 | 江苏神龙药业有限公司 | Stable pharmaceutical composition and preparation method thereof |
| CN104523628A (en) * | 2014-12-24 | 2015-04-22 | 乐普药业股份有限公司 | Succinic acid solifenacin tablet capable of achieving direct powder compression and preparation method of succinic acid solifenacin tablet |
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Application publication date: 20160316 |