CN104644584A - Roflumilast tablet and preparation method thereof - Google Patents
Roflumilast tablet and preparation method thereof Download PDFInfo
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Abstract
The invention provides a roflumilast tablet. The roflumilast tablet comprises the following components in percentage by weight: 0.45-0.55% of roflumilast, 45-65% of lactose, 15-25% of starch, 4.5-15% of pre-gelled starch, 4.5-15% of povidone K30 and 0.25-2% of magnesium stearate. In addition, the invention further discloses a preparation method of the roflumilast tablet. According to the method, the roflumilast tablet is prepared by dissolving main medicines into a wetting agent and then carrying out wet granulation by spraying. By utilizing the method, the micro-powdering is not required in the main component, the process is simple, the loss of the main component during the micro-powdering process is reduced, the production cost is reduced, the content evenness of the prepared roflumilast tablet is good, and the quality is stable and reliable.
Description
Technical field
The invention belongs to medical art, more particularly, relate to and comprise a kind of chronic obstructive pulmonary disease (COPD) inhibitor Roflumilast tablet and preparation method thereof.
Background technology
Roflumilast is developed by German Anda (Altana) company at first, is at present uniquely can the phosphate IV inhibitor of oral medication chronic obstructive pulmonary disease (chronic obstructive pulmonary diseases is called for short COPD); Product under Metrizamide company of Switzerland (NycomedGmbH) at present.In March, 2011, the listing of U.S. FDA approval roflumilast, trade name Daliresp.Dosage form is tablet, and specification is 0.5mg, once a day, and each a slice.
Roflumilast chemistry 3-(cyclo propyl methoxy)-N-(3,5-dichloropyridine-4-base)-4-(difluoro-methoxy) Benzoylamide by name, English Roflumilast by name, molecular formula is C
17h
14cl
2f
2n
2o
3, molecular weight: 403.21, structural formula is as follows:
Show according to WHO statistics, the current whole world about has 600,000,000 people to suffer from chronic obstructive pulmonary disease, on average within every 10 seconds, just has a people dead because of COPD, occupies the 4th of the global cause of death.The mortality rate expecting the year two thousand twenty whole world chronic obstructive pulmonary disease more than 30%, maybe will will become the third-largest cause of the death in the whole world.Announce according to national health State Family Planning Commission, China is existing makes a definite diagnosis chronic close to 300,000,000 people, and the death that chronic disease causes has accounted for 85% of the total death of China, and the Disease Spectrum caused has accounted for 70% of total Disease Spectrum.In China, the investigation of the 14 years display consuming time that Zhong Nanshan academician presides over, in the Chinese population of more than 40 years old, the prevalence of COPD is up to 8.2%.The whole nation is every year because the number of COPD death reaches 1,000,000, and the number that disables reaches 500 ten thousand to 1,000 ten thousand.2012, chronic obstructive pulmonary disease is formally included in emphasis prevention and control chronic disease by Ministry of Public Health, and included in non-infective disease chronic disease prevention and control " 12 " planning first, clearly propose in China the prevalence of the chronic obstructive pulmonary disease of more than 40 years old crowd to be controlled below 8%.
Roflumilast is a kind of selectivity phosphodiesterase-4 (PDE4) inhibitor, and it, by suppressing the phosphodiesterase F-III making cAMP cracking, suppresses the cracking of cAMP, and increase intracellular cAMP concentration, increases Ca
++interior stream, produces positive inotropic action.Except positive inotropic action, phosphodiesterase inhibitor also has vasodilative effect by increasing cAMP content in vascular smooth muscle cell.4 type phosphodiesterase inhibitors can Immunosuppression and inflammatory cell as novel anti-inflammatory drug.It is relevant to chronic bronchitis and have the patients of severe COPD of frequent condition worse history that roflumilast is used for auxiliary bronchodilator maintaining treatment adult, to reduce the risk that COPD worsens, be current uniquely can phosphate-4 inhibitor of oral medication COPD.
Roflumilast is easily molten in dimethyl sulfoxide; Slightly molten in acetonitrile; Slightly soluble in isopropyl alcohol; Almost insoluble in water, almost insoluble at 0.1mol/L hydrochloric acid.Roflumilast to be classified 2 class medicines as BCS, there is low-solubility and high osmosis, therefore, roflumilast its be prepared into the oral solid formulations such as tablet and need to solve the dissolution problem of formulation products, and need other tablet quality index requests such as uniformity of dosage units be met.
The component and preparation method that specification is the Roflumilast tablet of 0.5mg is disclosed in the embodiment of the Chinese patent CN101171005A of Yuan Yan company application, wherein component is roflumilast (micronization), lactose monohydrate, corn starch, 30 POVIDONE K 30 BP/USP 90, magnesium stearate, adopts bed spray drying and granulating, tabletting, the method is high to equipment requirements.
Chinese patent CN102274222A discloses roflumilast medicinal composition of a kind of high bioavailability and preparation method thereof, said composition is made up of roflumilast, betacyclodextrin, lactose, microcrystalline Cellulose, magnesium stearate, adopt the method preparation of direct compression, the unexposed and former stripping Comparative result grinding product.Find after repeating the method, the Roflumilast tablet dissolution that the method prepares and the former medicine that grinds have larger gap.
Chinese patent CN102743353A discloses a kind of roflumilast tablet preparation and preparation method thereof, the method adopts and grinds the same drug component of product with former, i.e. roflumilast, starch, lactose, PVP, through wet granulation, tabletting, obtains grinding the more consistent dissolved corrosion of medicine with former.
Chinese patent CN102949370A discloses a kind of Roflumilast tablet and preparation method thereof and detection method, wherein component is roflumilast, lactose, pregelatinized Starch, PVP K30, magnesium stearate, adopting is dissolved in the mixed aqueous solution of acetone and ethanol by roflumilast and PVP K30, by bed spray drying and granulating, and tabletting, the method is high to equipment requirements, and easily has acetone and ethanol two kinds of organic solvent residuals.
Chinese patent CN103127011A discloses a kind of Roflumilast tablet and preparation method thereof, said composition has roflumilast (micronization), microcrystalline Cellulose, vertical compression lactose, pregelatinized Starch, cross-linking sodium carboxymethyl cellulose, carboxymethyl starch sodium, magnesium stearate form, adopt the method preparation of direct compression, direct and adjuvant mixed pressuring plate after the method carries out comminution by gas stream to raw material, but main constituent only accounts for 0.77%, there is the risk of mixing uniformity, and there is problems such as increasing equipment investment, loss of material is large, equipment cleaning is difficult in comminution by gas stream.
In said method, method disclosed in CN102274222A and CN103127011A is direct powder compression, and other is the method for wet granulation tabletting again.Those skilled in the art are known, though the tablet prepared by direct powder compression after micronization reduces granulating process, add raw material pulverizing operation, can increase loss of material cost, particularly small dimension preparation also easily exists the problem of mixing uniformity.Although CN102274222A and CN102743353A adopts wet granulation technology, raw material and adjuvant directly mix the risk that still there is mixing homogeneity, and CN102274222A adopts fluid bed preparation technology, also higher to equipment requirements; And although the method for CN102949370A have employed the technique added after main constituent is dissolved, but employ two kinds of organic solvents in process, although the Roflumilast tablet stripping prepared is consistent, easily there are acetone and ethanol two kinds of organic reagents to remain, and it adopts fluid bed preparation technology, high to equipment requirements.In order to further Simplified flowsheet, improve quality and the safety of product, take into account instrument and supplies requirement, and prepare the Roflumilast tablet of satisfactory quality, be necessary to study the method for wet granulation.
Summary of the invention
The invention provides a kind of Roflumilast tablet and preparation method, the method is for the deficiencies in the prior art, adopt wet granulation technology, principal agent is first dissolved with wetting agent after join in adjuvant, simplify processing step, reduce equipment cost, increase the dissolution of medicine, all be optimized the prescription of Roflumilast tablet, preparation technology, the Roflumilast tablet uniformity of dosage units prepared and dissolution are all qualified.
First object of the present invention is to provide the roflumilast tablet of a kind of dissolution and uniformity excellence.
Second object of the present invention is to provide the preparation method of above-mentioned roflumilast tablet.
Specifically, the invention provides a kind of Roflumilast tablet, the component of its percentage by weight is:
Wherein, used in the present invention " starch " and " pregelatinized Starch " is for there being two kinds of different auxiliary material of national standard.
In embodiments of the invention, the invention provides a kind of Roflumilast tablet, wherein, the part by weight of lactose, starch is 4: 1 ~ 2: 1, and the part by weight of starch, pregelatinized Starch is 3: 1 ~ 1: 1.
In embodiments of the invention, the invention provides a kind of Roflumilast tablet, wherein, sheet hardness is 40 ~ 110N.
In a kind of preferred embodiment of the present invention, the invention provides a kind of Roflumilast tablet, the component of its percentage by weight is:
In a kind of preferred embodiment of the present invention, the invention provides a kind of Roflumilast tablet, the component of its percentage by weight is:
In a kind of preferred embodiment of the present invention, the invention provides a kind of Roflumilast tablet, the component of its percentage by weight is:
In a kind of preferred embodiment of the present invention, the invention provides a kind of Roflumilast tablet, the component of its percentage by weight is:
In a kind of preferred embodiment of the present invention, the invention provides a kind of Roflumilast tablet, the component of its percentage by weight is:
In a kind of preferred embodiment of the present invention, the invention provides a kind of Roflumilast tablet, the component of its percentage by weight is:
In a kind of preferred embodiment of the present invention, the invention provides a kind of Roflumilast tablet, the component of its percentage by weight is:
On the other hand, the invention provides the preparation method of above-mentioned Roflumilast tablet, comprise the steps: to take the PVP K30 of recipe quantity, pregelatinized Starch, starch, lactose mixing of progressively progressively increasing, add in wet granulation pot and mix, take the roflumilast of recipe quantity again, the solution that concentration is 20 ~ 30mg/ml is mixed with 95 volume % ethanol, to be added in above-mentioned granulation pot and to stir granulation, dry, add the magnesium stearate mix homogeneously of recipe quantity, measure the content of mixture, calculate sheet weight, tabletting, to obtain final product.
In a kind of preferred embodiment of the present invention, preparation method provided by the invention, comprises the following steps:
(1) adjuvant mixing: take PVP K30, pregelatinized Starch, starch, lactose progressively to progressively increase mixing according to recipe quantity;
(2) preparation of wetting agent:
Get clean beaker, and agitator is installed, measure appropriate 95 volume % ethanol with graduated cylinder and put in beaker;
The roflumilast of precision weighing recipe quantity joins in above-mentioned 95 volume % ethanol while stirring, and solution is clarified, and makes 95 volume % alcoholic solution of roflumilast;
(3) mixed accessories is added in wet mixing pelletizer, machine and make mixing of materials 2 ~ 6min; Mixing speed setting 2 ~ 4r/s, cutting speed 20 ~ 40r/s;
(4) granulate: 95 volume % alcoholic solution of roflumilast are slowly at the uniform velocity joined in wet mixing pelletizer, add with after ethanol in proper amount rinse beaker again, mix and blend 120 seconds-240 seconds, shred 60 seconds-180 seconds in mixing process, before granulation terminates, with appropriate 95% ethanol purge beaker, until make suitable wet granular, the swing pelletizing machine of obtained wet granular is crossed 24 mesh sieve granulate;
(5) dry: the uniform particles stand after granulate is distributed in drip pan; Put into drying room; In 40 DEG C ~ 60 DEG C oven dry, terminal point control pellet moisture to 2% ~ 4%, dry end, rewinding;
(6) mix at granulate, end: the dry granule after drying is crossed 20 mesh sieve granulate.Add the magnesium stearate of recipe quantity, pour in stationary hopper mixer, mixing 4min ~ 10min.Granule content is 90.0 ~ 105.0% of labelled amount;
(7) tabletting: the heavy 100mg/ sheet of theoretical sheet,
punch die, diameter range: 6.5 ± 0.3mm, tableting pressure 6 ~ 16KN, tablet machine rotating speed 15 ~ 25rpm, hardness 40 ~ 110N.
Roflumilast raw material poorly water-soluble, as a rule, the particle diameter of raw material is less, is more conducive to the stripping improving medicine.Cover the equipment such as pulverizer, Universalpulverizer, jet mill by hammer crusher, vibromill, turbine grinder, ball mill, thunder raw material is pulverized, and former triturate adopts the method preparation of pulverizing Control granularity just.And the present inventor studies discovery, directly spray into the method for mixed accessories by dissolving raw material, raw material, without the need to comminution by gas stream, namely can reach qualified dissolution rate.
Because Roflumilast tablet specification of the present invention is 0.5mg, in prescription, proportion is less, and therefore, the kind of adjuvant and the selection of consumption become particularly important, otherwise will affect the dissolved corrosion of Roflumilast tablet, a large amount of research work has been done in the selection of inventor to adjuvant.
Because Roflumilast raw material is insoluble in water, suitable solvent need be selected to dissolve, we pass through the deliquescent investigation of roflumilast, final selection 95 volume % ethanol is as solvent, add direct wet granulation after adding material dissolution, well solve the problem of raw material granularity and the granule content uniformity.In addition, in tablet formulation, add hydrophilic adjuvant will contribute to the stripping of product, lactose is water soluble adjuvant, and starch and pregelatinized Starch then affect hardness and the disintegrate of preparation.The part by weight of adjustment lactose, starch is 4: 1 ~ 2: 1, and the part by weight of starch, pregelatinized Starch is 3: 1 ~ 1: 1, finished product stripping with former grind consistent.
The invention provides a kind of Roflumilast tablet and preparation method thereof, this invention has following advantage: 1, its uniformity of dosage units meets the requirements; 2, the method is without the need to controlling Roflumilast raw material granularity, shortens production technology; 3, the method adopts the preparation of conventional wet lay granulating tabletting process, and technique is simple, shortens the production cycle, reduces the cost of equipment and running; 4, sheet good appearance, technical process is smooth, and the product content uniformity is qualified, and dissolved corrosion is consistent with former triturate DALIRESP.
Detailed description of the invention
The detailed description of the invention of form by the following examples, is described in further detail foregoing of the present invention.But this should be interpreted as that the scope of the above-mentioned theme of the present invention is only limitted to following examples.
Stripping assay method: get this product, detects according to " Chinese Pharmacopoeia " two annex Ⅹ C dissolution detection method second methods, dissolution medium volume 900ml, rotating speed is 50 turns per minute, through 5,10,15,30,45,60 minutes time, get solution appropriate, filter, get subsequent filtrate as need testing solution; Separately get roflumilast reference substance appropriate, accurately weighed, put in 50ml measuring bottle, after adding the dissolving of a small amount of acetonitrile, make the solution about containing 2 μ g in every 1ml with dissolution medium dilution, product solution in contrast.Take octadecylsilane chemically bonded silica as filler, with the potassium dihydrogen phosphate-acetonitrile (50:50) of 0.02mol/L for mobile phase; , flow velocity is 1ml/min, determined wavelength 213nm.Precision measures need testing solution and reference substance solution 20ul respectively, injects chromatographic column, and record chromatogram, by external standard method with the stripping quantity of the every sheet of calculated by peak area.
embodiment 1
1, Roflumilast tablet is prepared (1000) by following Pharmaceutical ingredients:
2, preparation method
Take the PVP K30 of recipe quantity, pregelatinized Starch, starch, lactose progressively to progressively increase mixing, pour in wet granulation pot and mix, take the roflumilast of recipe quantity again, be mixed with 95% ethanol the solution that concentration is 25mg/ml, to be added in above-mentioned granulation pot and to stir granulation, dry, add the magnesium stearate mix homogeneously of recipe quantity, measure the content of mixture, calculate sheet weight, tabletting, to obtain final product.
3, the Roflumilast tablet of preparation has following characteristics:
3.1 Content uniformity tests: qualified.
3.2 disintegrations checked: disintegrate completely in 5min, disintegration phenomenon is identical with former triturate.
3.3 stripping curves detect: consistent with former triturate dissolved corrosion in each medium, concrete numerical value sees attached list.
embodiment 2
1, Roflumilast tablet is prepared (1000) by following Pharmaceutical ingredients:
2, preparation method
Take the PVP K30 of recipe quantity, pregelatinized Starch, starch, lactose progressively to progressively increase mixing, pour in wet granulation pot and mix, take the roflumilast of recipe quantity again, be mixed with 95% ethanol the solution that concentration is 22mg/ml, to be added in above-mentioned granulation pot and to stir granulation, dry, add the magnesium stearate mix homogeneously of recipe quantity, measure the content of mixture, calculate sheet weight, tabletting, to obtain final product.
3, the Roflumilast tablet of preparation has following characteristics:
3.1 Content uniformity tests: qualified.
3.2 disintegrations checked: disintegrate completely in 5min, disintegration phenomenon is identical with former triturate.
3.3 stripping curves detect: consistent with former triturate dissolved corrosion in each medium, concrete numerical value sees attached list.
embodiment 3
1, Roflumilast tablet is prepared (1000) by following Pharmaceutical ingredients:
2, preparation method
Take the PVP K30 of recipe quantity, pregelatinized Starch, starch, lactose progressively to progressively increase mixing, pour in wet granulation pot and mix, take the roflumilast of recipe quantity again, be mixed with 95% ethanol the solution that concentration is 26mg/ml, to be added in above-mentioned granulation pot and to stir granulation, dry, add the magnesium stearate mix homogeneously of recipe quantity, measure the content of mixture, calculate sheet weight, tabletting, to obtain final product.
3, the Roflumilast tablet of preparation has following characteristics:
3.1 Content uniformity tests: qualified.
3.2 disintegrations checked: disintegrate completely in 5min, disintegration phenomenon is identical with former triturate.
3.3 stripping curves detect: consistent with former triturate dissolved corrosion in each medium, concrete numerical value sees attached list.
embodiment 4
1, Roflumilast tablet is prepared (1000) by following Pharmaceutical ingredients:
2, preparation method
Take the PVP K30 of recipe quantity, pregelatinized Starch, starch, lactose progressively to progressively increase mixing, pour in wet granulation pot and mix, take the roflumilast of recipe quantity again, be mixed with 95% ethanol the solution that concentration is 24mg/ml, to be added in above-mentioned granulation pot and to stir granulation, dry, add the magnesium stearate mix homogeneously of recipe quantity, measure the content of mixture, calculate sheet weight, tabletting, to obtain final product.
3, the Roflumilast tablet of preparation has following characteristics:
3.1 Content uniformity tests: qualified.
3.2 disintegrations checked: disintegrate completely in 5min, disintegration phenomenon is identical with former triturate.
3.3 stripping curves detect: consistent with former triturate dissolved corrosion in each medium, concrete numerical value sees attached list.
embodiment 5
1, Roflumilast tablet is prepared (1000) by following Pharmaceutical ingredients:
2, preparation method
Take the PVP K30 of recipe quantity, pregelatinized Starch, starch, lactose progressively to progressively increase mixing, pour in wet granulation pot and mix, take the roflumilast of recipe quantity again, be mixed with 95% ethanol the solution that concentration is 28mg/ml, to be added in above-mentioned granulation pot and to stir granulation, dry, add the magnesium stearate mix homogeneously of recipe quantity, measure the content of mixture, calculate sheet weight, tabletting, to obtain final product.
3, the Roflumilast tablet of preparation has following characteristics:
3.1 Content uniformity tests: qualified.
3.2 disintegrations checked: disintegrate completely in 5min, disintegration phenomenon is identical with former triturate.
3.3 stripping curves detect: consistent with former triturate dissolved corrosion in each medium, concrete numerical value sees attached list.
embodiment 6
1, Roflumilast tablet is prepared (1000) by following Pharmaceutical ingredients:
2, preparation method
Take the PVP K30 of recipe quantity, pregelatinized Starch, starch, lactose progressively to progressively increase mixing, pour in wet granulation pot and mix, take the roflumilast of recipe quantity again, be mixed with 95% ethanol the solution that concentration is 25mg/ml, to be added in above-mentioned granulation pot and to stir granulation, dry, add the magnesium stearate mix homogeneously of recipe quantity, measure the content of mixture, calculate sheet weight, tabletting, to obtain final product.
3, the Roflumilast tablet of preparation has following characteristics:
3.1 Content uniformity tests: qualified.
3.2 disintegrations checked: disintegrate completely in 5min, disintegration phenomenon is identical with former triturate.
3.3 stripping curves detect: consistent with former triturate dissolved corrosion in each medium, concrete numerical value sees attached list.
comparative example 1 (micronization wet granulation process)
1, Roflumilast tablet is prepared (1000) by following Pharmaceutical ingredients:
2, preparation method
Roflumilast raw material jet mill is pulverized, for subsequent use; Take each supplementary material mix homogeneously of recipe quantity, add 5% appropriate 30 POVIDONE K 30 BP/USP 90 solution soft material, wet stock is crossed 20 mesh sieves to granulate, under wet granular being placed in 60 DEG C of conditions, carry out drying, after dry materials, magnesium stearate mix homogeneously is added according to the weight of dry granule, after the material detection level mixed, answer tabletting weight according to content conversion, carry out tabletting, regulate the hardness 2 ~ 3kg of tablet, content uniformity ± 5.0%.
3, the Roflumilast tablet of preparation has following characteristics:
3.1 Content uniformity tests: qualified, but compared with other formula, the RSD value of finished product content measurement result differs greatly.
3.2 disintegrations checked: disintegrate completely in 5min, disintegration phenomenon is identical with former triturate.
3.3 stripping curves detect: in each medium, stripping is partially slow, and the average dissolution of its 30min is all lower than 80%, and each f2 value is less than 50, can judge that the In Vitro Dissolution behavior of itself and former triturate does not have concordance.Concrete numerical value sees attached list.
comparative example 2 (direct compression process)
1, Roflumilast tablet is prepared (1000) by following Pharmaceutical ingredients:
2, preparation method
Roflumilast raw material jet mill is pulverized, for subsequent use; Take each supplementary material of 1000 tablet recipe amounts, the method of progressively increasing according to equivalent and cross-linking sodium carboxymethyl cellulose mix, mix homogeneously with microcrystalline Cellulose, vertical compression lactose, magnesium stearate successively again, after the material detection level mixed, tabletting weight is answered according to content conversion, carry out tabletting, regulate the hardness 2 ~ 3kg of tablet, content uniformity ± 5.0%.
3, the Roflumilast tablet of preparation has following characteristics:
3.1 Content uniformity tests: qualified, but compared with other formula, the RSD value of finished product content measurement result differs greatly.
3.2 disintegrations checked: disintegrate completely in 5min, disintegration phenomenon is identical with former triturate.
3.3 stripping curves detect: in each medium, stripping is partially slow, and the average dissolution of its 30min is only 80%, and stripping is partially slow.Concrete numerical value sees attached list.
comparative example 3 (fluidized bed process)
1, Roflumilast tablet is prepared (1000) by following Pharmaceutical ingredients:
2, preparation method
Roflumilast raw material and acetone, ethanol, purified water are stirred, adds PVP K30, make roflumilast solution; The lactose, the pregelatinized Starch that take 1000 tablet recipe amounts put into Multifunctional coating comminutor, mist projection granulating, dry, granulate; Add magnesium stearate mixing, tabletting, regulate the hardness 2 ~ 3kg of tablet, content uniformity ± 5.0%.
3, the Roflumilast tablet of preparation has following characteristics:
3.1 Content uniformity tests: defective, granule medicine-feeding rate is lower, and according to recipe quantity medicine-feeding, principal agent is with organic solvent loss about 10%, and formulation content is on the low side.
3.2 disintegrations checked: disintegrate completely in 5min, disintegration phenomenon is identical with former triturate.
3.3 stripping curves detect: in each medium, dissolution is on the low side, and the average dissolution of its 60min is only 85%, and concrete numerical value sees attached list.
Wherein, comparison example 1 is identical with the embodiment of the present application 6 formula, but directly mixes with adjuvant for after raw material micronization, then adopts wet granulation technology to obtain finished product; Comparison example 2, with reference to other patent formulations, adopts direct compression technique to obtain finished product; Comparison example 3 grinds patent formulation with reference to former, adopts fluidized bed granulation technique to obtain finished product.
Subordinate list 1: each embodiment sample and former triturate DALIRESP stripping curve comparing result in 0.1M hydrochloric acid medium
Subordinate list 2: each embodiment sample and former triturate DALIRESP stripping curve comparing result in aqueous
Subordinate list 3: each embodiment sample and former triturate DALIRESP stripping curve comparing result in pH4.0 medium
Subordinate list 4: each embodiment sample and former triturate DALIRESP stripping curve comparing result in pH6.8 medium
Claims (7)
1. a Roflumilast tablet, the component of its percentage by weight is:
2. Roflumilast tablet according to claim 1, wherein, the weight ratio of lactose, starch is 4: 1 ~ 2: 1, and the weight ratio of starch, pregelatinized Starch is 3: 1 ~ 1: 1.
3. Roflumilast tablet according to claim 1, wherein, sheet hardness 40 ~ 110N.
4. Roflumilast tablet according to claim 1, the component of its percentage by weight is:
5. Roflumilast tablet according to claim 1, the component of its percentage by weight is:
Or:
Or
Or
Or
Or
6. the preparation method of the Roflumilast tablet according to any one of claim 1-5, comprise the steps: to take the PVP K30 of recipe quantity, pregelatinized Starch, starch, lactose mixing of progressively progressively increasing, pour in wet granulation pot and mix, take the roflumilast of recipe quantity again, the solution that concentration is 20 ~ 30mg/ml is mixed with 95 volume % ethanol, to be added in above-mentioned granulation pot and to stir granulation, dry, add the magnesium stearate mix homogeneously of recipe quantity, measure the content of mixture, calculate sheet weight, tabletting, to obtain final product.
7. the preparation method of Roflumilast tablet according to claim 6, comprises the steps:
(1) adjuvant mixing: take PVP K30, pregelatinized Starch, starch, lactose progressively to progressively increase mixing according to recipe quantity;
(2) preparation of wetting agent:
Get clean beaker, and agitator is installed, measure appropriate 95 volume % ethanol with graduated cylinder and put in beaker;
The roflumilast of precision weighing recipe quantity joins in above-mentioned 95 volume % ethanol while stirring, and solution is clarified, and makes 95 volume % alcoholic solution of roflumilast;
(3) mixed accessories is added in wet mixing pelletizer, machine and make mixing of materials 2 ~ 6min; Mixing speed setting 2 ~ 4r/s, cutting speed 20 ~ 40r/s;
(4) granulate: 95 volume % alcoholic solution of roflumilast are slowly at the uniform velocity joined in wet mixing pelletizer, add with after ethanol in proper amount rinse beaker again, mix and blend 120 seconds-240 seconds, shred 60 seconds-180 seconds in mixing process, before granulation terminates, with appropriate 95% ethanol purge beaker, until make suitable wet granular, the swing pelletizing machine of obtained wet granular is crossed 24 mesh sieve granulate;
(5) dry: the uniform particles stand after granulate is distributed in drip pan; Put into drying room; In 40 DEG C ~ 60 DEG C oven dry, terminal point control pellet moisture to 2% ~ 4%, dry end, rewinding;
(6) mix at granulate, end: the dry granule after drying is crossed 20 mesh sieve granulate, adds the magnesium stearate of recipe quantity, pour in stationary hopper mixer, mixing 4min ~ 10min, granule content is 90.0 ~ 105.0% of labelled amount;
(7) tabletting: the heavy 100mg/ sheet of theoretical sheet,
punch die, diameter range: 6.5 ± 0.3mm, tableting pressure 6 ~ 16KN, tablet machine rotating speed 15 ~ 25rpm, hardness 40 ~ 110N.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN109512796A (en) * | 2018-12-26 | 2019-03-26 | 甘肃普安制药股份有限公司 | Method for filling paracetamol capsules |
| CN111643470A (en) * | 2020-04-30 | 2020-09-11 | 山东希尔康泰药业有限公司 | Preparation process of roflumilast film-coated tablets |
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| CN109512796A (en) * | 2018-12-26 | 2019-03-26 | 甘肃普安制药股份有限公司 | Method for filling paracetamol capsules |
| CN111643470A (en) * | 2020-04-30 | 2020-09-11 | 山东希尔康泰药业有限公司 | Preparation process of roflumilast film-coated tablets |
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Application publication date: 20150527 |