CN107753455A - A kind of tablet containing imidafenacin and preparation method thereof - Google Patents
A kind of tablet containing imidafenacin and preparation method thereof Download PDFInfo
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- CN107753455A CN107753455A CN201711052209.2A CN201711052209A CN107753455A CN 107753455 A CN107753455 A CN 107753455A CN 201711052209 A CN201711052209 A CN 201711052209A CN 107753455 A CN107753455 A CN 107753455A
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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
- A61K9/2095—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
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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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4174—Arylalkylimidazoles, e.g. oxymetazolin, naphazoline, miconazole
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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
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
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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
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
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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
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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
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/282—Organic compounds, e.g. fats
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Abstract
The invention discloses a kind of tablet containing imidafenacin and preparation method thereof, the tablet or its label include active component imidafenacin, filler, adhesive and lubricant, active component is first dissolved in alcohol solvent or ethanol water in the mixed solvent in its preparation process, then add adhesive and binder solution is made in water, then pelletizing press sheet is carried out with filler and lubricant.The invention can ensure that finished product Fast Stripping, in the application by raw material and adhesive step-wise dissolution in ethanol solution, then added in other mixed powder with solution state, uniformity of dosage units can be greatly improved；Using technique is dried under reduced pressure, with air insulated, its oxidative degradation impurity can be preferably reduced.Technical solution of the present invention has the advantages that dissolution is quick, oxidation impurities are small, uniformity of dosage units is good, and preparation technology is simple, is adapted to large-scale production.
Description
Technical field
The invention belongs to pharmaceutical technology field, and in particular to a kind of imidafenacin piece and preparation method thereof.
Background technology
Overactive bladder (OAB) is a kind of syndrome characterized by symptoms of urgency, be often accompanied by frequent micturition, urgent urination and
Enuresis nocturna, or with urge incontinence, the serious life quality for reducing patient.The population of the whole world about 5,000 ten thousand~100,000,000 suffers from wing
Guang over-activity disease is also more common than diabetes and peptic ulcer.Imidafenacin has diphenyl butanamide structure, is a kind of new
The efficient anticholinergic agent of type, its selectively acting block contraction of the choline to detrusor, maincenter and periphery in M3 and M1 acceptors
Adverse reaction is less.Imidafenacin piece (trade name) listed in June, 2007 in Japan, specification 0.1mg.
Because this product specification is minimum, need to pay close attention to its content uniformity in production process；Found in research, imidafenacin
Oxidative degradation impurity is also easy to produce under the high temperature conditions, therefore in sample is prepared, can (powder be straight by avoiding drying process
Pressure), reduce drying time (fluidized bed granulation or part pelletize) or air-isolation (vacuum drying) to reduce the oxidation impurities
Formation.
Chinese patent CN102579393A discloses a kind of raising imidafenacin uniformity of dosage units and the solid compositions of dissolution
Thing, supplementary material is subjected to micronization processes, improves drug-eluting and bioavilability；CN1028610 10A by imidafenacin with
The spray drying of the alpha-cyclodextrin aqueous solution obtains particle, then carries out subsequent treatment, to improve dissolution in vitro；Research process are sent out
It is existing, though imidafenacin solubility in water is extremely low, because specification is minimum, in the case of composition and proportioning are suitable, its
Dissolution belongs to Fast Stripping type, and dissolution in vitro is improved without increasing process.
Chinese patent CN103479594B provides a kind of imidafenacin diaphragm and preparation method thereof, using fluid bed system
Grain technique, tabletting are simultaneously coated, and can obtain the qualified sample of dissolution and uniformity of dosage units.
Chinese patent CN104415034A discloses that a kind of uniformity of dosage units is good, dissolution is rapid, the miaow of excellent in stability reaches
That new pharmaceutical compositions and preparation method thereof, imidafenacin is dissolved first by inertia nonvolatile solvent, reselection is porous
Property auxiliary material by drug absorption, obtain powder, finally mixed with disintegrant, excipient, tabletting.The complex operation, and to auxiliary
The selection of material especially nonvolatile solvent is limited to very much, and dosage must be very low, and operation limitation is a lot.
Chinese patent CN106580899A discloses a kind of method for preparing imidafenacin tablet, takes imidafenacin and hydrotropy
Agent dispersing and dissolving is in absolute ethyl alcohol, then is sprayed in auxiliary material, adds lubricant, direct tablet compressing after mixing, but the technique is not
It is very ripe and higher to the Property requirements of material.
The content of the invention
The purpose of the present invention is on the basis of existing technology, there is provided a kind of uniformity of dosage units is good, dissolution is quick and relevant
The stable imidafenacin tablet of material.
It is a further object of the present invention to provide a kind of preparation method of the tablet of above-mentioned imidafenacin.
Technical scheme is as follows：
A kind of imidafenacin tablet, it forms tablet or label by bulk drug and excipient, and wherein bulk drug is that miaow reaches that
Newly, excipient includes：Filler, adhesive and lubricant.
Further, the imidafenacin tablet or its label include active component imidafenacin, filler, adhesive and profit
Lubrication prescription, active component is first dissolved in alcohol solvent or ethanol water in the mixed solvent in its preparation process, then adds bonding
Binder solution is made in agent and water, then carries out pelletizing press sheet with filler and lubricant.
In a kind of preferred scheme, in the preparation process of imidafenacin tablet, active component is first added to ethanol water
In the mixed solvent, after stirring and dissolving, add adhesive and be uniformly dispersed and dissolve, be eventually adding water and stir that adhesive is made is molten
Liquid.Experiment is found, in the preparation process of imidafenacin tablet, the addition sequence of its each component influences the uniformity, molten of tablet
Go out speed and relevant content of material.The present invention uses in preparation process active component imidafenacin being first dissolved in ethanol water solvent
In, add adhesive and the binder solution containing active component is made in water, be eventually adding the granulation of other auxiliary materials.Experiment discovery,
Relative to the mode of other wet granulations, the dissolution rate of preparation can be not only improved using this mode of the present invention, may be used also
To improve the content of active principle in preparation, the uniformity of dosage units of each preparation is effectively lifted, can more reduce the total impurities in product
Content and maximum single miscellaneous content, moreover it is possible to improve the dissolution rate of active component.
In a kind of preferred scheme, in the preparation process of imidafenacin tablet, it is molten that filler is slowly added to adhesive
Softwood processed, then pelletizes in liquid, after obtained wet granular is dried, with mix lubricant, tabletting, coating.
During tablet granulation, drying mode can be to be dried under reduced pressure technique, forced air drying technique or fluidized drying work
Skill, but it is a discovery of the invention that can farthest reduce impurity content in product using technique is dried under reduced pressure, make in product
Total miscellaneous and maximum miscellaneous content of list reaches minimum, is more beneficial for the storage and use of tablet.Preferably, it is being dried under reduced pressure technique
In, for the vacuum used for -0.05~-0.5MPa, drying temperature is 45~65 DEG C, and drying time be 3~5h, moisture less than etc.
In 5%.
In a kind of preferred scheme, the ethanol water mixed solvent is 90~99% ethanol water mixed solvent, institute
State filler and be selected from microcrystalline cellulose and pregelatinized starch, the lubricant is selected from magnesium stearate；Described adhesive is selected from poly- dimension
Ketone.
In a kind of scheme, this imidafenacin tablet includes label and coating, and wherein label includes the group of following mass parts
Point：0.06~0.1 part of imidafenacin, 40~65 parts of pregelatinized starch, 45~65 parts of microcrystalline cellulose, 1~5 part of PVP, firmly
0.2~1 part of fatty acid magnesium.
In another scheme, each ingredient percent of label of tablet is as follows：Imidafenacin mass percent is
0.06%~0.1%, pregelatinized starch 40%~65%, microcrystalline cellulose 45%~65%, PVP K30 1%~5%, firmly
Fatty acid magnesium 0.2%~1%.
In a kind of preferred scheme, label includes the component of following mass parts：0.06~0.08 part of imidafenacin, pregelatinated
40~50 parts of starch, 45~55 parts of microcrystalline cellulose, 1~3 part of PVP, 0.2~0.5 part of magnesium stearate.
In another preferred scheme, each ingredient percent of label is as follows：Imidafenacin mass percent is 0.06
~0.08%, pregelatinized starch 40%~50%, microcrystalline cellulose 45%~55%, PVP K30 1%~3%, stearic acid
Magnesium 0.2~0.5%.
PVP is used in the present invention as adhesive, experiment is found, when the used in amounts of adhesive is kept in the reasonable scope,
This tablet can be just set to maintain higher dissolution rate and relatively low total impurities content and maximum single miscellaneous content, and too high or mistake
Low binder dosage is difficult to reach the effect.Preferable binder dosage is 1~5 part or 1%~5%, further preferred 1
~3 parts or 1%~3%.
In a kind of preferred scheme, label includes the component of following mass parts：1.0 parts of imidafenacin, pregelatinized starch 650
Part, 750 parts of microcrystalline cellulose, 42 parts of PVP, 4 parts of magnesium stearate, 420 parts of coating agent.
In a kind of preferred scheme, label includes the component of following mass parts：1.0 parts of imidafenacin, pregelatinized starch 700
Part, 700 parts of microcrystalline cellulose, 28 parts of PVP, 6 parts of magnesium stearate, 420 parts of coating agent.
In another preferred scheme, label includes the component of following mass parts：1.0 parts of imidafenacin, pregelatinized starch
650 parts, 750 parts of microcrystalline cellulose, 21 parts of PVP, 4 parts of magnesium stearate, 420 parts of coating agent.
The coating of Tablets can use existing stomach dissolution type thin film coating material.
The invention provides a kind of preparation method of imidafenacin piece, comprise the following steps：
(1) pre-process：Active component and auxiliary material are taken, it is standby after sieving；
(2) preparation of binder solution：Active component is dissolved in alcohol solvent or ethanol water in the mixed solvent, Ran Houjia
Enter adhesive and binder solution is made in water；
(3) pelletizing press sheet is coated：Filler is slowly added to softwood processed in binder solution, then pelletized, by what is obtained
After wet granular is dried, with mix lubricant, tabletting, coating.
In the preparation process of imidafenacin tablet, imidafenacin is taken, is added in appropriate 95% ethanol, after stirring and dissolving,
Add adhesive PVP K30, be eventually adding appropriate purified water become containing active compound 35~50% (preferably 40~
50%) v/v ethanol waters；After taking pregelatinized starch, microcrystalline cellulose well mixed, above-mentioned drug containing adhesive is slowly added to,
20 mesh are pelletized, and whole grain is in 20~80 (preferably 20~60) mesh.
It is as follows in method for preparing tablet thereof, preferable pelletization：Imidafenacin is taken, is added in appropriate 95% ethanol, stirring
After dissolving, adhesive PVP K30 is added, appropriate purified water is eventually adding and becomes the 48%v/v ethanol waters containing active compound
Solution；After taking pregelatinized starch, microcrystalline cellulose well mixed, above-mentioned drug containing adhesive is slowly added to, 20 mesh are pelletized, and 20~80
(preferably 20~60) mesh whole grain.
In tablet preparation, drying mode can be to be dried under reduced pressure technique, forced air drying technique or fluidized drying technique, but
It is a discovery of the invention that can farthest reduce impurity content in product using technique is dried under reduced pressure, make total miscellaneous in product
Reach minimum with maximum single miscellaneous content, be more beneficial for the storage and use of tablet.Preferably, in technique is dried under reduced pressure, adopt
Vacuum is -0.05~-0.5MPa, and drying temperature is 45~65 DEG C, and drying time is 3~5h, and moisture is less than or equal to
5%.
Above-mentioned method for preparing tablet thereof, number of unpacking in drying process should be less than being equal to three times.
It is as follows using technical scheme, advantage:
Scheme provided by the present invention, without carrying out micro mist or other processing to bulk drug, you can ensure that finished product dissolution is
Fast Stripping type, and be complete dissolution in 5min or so.The present invention in preparation method, by bulk drug and adhesive step-wise dissolution in
In ethanol solution, then other are added with solution state and mixed in powder, uniformity of dosage units can be greatly improved；Further use with air every
From being dried under reduced pressure technique；Pass through the mutual synergy of each feature so that final products can preferably reduce its active component oxygen
Change degradation impurity, ensure that relevant material grinds product better than original, improve the content of active principle in preparation, containing for each preparation is effectively ensured
Measure the uniformity；Auxiliary material kind provided by the invention grinds that product are completely the same, and technique is simple with original, workable.
Prepare embodiment
The present invention is further illustrated below by embodiment, but present disclosure is not limited to this completely.
Embodiment 1
Tablet formulation (10000 preparation unit amount)：
Preparation technology：
1st, pre-process
1.1 dispensing：Pregelatinized starch, microcrystalline cellulose are weighed by formula ratio, crosses 80 mesh sieves respectively, it is standby.
The preparation of 1.2 binder solutions：Formula ratio imidafenacin is taken to be added in the ethanol of 480g 95%, after stirring and dissolving,
It is slowly added to 42g PVP K30s to be uniformly dispersed, stirring and dissolving, adds purified water 600g and stir, it is standby.
2nd, pelletize, dry, whole grain
2.1 mix microcrystalline cellulose and pregelatinized starch, are slowly added to imidafenacin PVP K30 ethanol water system
Softwood, the granulation of 20 mesh.
Wet granular is placed in and is dried under reduced pressure in case by 2.2, and 50 DEG C of dryings to pellet moisture are not higher than 5%, 20 mesh whole grains.
3rd, it is total mixed
Particle is taken to be mixed with formula ratio magnesium stearate 10 minutes, intermediate detection.
4th, tabletting
According to intermediate testing result stator weight, from Ф 7.0mm scrobicula drift tablettings, hardness：30N~70N；The piece method of double differences
It is different：± 7.5%.
5th, it is coated
The preparation of 5.1 coating solutions：420g stomach dissolution type film coating powders are weighed, are slowly added into 2kg purified waters, wait to be coated
After powder is all added and is uniformly dispersed, continue stirring 45 minutes, produce；
5.2 put plain piece in high-efficiency coating machine, coating weight gain to 2%~5%.
Embodiment 2
Tablet formulation (10000 preparation unit amount)：
Preparation technology：
1st, pre-process
1.1 dispensing：Pregelatinized starch, microcrystalline cellulose are weighed by formula ratio, crosses 80 mesh sieves respectively, it is standby.
The preparation of 1.2 binder solutions：Formula ratio imidafenacin is taken to be added in the ethanol of 480g 95%, after stirring and dissolving,
It is slowly added to 28g PVP K30s to be uniformly dispersed, stirring and dissolving, adds purified water 600g and stir, it is standby.
2nd, pelletize, dry, whole grain
2.1 mix microcrystalline cellulose and pregelatinized starch, are slowly added to imidafenacin PVP K30 ethanol water system
Softwood, the granulation of 20 mesh.
Wet granular is placed in and is dried under reduced pressure in case by 2.2, and 50 DEG C of dryings to pellet moisture are not higher than 5%, 20 mesh whole grains.
3rd, it is total mixed
Particle is taken to be mixed with formula ratio magnesium stearate 10 minutes, intermediate detection.
4th, tabletting
According to intermediate testing result stator weight, from Ф 7.0mm scrobicula drift tablettings, hardness：30N~70N；The piece method of double differences
It is different：± 7.5%.
5th, it is coated
The preparation of 5.1 coating solutions：420g stomach dissolution type film coating powders are weighed, are slowly added into 2kg purified waters, wait to be coated
After powder is all added and is uniformly dispersed, continue stirring 45 minutes, produce；
5.2 put plain piece in high-efficiency coating machine, coating weight gain to 2%~5%.
Embodiment 3
Tablet formulation (10000 preparation unit amount)：
Preparation technology：
1st, pre-process
1.1 dispensing：Pregelatinized starch, microcrystalline cellulose are weighed by formula ratio, crosses 80 mesh sieves respectively, it is standby.
The preparation of 1.2 binder solutions：Formula ratio imidafenacin is taken to be added in the ethanol of 48g 95%, after stirring and dissolving,
It is slowly added to 21g PVP K30s to be uniformly dispersed, stirring and dissolving, adds purified water 60g and stir, it is standby.
2nd, pelletize, dry, whole grain
2.1 take portions microcrystalline cellulose, are slowly added to imidafenacin PVP K30 ethanol solution softwood, the granulation of 20 mesh.
Wet granular is placed in and is dried under reduced pressure in case by 2.2, and 50 DEG C of dryings to pellet moisture are not higher than 5%, 60 mesh whole grains.
3rd, it is total mixed
Particle is taken to be mixed 10 minutes with remaining microcrystalline cellulose, the pregelatinized starch of formula ratio and magnesium stearate, it is middle
Physical examination is surveyed.
4th, tabletting
According to intermediate testing result stator weight, from Ф 7.0mm scrobicula drift tablettings, hardness：30N~70N；The piece method of double differences
It is different：± 7.5%.
5th, it is coated
The preparation of 5.1 coating solutions：420g stomach dissolution type film coating powders are weighed, are slowly added into 2kg purified waters, wait to be coated
After powder is all added and is uniformly dispersed, continue stirring 45 minutes, produce；
5.2 put plain piece in high-efficiency coating machine, coating weight gain to 2%~5%.
Comparative example 1
Tablet formulation (10000 preparation unit amount)：
Preparation technology：
1st, pre-process
1.1 dispensing：Imidafenacin, pregelatinized starch, microcrystalline cellulose are weighed by formula ratio, crosses 80 mesh sieves respectively, it is standby.
The preparation of 1.2 binder solutions：The ethanol of 480g 95% is taken, 36g PVP K30s is slowly added to and is uniformly dispersed, is stirred
Dissolving, add purified water 600g and stir, it is standby.
2nd, pelletize, dry, whole grain
2.1 take the imidafenacin of formula ratio, are mixed respectively with pregelatinized starch, microcrystalline cellulose by the mixing method substep that progressively increases
Uniformly, binder solution softwood, the granulation of 20 mesh are slowly added to.
Wet granular is placed in and is dried under reduced pressure in case by 2.2, and 50 DEG C of dryings to pellet moisture are not higher than 5%, 20 mesh whole grains.
3rd, it is total mixed
Particle is taken to be mixed with the magnesium stearate of formula ratio 10 minutes, intermediate detection.
4th, tabletting
According to intermediate testing result stator weight, from Ф 7.0mm scrobicula drift tablettings, hardness：30N~70N；The piece method of double differences
It is different：± 7.5%.
5th, it is coated
The preparation of 5.1 coating solutions：420g stomach dissolution type film coating powders are weighed, are slowly added into 2kg purified waters, wait to be coated
After powder is all added and is uniformly dispersed, continue stirring 45 minutes, produce；
5.2 put plain piece in high-efficiency coating machine, coating weight gain to 2%~5%.
Comparative example 2
Tablet formulation (10000 preparation unit amount)：
Preparation technology：
Using forced air drying technique (oven drying), 50 DEG C of dryings to pellet moisture are not higher than 5%, and remaining step is with reference to real
Apply example 1.
Comparative example 3
Tablet formulation (10000 preparation unit amount)：
Preparation technology：
Using fluidized drying technique, EAT：60 DEG C, temperature of charge：40 DEG C, blower fan frequency：25Hz.Pellet moisture≤
5.0% stops drying.Remaining step is with reference to embodiment 1.
Comparative example 4 (CN103479594B comparative examples 1)
Tablet formulation (in terms of every 10000)：
Preparation technology：
1) take miaow to rattle away that new raw material, smash, cross 200 mesh sieves, it is standby；
2) take miaow to rattle away that new raw material, be slowly added into 60% ethanol water configured, stirring, dissolving, as viscous
Mixture, it is standby；
3) take microcrystalline cellulose, pregelatinized starch to be placed in Wet mixed granulating machine, stir 8 minutes, that will be rattled away dissolved with miaow
New adhesive is slowly homogeneously added into material, and with appropriate 60% ethanol water rinse adhesive tank, one
And add and softwood is prepared in material, cross the granulation of 24 mesh sieves；
4) wet granular is dried in 50 ± 5 DEG C of heated-air circulation ovens, and control moisture whole grain, calculates recovery 1.0~3.0%
Rate, outer addition magnesium stearate mix；
5) intermediate products physical examination：By main theory cubage theory piece weight, piece weight is calculated with theoretical piece weight ± 5% respectively
Control range, 7mm is selected to justify shallow stamping；
6) using Opadry as film coating agent, coating solution is made with 80% ethanol water and is coated, coating weight gain is extremely
3%~5%.
7) above-mentioned thin membrane coated tablet is taken, is entered with polyvinyl chloride solid medicinal stiff sheet, Key works Drug packing aluminium foil, Aluminum-plastic composite bag
Pack and produce.
Comparative example 5 (CN106361716A comparative examples 1)
Tablet formulation (with every 1000 gauge)：
Preparation technology：
The pregelatinized starch, microcrystalline cellulose (PH102) and PVP K30 of formula ratio is taken to mix at ambient temperature
Even, incorporation time 10min is standby；The imidafenacin of formula ratio is disperseed to be dissolved in appropriate absolute ethyl alcohol, it is standby；Will be above-mentioned
Absolute ethyl alcohol containing main ingredient is sprayed in above-mentioned auxiliary material, adds the magnesium stearate of formula ratio, is well mixed, incorporation time is
10min.Compress tablet coating produces.Determine intermediates content；Wherein tabletting hardness is 8kg, and mould is 7mm scrobiculas.
Embodiment 4, compliance test result (each check item can refer to the 4th progress of version Chinese Pharmacopoeia in 2015)
1st, the uniformity of dosage units (general rule 0941) of embodiment and comparative example is detected, concrete outcome is shown in Table 1
The embodiment sample uniformity of dosage units testing result of table 1
| Sample | Content (%) | Uniformity of dosage units (A+2.2S) |
| Embodiment 1 | 97.1 | 6.3 |
| Embodiment 2 | 98.5 | 5.7 |
| Embodiment 3 | 96.7 | 6.1 |
| Comparative example 1 | 99.6 | 11.0 |
| Comparative example 2 | 97.5 | 5.8 |
| Comparative example 3 | 96.9 | 6.0 |
| Comparative example 4 | / | 10.62(A+1.8S) |
| Comparative example 5 | / | 13.87(A+1.8S) |
2nd, relevant material, concrete outcome are shown in Table 2 to detection embodiment with the sample of comparative example
HPLC methods：
Chromatographic column：Octadecylsilane chemically bonded silica (5 μm, 4.6 μm of m*250mm, trade name：Inertsil ODS-3)
A liquid：The phosphoric acid solution of perfluorooctane sulfonate (takes 1.08g perfluorooctane sulfonates, adds 0.1% dilute phosphoric acid solution (1 → 1000)
Dissolve and be diluted to 1000ml, pH is adjusted to 2.8) with triethylamine
B liquid：Phase chromatography-use acetonitrile
Mobile phase：Change the mixed proportion of A liquid and B liquid to control gradient
Detector：UV
Determine wavelength：220nm
The relevant material testing result of the embodiment sample of table 2
3rd, the sample disintegration time limited (general rule 0921) of embodiment and comparative example is detected, concrete outcome is shown in Table 3
The embodiment sample disintegration time limited testing result of table 3
4th, the sample dissolution rate (general rule 0931) of embodiment and comparative example is detected, concrete outcome is shown in Table 4
The embodiment sample dissolution rate testing result of table 4
Claims (10)
- A kind of 1. tablet of imidafenacin, it is characterised in that the tablet or its label include active component imidafenacin, filler, Adhesive and lubricant, active component is first dissolved in alcohol solvent or ethanol water in the mixed solvent in its preparation process, so Adhesive is added afterwards and binder solution is made in water, then carries out pelletizing press sheet with filler and lubricant.
- 2. the tablet of imidafenacin according to claim 1, it is characterised in that in the preparation process of imidafenacin tablet, Active component is first added to ethanol water in the mixed solvent, after stirring and dissolving, adhesive is added and is uniformly dispersed and dissolves, finally plus Enter water and stir binder solution is made.
- 3. the tablet of imidafenacin according to claim 1, it is characterised in that in the preparation process of imidafenacin tablet, Filler is slowly added to softwood processed in binder solution, then pelletized, after obtained wet granular is dried, is mixed with lubricant Close, tabletting, coating.
- 4. the tablet of the imidafenacin according to claim 1,2 or 3, it is characterised in that the ethanol water mixed solvent is 90 ~99% ethanol water mixed solvent；Described adhesive is selected from PVP, and the filler is selected from microcrystalline cellulose and pregelatinated forms sediment Powder, the lubricant are selected from magnesium stearate.
- 5. the tablet of the imidafenacin according to claim 1,2 or 3, it is characterised in that the imidafenacin tablet includes label And coating, wherein label include the component of following mass parts：0.06 ~ 0.1 part of imidafenacin, 40 ~ 65 parts of pregelatinized starch are micro- 45 ~ 65 parts of crystalline cellulose, 1 ~ 5 part of PVP, 0.2 ~ 1 part of magnesium stearate.
- 6. the tablet of imidafenacin according to claim 5, it is characterised in that the label includes the group of following mass parts Point：0.06 ~ 0.08 part of imidafenacin, 40 ~ 50 parts of pregelatinized starch, 45 ~ 55 parts of microcrystalline cellulose, 1 ~ 3 part of PVP are stearic Sour 0.2 ~ 0.5 part of magnesium.
- 7. the preparation method of the tablet of the imidafenacin described in a kind of claim 1, it is characterised in that comprise the following steps：（1）Pretreatment：Active component and auxiliary material are taken, it is standby after sieving；（2）The preparation of binder solution：Active component is dissolved in alcohol solvent or ethanol water in the mixed solvent, then added viscous Binder solution is made in mixture and water；（3）Pelletizing press sheet is coated：Filler is slowly added to softwood processed in binder solution, then pelletized, will obtain wet After grain is dried, with mix lubricant, tabletting, coating.
- 8. the preparation method of the tablet of imidafenacin as claimed in claim 7, it is characterised in that the ethanol water mixed solvent For 90~99% ethanol water mixed solvent；Described adhesive is selected from PVP, and the filler is selected from microcrystalline cellulose and pre- glue Change starch, the lubricant is selected from magnesium stearate.
- 9. the preparation method of the tablet of imidafenacin as claimed in claim 7, it is characterised in that in step（3）In, drying side For formula to be dried under reduced pressure, vacuum is -0.05 ~ -0.5MPa, and drying temperature is 45 ~ 65 DEG C, and drying time is 3 ~ 5h, and moisture is less than Equal to 5%.
- 10. the preparation method of the tablet of imidafenacin as claimed in claim 7, it is characterised in that described adhesive solution be containing The ethanol water of active composition and adhesive, the volume ratio of ethanol is 35~50% in the ethanol water；Step（1）In Cross 80 mesh sieves；Step（3）In obtain 20 mesh after softwood and pelletize, 20 ~ 80 mesh whole grains after drying, coating uses stomach dissolution type film coating Material.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN110068623A (en) * | 2019-04-08 | 2019-07-30 | 南京海纳医药科技股份有限公司 | Detection method in relation to substance in a kind of imidafenacin |
| CN110772490A (en) * | 2019-10-31 | 2020-02-11 | 宁波高新区美诺华医药创新研究院有限公司 | Preparation method of apixaban tablets |
| CN113109461A (en) * | 2021-03-02 | 2021-07-13 | 南京海纳医药科技股份有限公司 | Method for detecting related substances in imidafenacin tablets |
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- 2017-10-30 CN CN201711052209.2A patent/CN107753455B/en active Active
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| 张进: "咪达那新片处方工艺及质量标准研究", 《中国优秀硕士学位论文全文数据库工程科技Ⅰ辑》 * |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN110068623A (en) * | 2019-04-08 | 2019-07-30 | 南京海纳医药科技股份有限公司 | Detection method in relation to substance in a kind of imidafenacin |
| CN110772490A (en) * | 2019-10-31 | 2020-02-11 | 宁波高新区美诺华医药创新研究院有限公司 | Preparation method of apixaban tablets |
| CN113109461A (en) * | 2021-03-02 | 2021-07-13 | 南京海纳医药科技股份有限公司 | Method for detecting related substances in imidafenacin tablets |
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