CN111110679A - Pharmaceutical composition containing montelukast sodium - Google Patents
Pharmaceutical composition containing montelukast sodium Download PDFInfo
- Publication number
- CN111110679A CN111110679A CN201811281691.1A CN201811281691A CN111110679A CN 111110679 A CN111110679 A CN 111110679A CN 201811281691 A CN201811281691 A CN 201811281691A CN 111110679 A CN111110679 A CN 111110679A
- Authority
- CN
- China
- Prior art keywords
- montelukast sodium
- pharmaceutical composition
- sodium
- montelukast
- solution
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- LBFBRXGCXUHRJY-HKHDRNBDSA-M montelukast sodium Chemical compound [Na+].CC(C)(O)C1=CC=CC=C1CC[C@H](C=1C=C(\C=C\C=2N=C3C=C(Cl)C=CC3=CC=2)C=CC=1)SCC1(CC([O-])=O)CC1 LBFBRXGCXUHRJY-HKHDRNBDSA-M 0.000 title claims abstract description 76
- 229960001951 montelukast sodium Drugs 0.000 title claims abstract description 75
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 18
- 239000003814 drug Substances 0.000 claims abstract description 18
- 239000000243 solution Substances 0.000 claims description 40
- 239000008187 granular material Substances 0.000 claims description 27
- 238000005303 weighing Methods 0.000 claims description 22
- 238000002360 preparation method Methods 0.000 claims description 17
- 238000001035 drying Methods 0.000 claims description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 14
- 239000007788 liquid Substances 0.000 claims description 13
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 10
- 229930195725 Mannitol Natural products 0.000 claims description 10
- 239000000594 mannitol Substances 0.000 claims description 10
- 235000010355 mannitol Nutrition 0.000 claims description 10
- 239000000945 filler Substances 0.000 claims description 9
- 238000005469 granulation Methods 0.000 claims description 8
- 230000003179 granulation Effects 0.000 claims description 8
- 239000008213 purified water Substances 0.000 claims description 8
- STFSJTPVIIDAQX-LTRPLHCISA-M sodium;(e)-4-octadecoxy-4-oxobut-2-enoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCCOC(=O)\C=C\C([O-])=O STFSJTPVIIDAQX-LTRPLHCISA-M 0.000 claims description 8
- 239000007921 spray Substances 0.000 claims description 8
- 238000005507 spraying Methods 0.000 claims description 8
- 238000003756 stirring Methods 0.000 claims description 8
- 230000000007 visual effect Effects 0.000 claims description 8
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 7
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 7
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 7
- 239000000853 adhesive Substances 0.000 claims description 6
- 230000001070 adhesive effect Effects 0.000 claims description 6
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 4
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 4
- 239000000600 sorbitol Substances 0.000 claims description 4
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 3
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 3
- 229920002472 Starch Polymers 0.000 claims description 3
- 239000008101 lactose Substances 0.000 claims description 3
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 3
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 3
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 3
- 239000008107 starch Substances 0.000 claims description 3
- 235000019698 starch Nutrition 0.000 claims description 3
- 229920000881 Modified starch Polymers 0.000 claims description 2
- 239000007864 aqueous solution Substances 0.000 claims description 2
- MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 claims description 2
- 229960001855 mannitol Drugs 0.000 claims description 2
- 229940045902 sodium stearyl fumarate Drugs 0.000 claims description 2
- 239000011230 binding agent Substances 0.000 claims 1
- 238000009776 industrial production Methods 0.000 abstract description 3
- 229940079593 drug Drugs 0.000 abstract description 2
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- 239000000047 product Substances 0.000 description 17
- 238000012360 testing method Methods 0.000 description 12
- 238000000034 method Methods 0.000 description 11
- 229960005127 montelukast Drugs 0.000 description 11
- 239000013558 reference substance Substances 0.000 description 11
- UCHDWCPVSPXUMX-TZIWLTJVSA-N Montelukast Chemical compound CC(C)(O)C1=CC=CC=C1CC[C@H](C=1C=C(\C=C\C=2N=C3C=C(Cl)C=CC3=CC=2)C=CC=1)SCC1(CC(O)=O)CC1 UCHDWCPVSPXUMX-TZIWLTJVSA-N 0.000 description 10
- 239000012535 impurity Substances 0.000 description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 7
- 239000000126 substance Substances 0.000 description 6
- 238000007865 diluting Methods 0.000 description 5
- 239000012085 test solution Substances 0.000 description 5
- -1 7-chloro-2-quinolinyl Chemical group 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 4
- ZLOLVGQQYDQBMP-HKHDRNBDSA-N 2-[1-[[(1r)-1-[3-[(e)-2-(7-chloroquinolin-2-yl)ethenyl]phenyl]-3-[2-(2-hydroxypropan-2-yl)phenyl]propyl]sulfanylmethyl]cyclopropyl]acetic acid;n-cyclohexylcyclohexanamine Chemical class C1CCCCC1NC1CCCCC1.CC(C)(O)C1=CC=CC=C1CC[C@H](C=1C=C(\C=C\C=2N=C3C=C(Cl)C=CC3=CC=2)C=CC=1)SCC1(CC(O)=O)CC1 ZLOLVGQQYDQBMP-HKHDRNBDSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 238000004090 dissolution Methods 0.000 description 3
- 238000010828 elution Methods 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 238000009210 therapy by ultrasound Methods 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- PMZXXNPJQYDFJX-UHFFFAOYSA-N acetonitrile;2,2,2-trifluoroacetic acid Chemical compound CC#N.OC(=O)C(F)(F)F PMZXXNPJQYDFJX-UHFFFAOYSA-N 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 239000012738 dissolution medium Substances 0.000 description 2
- 238000007908 dry granulation Methods 0.000 description 2
- 238000010812 external standard method Methods 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 238000005286 illumination Methods 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- QFTNWCBEAVHLQA-XNTDXEJSSA-N 2-[1-[[1-[3-[(e)-2-(7-chloroquinolin-2-yl)ethenyl]phenyl]-3-[2-(2-hydroxypropan-2-yl)phenyl]propyl]sulfinylmethyl]cyclopropyl]acetic acid Chemical compound CC(C)(O)C1=CC=CC=C1CCC(S(=O)CC1(CC(O)=O)CC1)C1=CC=CC(\C=C\C=2N=C3C=C(Cl)C=CC3=CC=2)=C1 QFTNWCBEAVHLQA-XNTDXEJSSA-N 0.000 description 1
- LVZWSLJZHVFIQJ-UHFFFAOYSA-N Cyclopropane Chemical compound C1CC1 LVZWSLJZHVFIQJ-UHFFFAOYSA-N 0.000 description 1
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical group CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000007910 chewable tablet Substances 0.000 description 1
- 229940068682 chewable tablet Drugs 0.000 description 1
- 239000007919 dispersible tablet Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000012088 reference solution Substances 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 239000012488 sample solution Substances 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000012489 system suitability test solution Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
Classifications
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
Abstract
The invention belongs to the technical field of medicines, and particularly relates to a pharmaceutical composition containing montelukast sodium. The product of the invention has good stability and more excellent product quality; the product of the invention has simple and easy production operation and is suitable for industrial production.
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to a montelukast sodium-containing pharmaceutical composition and a preparation method of granules of the pharmaceutical composition.
Background
The montelukast sodium has the structure (+) -1- [ [ [ (1R) -1- [3- [ (1E) -2- (7-chloro-2-quinolinyl) -ethenyl ] phenyl ] -3- [2- (1-hydroxy-1-methylethyl) phenyl ] propyl ] thio ] methyl ] cyclopropaneacetic acid monosodium salt. Montelukast sodium is a white to off-white powder that is soluble in methanol, ethanol, and water, but poorly soluble in acetonitrile.
The montelukast sodium molecule contains a hydroxyl group, two methyl groups and a benzene ring on the terminal carbon atom, the steric hindrance is great, and related substances are gradually increased under the catalysis of temperature in the storage process of the montelukast sodium.
Chinese patent CN101732268A discloses a method for preparing montelukast sodium tablets, which adopts dry granulation and direct tabletting to avoid some influences caused by wet granulation, but the dry granulation is relatively complicated and has relatively high requirements on equipment, and the stability of the prepared tablets is not improved, and the tablets are easy to discolor and decompose when exposed to light.
Chinese patent CN1961867A discloses a montelukast sodium granule, Chinese patent CN1287792C discloses a montelukast sodium dispersible tablet, and Chinese patent CN101773481A discloses a chewable tablet containing montelukast sodium.
Disclosure of Invention
The invention aims to provide a novel pharmaceutical composition containing montelukast sodium, which has good stability.
Another object of the present invention is to provide a method for preparing a pharmaceutical composition containing montelukast sodium, which is suitable for industrial production.
Specifically, the present invention provides:
a pharmaceutical composition comprising montelukast sodium comprising: montelukast sodium, sodium stearyl fumarate, mannitol, a filler and an adhesive.
The pharmaceutical composition containing montelukast sodium is granules.
The pharmaceutical composition containing montelukast sodium comprises the following components in parts by weight:
the filler is selected from one or more of starch, lactose, sorbitol, microcrystalline cellulose and pregelatinized starch.
The adhesive is hydroxypropyl cellulose aqueous solution.
The pharmaceutical composition containing montelukast sodium is prepared into granules, and the preparation method comprises the following steps:
(1) weighing sodium octadecyl fumarate, mannitol and a filler in a formula amount, placing in a fluidized bed granulator, performing spray granulation by using an adhesive, and drying;
(2) preparation of montelukast sodium solution: weighing montelukast sodium in a prescription amount, adding the montelukast sodium into purified water, stirring until the montelukast sodium is completely dissolved by visual observation, and defoaming the liquid medicine completely for use;
(3) putting the dried granules obtained in the step (1) into a fluidized bed granulator, spraying and applying medicine to the granules obtained in the step (1) by using the montelukast sodium solution obtained in the step (2), and drying; and (5) obtaining the product.
Compared with the prior art, the invention has the following advantages and positive effects:
1. the product of the invention has good stability, and the content of related substances is less than or equal to 0.3 percent.
2. The product of the invention has simple and easy production operation and is suitable for industrial production.
Detailed Description
The present invention is further described in the following description of the specific embodiments, which is not intended to limit the invention, but various modifications and improvements can be made by those skilled in the art according to the basic idea of the invention, within the scope of the invention, as long as they do not depart from the basic idea of the invention.
[ related substances ] was carried out in the dark. Taking a proper amount of fine powder (about 50mg of montelukast) with the content determination item, putting the fine powder into a 50ml measuring flask, adding a proper amount of 90% methanol solution, carrying out ultrasonic treatment for 30 minutes to dissolve montelukast sodium, diluting the montelukast sodium to a scale with the 90% methanol solution, shaking up, centrifuging, and taking a supernatant as a test solution; an appropriate amount was precisely measured and diluted with 90% methanol solution to prepare a solution containing 1. mu.g of montelukast per 1ml, which was used as a control solution. The measurement is carried out according to high performance liquid chromatography (China pharmacopoeia 2015 edition of the general rules 0512 in four parts). Phenyl bonded silica gel as filler (ZORBAX SB-phenyl 4.6X 50mm, 1.8 μm or equivalent performance column); taking 0.15% trifluoroacetic acid solution as mobile phase A; taking 0.15% trifluoroacetic acid acetonitrile solution as mobile phase B; the flow rate was 1.0ml per minute; the column temperature was 40 ℃; the detection wavelength is 238 nm; the linear gradient elution was performed as follows. 10ml of the test solution was added with 17. mu.l of hydrogen peroxide, shaken, and irradiated under sunlight for 1 hour (or under 4000lx illumination for 10 minutes, or under ultraviolet light for 15 minutes) to prepare a system suitability test solution. Injecting 10 mu l of the mixture into a liquid chromatograph, and recording a chromatogram, wherein the retention time of the montelukast peak is about 15 minutes, and the separation degree of the impurity G peak and the montelukast peak is more than 2.5. Precisely measuring 10 μ l of each of the test solution and the control solution, respectively injecting into a liquid chromatograph, and recording chromatogram.
[ SOLUTION ] was carried out in the dark. Taking the product, determining dissolution and release according to determination method (0931 second method of general rules of four parts of Chinese pharmacopoeia 2015 edition), taking 900ml of 0.5% sodium dodecyl sulfate solution as dissolution medium, rotating speed 50 r/min, operating according to the method, taking appropriate amount of solution after 15 min, filtering, and taking subsequent filtrate as sample solution; and precisely weighing about 30mg of a montelukast dicyclohexylamine salt reference substance, putting the reference substance into a 100ml measuring flask, adding about 80ml of methanol, performing ultrasonic treatment for 10 minutes to dissolve the reference substance, cooling the reference substance, diluting the reference substance to a scale by using the methanol, shaking the reference substance uniformly, precisely weighing 2ml, putting the reference substance into the 100ml measuring flask, diluting the reference substance to the scale by using a dissolution medium, and shaking the reference substance uniformly to obtain a reference substance solution. According to the chromatographic conditions under the content uniformity, precisely measuring 25 μ l of each of the test solution and the reference solution, respectively injecting into a liquid chromatograph, and recording the chromatogram. The elution amount of each bag was calculated as peak area by external standard method.
[ CONTENT DETERMINATION ] is determined by high performance liquid chromatography (0512 in the four Ministry of pharmacopoeia 2015).
Chromatographic conditions and system applicability test using phenyl bonded silica gel as filler (ZORBAX SB-phenyl 4.6X 50mm, 1.8 μm or equivalent performance column); taking 0.15% trifluoroacetic acid solution as mobile phase A; taking 0.15% trifluoroacetic acid acetonitrile solution as mobile phase B; the flow rate was 1.0ml per minute; the column temperature is 40 ℃; the detection wavelength is 238 nm; the linear gradient elution was performed as follows. And (4) taking 10 mu l of system applicability test solution under related substance items, injecting the solution into a liquid chromatograph, and recording the chromatogram. The retention time of the montelukast peak is about 7 minutes and the degree of separation of the impurity G peak from the montelukast peak should be greater than 2.5.
[ assay ] working out in the dark. Taking 10 bags of the product, precisely weighing, and calculating the average filling amount. Grinding the content, precisely weighing a proper amount (about 60mg of montelukast), putting the weighed content into a 250ml measuring flask, adding 180ml of 75% methanol solution, shaking, performing ultrasonic treatment for 30 minutes, shaking constantly to dissolve montelukast sodium, cooling, diluting to a scale with the 75% methanol solution, shaking uniformly, filtering, precisely weighing 10 mu l of subsequent filtrate, injecting into a liquid chromatograph, and recording a chromatogram; taking about 33mg of montelukast dicyclohexylamine reference substance, precisely weighing, placing into a 100ml measuring flask, adding about 80ml of 75% methanol solution, shaking to dissolve, diluting with 75% methanol solution to scale, shaking uniformly, and measuring by the same method. The molecular weight of the montelukast is 586.18, the molecular weight of the montelukast dicyclohexylamine is 767.52, and the montelukast is obtained according to the external standard method by peak area calculation.
Impurity C:
the name of Chinese: [1- [ [ [1- [3- [ (E) -2- (7-chloroquinolin-2-yl) ethenyl ] phenyl ] -3- [2- (1-hydroxy-1-methylethyl) phenyl ] propyl ] sulfinyl ] methyl ] cyclopropyl ] acetic acid
Impurity G:
the name of Chinese: 1- [ [ [ (1R) -1-3- [ (1Z) -2- (7-chloro-2-quinolinyl) ethyl ] phenyl ] -3- [2- (1-hydroxy-1-methylethyl) phenyl ] propyl ] thio ] methyl ] cyclopropane ] acetic acid
Montelukast one:
the name of Chinese: (E) -1- {3- [2- (7-chloroquinolin-2-yl) vinyl ] phenyl } -3- [2- (2-hydroxypropyl-2-yl) phenyl ] -1-propanone
Test example 1: prescription screening test
Granules containing montelukast sodium were prepared according to the following formula (see table 1) by taking 4g of montelukast sodium (content: 99.9%, total impurities: 0.06%), respectively, and the dissolution rates and related substances were measured, and the results are shown in table 2:
TABLE 1 Montelukast sodium granule formulation (unit: g)
The preparation method comprises the following steps:
(1) weighing sodium octadecyl fumarate, mannitol and a filler in a formula amount, placing in a fluidized bed granulator, performing spray granulation by using an adhesive, and drying;
(2) preparation of montelukast sodium solution: weighing montelukast sodium in a prescription amount, adding the montelukast sodium into purified water, stirring until the montelukast sodium is completely dissolved by visual observation, and defoaming the liquid medicine completely for use;
(3) putting the dried granules obtained in the step (1) into a fluidized bed granulator, spraying and applying medicine to the granules obtained in the step (1) by using the montelukast sodium solution obtained in the step (2), and drying; and (5) obtaining the product.
TABLE 2 test results
The test result shows that: the montelukast sodium granules prepared by the prescription of the invention have no impurity C, no impurity G and no montelukast ketone detected, and the content of related substances is lower than 0.3 percent, which is better than other prescription examples.
Test example 2: test for influencing factor
The montelukast sodium granules obtained in example 3 and the product obtained according to the method described in example ZL02821212 (comparative example) were taken.
TABLE 3 examination and investigation results of sample influence factor test
And (4) conclusion: as can be seen from the above table, the product prepared by the process of the present invention has better stability at high temperature and high humidity than the comparative example; particularly, under the condition of illumination, the dissolution rate and the content of the product of the invention are both obviously superior to those of a comparative example.
Test example 3: accelerated test
The products of examples 3 and 5 and the product prepared according to the method of example ZL02821212 were subjected to accelerated testing and the results are shown in Table 3.
Table 4 montelukast sodium granule accelerated test data
Packaging: commercial package, consider conditions: the temperature is 40 ℃, and the humidity is 75%
And (4) conclusion: as can be seen from the above table, the product prepared by the process of the present invention has better stability under high humidity, high temperature and light than the comparative example.
Preparation example
Example 1
Prescription
Preparation method
(1) Weighing sodium octadecyl fumarate, mannitol and starch in a formula amount, placing in a fluidized bed granulator, performing spray granulation by using 4% (w/v) hydroxypropyl cellulose water solution, and drying;
(2) preparation of montelukast sodium solution: weighing montelukast sodium in a prescription amount, adding the montelukast sodium into purified water, stirring until the montelukast sodium is completely dissolved by visual observation, and defoaming the liquid medicine completely for use;
(3) putting the dried granules obtained in the step (1) into a fluidized bed granulator, spraying and applying medicine to the granules obtained in the step (1) by using the montelukast sodium solution obtained in the step (2), and drying; and (5) obtaining the product.
Example 2
Prescription
Preparation method
(1) Weighing sodium octadecyl fumarate, mannitol and lactose in a formula amount, placing in a fluidized bed granulator, performing spray granulation by using 4% (w/v) hydroxypropyl cellulose water solution, and drying;
(2) preparation of montelukast sodium solution: weighing montelukast sodium in a prescription amount, adding the montelukast sodium into purified water, stirring until the montelukast sodium is completely dissolved by visual observation, and defoaming the liquid medicine completely for use;
(3) putting the dried granules obtained in the step (1) into a fluidized bed granulator, spraying and applying medicine to the granules obtained in the step (1) by using the montelukast sodium solution obtained in the step (2), and drying; and (5) obtaining the product.
Example 3
Prescription
Preparation method
(1) Weighing sodium octadecyl fumarate, mannitol and sorbitol in the formula amount, placing in a fluidized bed granulator, performing spray granulation by using 4% (w/v) hydroxypropyl cellulose water solution, and drying;
(2) preparation of montelukast sodium solution: weighing montelukast sodium in a prescription amount, adding the montelukast sodium into purified water, stirring until the montelukast sodium is completely dissolved by visual observation, and defoaming the liquid medicine completely for use;
(3) putting the dried granules obtained in the step (1) into a fluidized bed granulator, spraying and applying medicine to the granules obtained in the step (1) by using the montelukast sodium solution obtained in the step (2), and drying; and (5) obtaining the product.
Example 4
Prescription
Preparation method
(1) Weighing sodium octadecyl fumarate, mannitol and sorbitol in the formula amount, placing in a fluidized bed granulator, performing spray granulation by using 4% (w/v) hydroxypropyl cellulose water solution, and drying;
(2) preparation of montelukast sodium solution: weighing montelukast sodium in a prescription amount, adding the montelukast sodium into purified water, stirring until the montelukast sodium is completely dissolved by visual observation, and defoaming the liquid medicine completely for use;
(3) putting the dried granules obtained in the step (1) into a fluidized bed granulator, spraying and applying medicine to the granules obtained in the step (1) by using the montelukast sodium solution obtained in the step (2), and drying; and (5) obtaining the product.
Example 5
Prescription
Preparation method
(1) Weighing sodium octadecyl fumarate, mannitol and microcrystalline cellulose in the formula amount, placing in a fluidized bed granulator, performing spray granulation by using 4% (w/v) hydroxypropyl cellulose water solution, and drying;
(2) preparation of montelukast sodium solution: weighing montelukast sodium in a prescription amount, adding the montelukast sodium into purified water, stirring until the montelukast sodium is completely dissolved by visual observation, and defoaming the liquid medicine completely for use;
(3) putting the dried granules obtained in the step (1) into a fluidized bed granulator, spraying and applying medicine to the granules obtained in the step (1) by using the montelukast sodium solution obtained in the step (2), and drying; and (5) obtaining the product.
Claims (6)
1. A pharmaceutical composition comprising montelukast sodium comprising: montelukast sodium, sodium stearyl fumarate, mannitol, a filler and an adhesive.
2. The pharmaceutical composition containing montelukast sodium according to claim 1, wherein the pharmaceutical composition containing montelukast sodium is in the form of granules.
3. The montelukast sodium-containing pharmaceutical composition according to claim 1, comprising the following components in parts by weight:
4. the montelukast sodium-containing pharmaceutical composition according to claim 1, characterized in that: the filler is selected from one or more of starch, lactose, sorbitol, microcrystalline cellulose and pregelatinized starch.
5. The pharmaceutical composition of claim 1, wherein the binding agent is an aqueous solution of hydroxypropylcellulose.
6. The pharmaceutical composition containing montelukast sodium according to claim 1, which is prepared in the form of granules, comprising the steps of:
(1) weighing sodium octadecyl fumarate, mannitol and a filler in a formula amount, placing in a fluidized bed granulator, performing spray granulation by using an adhesive, and drying;
(2) preparation of montelukast sodium solution: weighing montelukast sodium in a prescription amount, adding the montelukast sodium into purified water, stirring until the montelukast sodium is completely dissolved by visual observation, and defoaming the liquid medicine completely for use;
(3) putting the dried granules obtained in the step (1) into a fluidized bed granulator, spraying and applying medicine to the granules obtained in the step (1) by using the montelukast sodium solution obtained in the step (2), and drying; and (5) obtaining the product.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811281691.1A CN111110679A (en) | 2018-10-31 | 2018-10-31 | Pharmaceutical composition containing montelukast sodium |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811281691.1A CN111110679A (en) | 2018-10-31 | 2018-10-31 | Pharmaceutical composition containing montelukast sodium |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN111110679A true CN111110679A (en) | 2020-05-08 |
Family
ID=70484948
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811281691.1A Pending CN111110679A (en) | 2018-10-31 | 2018-10-31 | Pharmaceutical composition containing montelukast sodium |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111110679A (en) |
Citations (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1575163A (en) * | 2001-10-26 | 2005-02-02 | 麦克弗罗斯特(加拿大)公司 | Granule formulation |
| US20070184101A1 (en) * | 2006-02-09 | 2007-08-09 | Teva Pharmaceutical Industries Ltd. | Stable pharmaceutical formulations of montelukast sodium |
| US20100279993A1 (en) * | 2002-12-30 | 2010-11-04 | Mark Tawa | Pharmaceutical Propylene Glycol Solvate Compositions |
| CN104546851A (en) * | 2013-10-29 | 2015-04-29 | 北京韩美药品有限公司 | Particle composition as well as preparation method and preparation thereof |
| CN104644564A (en) * | 2013-11-25 | 2015-05-27 | 天津汉瑞药业有限公司 | Stable granular preparation containing montelukast and preparation method thereof |
| CN104840427A (en) * | 2014-02-13 | 2015-08-19 | 长春海悦药业有限公司 | Pharmaceutical composition containing montelukast sodium |
| JP2015221782A (en) * | 2014-04-28 | 2015-12-10 | 大原薬品工業株式会社 | Tablet containing montelukast sodium |
| CN105193743A (en) * | 2015-11-05 | 2015-12-30 | 石家庄市华新药业有限责任公司 | Montelukast sodium granular preparation and preparation method thereof |
| CN105456213A (en) * | 2015-12-31 | 2016-04-06 | 鲁南贝特制药有限公司 | Montelukast sodium tablet |
| CN106606497A (en) * | 2015-10-21 | 2017-05-03 | 浙江海力生制药有限公司 | Montelukast effervescence preparation and preparing method thereof |
| CN107998091A (en) * | 2018-01-21 | 2018-05-08 | 上海安必生制药技术有限公司 | A kind of montelukast sodium tablet and preparation method thereof |
| CN108057021A (en) * | 2017-12-25 | 2018-05-22 | 南京康舟医药科技有限公司 | A kind of Montelukast sodium granules and preparation method thereof |
-
2018
- 2018-10-31 CN CN201811281691.1A patent/CN111110679A/en active Pending
Patent Citations (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1575163A (en) * | 2001-10-26 | 2005-02-02 | 麦克弗罗斯特(加拿大)公司 | Granule formulation |
| MY148466A (en) * | 2001-10-26 | 2013-04-30 | Merck Frosst Canada Ltd | Granule formulation |
| US20100279993A1 (en) * | 2002-12-30 | 2010-11-04 | Mark Tawa | Pharmaceutical Propylene Glycol Solvate Compositions |
| US20070184101A1 (en) * | 2006-02-09 | 2007-08-09 | Teva Pharmaceutical Industries Ltd. | Stable pharmaceutical formulations of montelukast sodium |
| CN104546851A (en) * | 2013-10-29 | 2015-04-29 | 北京韩美药品有限公司 | Particle composition as well as preparation method and preparation thereof |
| WO2015062466A1 (en) * | 2013-10-29 | 2015-05-07 | 北京韩美药品有限公司 | Particle composition, preparation method and formulation therefor |
| CN104644564A (en) * | 2013-11-25 | 2015-05-27 | 天津汉瑞药业有限公司 | Stable granular preparation containing montelukast and preparation method thereof |
| CN104840427A (en) * | 2014-02-13 | 2015-08-19 | 长春海悦药业有限公司 | Pharmaceutical composition containing montelukast sodium |
| JP2015221782A (en) * | 2014-04-28 | 2015-12-10 | 大原薬品工業株式会社 | Tablet containing montelukast sodium |
| CN106606497A (en) * | 2015-10-21 | 2017-05-03 | 浙江海力生制药有限公司 | Montelukast effervescence preparation and preparing method thereof |
| CN105193743A (en) * | 2015-11-05 | 2015-12-30 | 石家庄市华新药业有限责任公司 | Montelukast sodium granular preparation and preparation method thereof |
| CN105456213A (en) * | 2015-12-31 | 2016-04-06 | 鲁南贝特制药有限公司 | Montelukast sodium tablet |
| CN108057021A (en) * | 2017-12-25 | 2018-05-22 | 南京康舟医药科技有限公司 | A kind of Montelukast sodium granules and preparation method thereof |
| CN107998091A (en) * | 2018-01-21 | 2018-05-08 | 上海安必生制药技术有限公司 | A kind of montelukast sodium tablet and preparation method thereof |
Non-Patent Citations (9)
| Title |
|---|
| GANDLA K，ET AL.: "Simultaneous RP-HPLC method for estimation of rupatadine fumarate and montelukast sodium in tablet dosage form", 《DER PHARMA CHEMICA》 * |
| GANDLA K，ET AL.: "Simultaneous RP-HPLC method for estimation of rupatadine fumarate and montelukast sodium in tablet dosage form", 《DER PHARMA CHEMICA》, vol. 04, no. 05, 31 December 2012 (2012-12-31), pages 1819 - 1825 * |
| 何朝星，等: "孟鲁司特钠口腔崩解片的制备及比格犬体内生物等效性研究", 中国药学杂志, vol. 53, no. 13, pages 189 - 195 * |
| 张红鸣，等: "片剂药物着色与配色", 染料与染色, vol. 12, no. 02, pages 159 - 162 * |
| 朱永光，等: "孟鲁司特钠颗粒处方工艺及其稳定性研究", 《中国医院用药评价与分析》 * |
| 朱永光，等: "孟鲁司特钠颗粒处方工艺及其稳定性研究", 《中国医院用药评价与分析》, vol. 1, no. 03, 31 December 2016 (2016-12-31), pages 3 - 7 * |
| 朱永光，等: "孟鲁司特钠颗粒处方工艺及其稳定性研究", 中国医院用药评价与分析, no. 1, pages 103 - 105 * |
| 王威,等: "儿童药物制剂现状及开发策略分析", 《中国医药工业杂志》 * |
| 王威,等: "儿童药物制剂现状及开发策略分析", 《中国医药工业杂志》, vol. 46, no. 04, 10 April 2015 (2015-04-10), pages 412 - 415 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103054815B (en) | L-084 oral solid formulation and preparation method thereof | |
| CN103193798B (en) | Cefixime compound and pharmaceutical composition thereof | |
| CN104840427B (en) | A kind of pharmaceutical composition containing Menglusitena | |
| CN103463130A (en) | Preparation method of compound paracetamol and amantadine hydrochloride capsule | |
| CN112121027A (en) | Medicinal composition of oseltamivir phosphate coated granules, application and preparation method | |
| WO2014101115A1 (en) | Montelukast sodium tablet composition and preparation method thereof | |
| CN109674754B (en) | Flupentixol and melitracen pharmaceutical composition and preparation thereof | |
| CN104473892B (en) | It is a kind of for faropenem composition of sodium of direct tablet compressing and preparation method thereof | |
| CN111110679A (en) | Pharmaceutical composition containing montelukast sodium | |
| CN105085549A (en) | Cefaclor compound, medicine composition of cefaclor compound and bromhexine hydrochloride, and preparation of cefaclor compound | |
| CN104997757A (en) | Rabeprazole sodium enteric-coated pellet capsule and preparation method thereof | |
| CN108030924A (en) | A kind of preparation method of high stability Aprepitant composition | |
| CN109908104B (en) | Amoxicillin capsule and preparation method thereof | |
| WO2017190715A1 (en) | An amorphous form of sofosbuvir, a method of its preparation and its stabilization | |
| CN107865826B (en) | Solid dispersion of E-configuration benzamide compound | |
| CN110787139A (en) | Montelukast sodium pharmaceutical composition | |
| CN108653214B (en) | Cefdinir granules and preparation method thereof | |
| CN104055741A (en) | Montelukast sodium tablet and preparation method thereof | |
| CN102499909B (en) | Itraconazole dispersible tablets and preparation method thereof | |
| CN110721171A (en) | Improved vibration source sheet and preparation method thereof | |
| CN107536831A (en) | A kind of composition and preparation method containing vildagliptin and melbine | |
| CN112535736A (en) | Entecavir composition and preparation method thereof | |
| CN105616368A (en) | Montelukast sodium tablet and preparation method thereof | |
| CN105748438B (en) | A method of microcapsules are prepared in conjunction with concave convex rod by acetylamino evericin | |
| CN113750070A (en) | Phencyclamate dimedone capsule |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| AD01 | Patent right deemed abandoned | ||
| AD01 | Patent right deemed abandoned |
Effective date of abandoning: 20240308 |