CN112137970A - Paroxetine hydrochloride orally disintegrating tablet and preparation process thereof - Google Patents
Paroxetine hydrochloride orally disintegrating tablet and preparation process thereof Download PDFInfo
- Publication number
- CN112137970A CN112137970A CN201910575281.6A CN201910575281A CN112137970A CN 112137970 A CN112137970 A CN 112137970A CN 201910575281 A CN201910575281 A CN 201910575281A CN 112137970 A CN112137970 A CN 112137970A
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- CN
- China
- Prior art keywords
- orally disintegrating
- disintegrating tablet
- paroxetine hydrochloride
- ewing
- coating
- 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.)
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Links
- AHOUBRCZNHFOSL-UHFFFAOYSA-N 3-(1,3-benzodioxol-5-yloxymethyl)-4-(4-fluorophenyl)piperidine Chemical compound C1=CC(F)=CC=C1C1C(COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-UHFFFAOYSA-N 0.000 title claims abstract description 48
- 229960005183 paroxetine hydrochloride Drugs 0.000 title claims abstract description 21
- 239000006191 orally-disintegrating tablet Substances 0.000 title claims abstract description 17
- 238000002360 preparation method Methods 0.000 title claims abstract description 14
- 238000000576 coating method Methods 0.000 claims abstract description 16
- 239000003814 drug Substances 0.000 claims abstract description 9
- 238000000034 method Methods 0.000 claims abstract description 9
- 239000002245 particle Substances 0.000 claims abstract description 7
- 238000005550 wet granulation Methods 0.000 claims abstract description 5
- 239000008187 granular material Substances 0.000 claims description 19
- 239000000463 material Substances 0.000 claims description 14
- 239000011248 coating agent Substances 0.000 claims description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 10
- 238000002156 mixing Methods 0.000 claims description 7
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
- 239000003826 tablet Substances 0.000 claims description 7
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 6
- 229920002785 Croscarmellose sodium Polymers 0.000 claims description 5
- 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 5
- 229930195725 Mannitol Natural products 0.000 claims description 5
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims description 5
- 239000000594 mannitol Substances 0.000 claims description 5
- 235000010355 mannitol Nutrition 0.000 claims description 5
- 239000000377 silicon dioxide Substances 0.000 claims description 5
- 235000012239 silicon dioxide Nutrition 0.000 claims description 5
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims description 4
- 238000003825 pressing Methods 0.000 claims description 4
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 claims description 3
- WBZFUFAFFUEMEI-UHFFFAOYSA-M Acesulfame k Chemical compound [K+].CC1=CC(=O)[N-]S(=O)(=O)O1 WBZFUFAFFUEMEI-UHFFFAOYSA-M 0.000 claims description 3
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 claims description 3
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 3
- 235000010358 acesulfame potassium Nutrition 0.000 claims description 3
- 229960004998 acesulfame potassium Drugs 0.000 claims description 3
- 239000000619 acesulfame-K Substances 0.000 claims description 3
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 3
- 229960001681 croscarmellose sodium Drugs 0.000 claims description 3
- 239000007884 disintegrant Substances 0.000 claims description 3
- 229940079593 drug Drugs 0.000 claims description 3
- 239000000796 flavoring agent Substances 0.000 claims description 3
- 239000000314 lubricant Substances 0.000 claims description 3
- 235000019359 magnesium stearate Nutrition 0.000 claims description 3
- 229940041616 menthol Drugs 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
- 229940124531 pharmaceutical excipient Drugs 0.000 claims description 3
- 229960000540 polacrilin potassium Drugs 0.000 claims description 3
- WVWZXTJUCNEUAE-UHFFFAOYSA-M potassium;1,2-bis(ethenyl)benzene;2-methylprop-2-enoate Chemical compound [K+].CC(=C)C([O-])=O.C=CC1=CC=CC=C1C=C WVWZXTJUCNEUAE-UHFFFAOYSA-M 0.000 claims description 3
- 230000004584 weight gain Effects 0.000 claims description 3
- 235000019786 weight gain Nutrition 0.000 claims description 3
- 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 2
- 108010011485 Aspartame Proteins 0.000 claims description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 2
- 235000016623 Fragaria vesca Nutrition 0.000 claims description 2
- 240000009088 Fragaria x ananassa Species 0.000 claims description 2
- 235000011363 Fragaria x ananassa Nutrition 0.000 claims description 2
- 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 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 2
- 229920002472 Starch Polymers 0.000 claims description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 2
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 2
- 239000000605 aspartame Substances 0.000 claims description 2
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 claims description 2
- 235000010357 aspartame Nutrition 0.000 claims description 2
- 229960003438 aspartame Drugs 0.000 claims description 2
- 229960000913 crospovidone Drugs 0.000 claims description 2
- 239000001767 crosslinked sodium carboxy methyl cellulose Substances 0.000 claims description 2
- 235000013355 food flavoring agent Nutrition 0.000 claims description 2
- 229940116298 l- malic acid Drugs 0.000 claims description 2
- 239000008101 lactose Substances 0.000 claims description 2
- 235000011090 malic acid Nutrition 0.000 claims description 2
- 229960001855 mannitol Drugs 0.000 claims description 2
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 claims description 2
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 claims description 2
- 229960001866 silicon dioxide Drugs 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- OKODKVMXHLUQSW-JITBQSAISA-M sodium;(e)-4-hydroxy-4-oxobut-2-enoate;octadecanoic acid Chemical compound [Na+].OC(=O)\C=C\C([O-])=O.CCCCCCCCCCCCCCCCCC(O)=O OKODKVMXHLUQSW-JITBQSAISA-M 0.000 claims description 2
- 239000008107 starch Substances 0.000 claims description 2
- 235000019698 starch Nutrition 0.000 claims description 2
- 235000002906 tartaric acid Nutrition 0.000 claims description 2
- 239000011975 tartaric acid Substances 0.000 claims description 2
- 235000019634 flavors Nutrition 0.000 claims 1
- 229940083542 sodium Drugs 0.000 claims 1
- 239000000454 talc Substances 0.000 claims 1
- 229910052623 talc Inorganic materials 0.000 claims 1
- 235000019640 taste Nutrition 0.000 abstract description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- AHOUBRCZNHFOSL-YOEHRIQHSA-N (+)-Casbol Chemical compound C1=CC(F)=CC=C1[C@H]1[C@H](COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-YOEHRIQHSA-N 0.000 description 6
- 238000004090 dissolution Methods 0.000 description 6
- 229960002296 paroxetine Drugs 0.000 description 6
- 239000000203 mixture Substances 0.000 description 5
- 238000004806 packaging method and process Methods 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- 229940123445 Tricyclic antidepressant Drugs 0.000 description 3
- 230000001430 anti-depressive effect Effects 0.000 description 3
- 239000000935 antidepressant agent Substances 0.000 description 3
- 229940005513 antidepressants Drugs 0.000 description 3
- 239000003029 tricyclic antidepressant agent Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 229920003163 Eudragit® NE 30 D Polymers 0.000 description 2
- YGCFIWIQZPHFLU-UHFFFAOYSA-N acesulfame Chemical compound CC1=CC(=O)NS(=O)(=O)O1 YGCFIWIQZPHFLU-UHFFFAOYSA-N 0.000 description 2
- 229960005164 acesulfame Drugs 0.000 description 2
- 235000019658 bitter taste Nutrition 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000007689 inspection Methods 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 239000008203 oral pharmaceutical composition Substances 0.000 description 2
- 238000000643 oven drying Methods 0.000 description 2
- 239000007779 soft material Substances 0.000 description 2
- 210000002700 urine Anatomy 0.000 description 2
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical class [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 1
- 229920003134 Eudragit® polymer Polymers 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 1
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 description 1
- RXUWDKBZZLIASQ-UHFFFAOYSA-N Puerarin Natural products OCC1OC(Oc2c(O)cc(O)c3C(=O)C(=COc23)c4ccc(O)cc4)C(O)C(O)C1O RXUWDKBZZLIASQ-UHFFFAOYSA-N 0.000 description 1
- 206010041250 Social phobia Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 229940069428 antacid Drugs 0.000 description 1
- 239000003159 antacid agent Substances 0.000 description 1
- 230000001458 anti-acid effect Effects 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 210000003608 fece Anatomy 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 208000024714 major depressive disease Diseases 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 208000019906 panic disease Diseases 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- HKEAFJYKMMKDOR-VPRICQMDSA-N puerarin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1C1=C(O)C=CC(C2=O)=C1OC=C2C1=CC=C(O)C=C1 HKEAFJYKMMKDOR-VPRICQMDSA-N 0.000 description 1
- 230000009103 reabsorption Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 238000007873 sieving Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4525—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with oxygen as a ring hetero atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
- A61K9/2081—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets with microcapsules or coated microparticles according to A61K9/50
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5015—Organic compounds, e.g. fats, sugars
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5026—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
- A61K9/5042—Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
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- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Neurosurgery (AREA)
- Medicinal Preparation (AREA)
- Psychiatry (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pain & Pain Management (AREA)
Abstract
The invention discloses a paroxetine hydrochloride orally disintegrating tablet and a preparation method thereof, which is characterized in that the orally disintegrating tablet is prepared by adopting a particle coating process after wet granulation. The process can obviously improve the taste of the medicine.
Description
Technical Field
The invention belongs to the field of pharmaceutical preparations, and particularly relates to a paroxetine hydrochloride orally disintegrating tablet and a preparation process thereof.
Background
Paroxetine hydrochloride (Paroxetine hydrochloride) is a Selective Serum Reabsorption Inhibitor (SSRI) type antidepressant, has similar antidepressant action intensity to tricyclic antidepressant (TCA), has obviously reduced side effects compared with TCA, and belongs to a third-generation antidepressant new drug. Puerarin Shike (China) investment Limited has marketed paroxetine immediate release tablets in 1996 in China for the treatment of major depressive disorder.
The paroxetine hydrochloride is easy to absorb by oral administration, is not influenced by antacid drugs or food, is orally taken for 30mg, has the peak concentration reaching time of 6.3h, the peak concentration of 17.6ug/ml, the T1/2 of 24h and the apparent volume of 3-28L/kg. The plasma protein binding rate was 95%. The plasma concentration reaches steady state within 7-14 days, and is rapidly distributed to various tissues and organs, and is metabolized in the liver, about 2 percent of the plasma is excreted from urine in the original shape, the rest is excreted from urine in the form of metabolite, and a small part is excreted from feces. The traditional Chinese medicine composition is clinically used for treating depression. Obsessive compulsive disorder, panic disorder, or social anxiety disorder may also be treated.
WO9520964A discloses an oral pharmaceutical composition containing a paroxetine resin complex to mask the bitter taste of paroxetine. CN104382870A discloses an oral pharmaceutical composition containing paroxetine polacrilin potassium hydrochloride to mask the bitter taste of paroxetine. But the preparation methods are all complex and are not easy to be industrially amplified. The paroxetine hydrochloride orally disintegrating tablet provided by the invention is simple in preparation process and beneficial to industrial production.
Disclosure of Invention
The invention aims to provide paroxetine orally disintegrating tablets which are good in taste, quick in disintegration and simple in preparation process. The invention relates to a granule coating process, which is characterized in that water-insoluble coating material Eudragit NE30D after wet granulation is used for granule coating, thereby achieving taste masking.
The invention provides that the excipient is selected from one or two of lactose, mannitol, microcrystalline cellulose, Ettqi RS100, Ettqi RL30D, Ettqi RD100, Ettqi NE30D, preferably mannitol, microcrystalline cellulose, Ettqi NE 30D.
The invention provides for the yutecky model number NE 30D.
The weight increment range of the Eudragit particle coating is specified to be 1.5-6.0%.
The invention provides that the disintegrant is selected from one or two of crospovidone, croscarmellose sodium, crosslinked acid methyl starch sodium and polacrilin potassium, and preferably the croscarmellose sodium.
The invention provides a flavoring agent which is one or two of aspartame, acesulfame, L-malic acid, strawberry essence, tartaric acid and menthol, preferably acesulfame and menthol.
The invention provides that the lubricant is selected from one or two of sodium stearate fumarate, magnesium stearate and talcum powder, and preferably magnesium stearate.
The invention also provides a preparation method of the paroxetine hydrochloride orally disintegrating tablet, and the specific embodiment is as follows.
(1) Mixing paroxetine hydrochloride, silicon dioxide, mannitol, acesulfame potassium and cross-linked sodium carboxymethyl cellulose, and preparing medicine particles by a wet process;
(2) coating the drug-containing granules obtained in the step (1) by adopting a granule coating process, and taking Eiteqi NE30D as a coating material;
(3) and (3) pressing the granule addition material obtained in the step (2) into tablets.
Detailed Description
Example 1:
note: the dosage of the raw materials and auxiliary materials in the table is 1000 dosage units
The preparation process comprises the following steps:
the paroxetine hydrochloride and the silicon dioxide are sieved by a 60-mesh sieve and mixed evenly, and then other auxiliary materials are mixed. Adding 30% ethanol to the mixture to prepare soft material, granulating with 24 mesh sieve, drying at 50 deg.C, controlling water content of granule below 3%, grading with 24 mesh sieve, mixing the obtained granule with the above materials, pressing into 1000 tablets, and packaging.
Example 2:
note: the dosage of the raw materials and auxiliary materials in the table is 1000 dosage units
The preparation process comprises the following steps:
the paroxetine hydrochloride and the silicon dioxide are sieved by a 60-mesh sieve and mixed evenly, and then other auxiliary materials are mixed. Adding 30% ethanol to the mixture, making into soft mass, granulating with 24 mesh sieve, oven drying at 50 deg.C, controlling granule moisture below 3%, grading with 24 mesh sieve, coating the obtained granule with Yttky NE30D, tabletting with a tabletting machine to obtain 1000 tablets, and packaging after inspection.
Example 3:
note: the dosage of the raw materials and auxiliary materials in the table is 1000 dosage units
The preparation process comprises the following steps:
the paroxetine hydrochloride and the silicon dioxide are sieved by a 60-mesh sieve and mixed evenly, and then other auxiliary materials are mixed. Adding 30% ethanol to the mixture, making into soft mass, granulating with 24 mesh sieve, oven drying at 50 deg.C, controlling granule moisture below 3%, grading with 24 mesh sieve, coating the obtained granule with Yttky NE30D, tabletting with a tabletting machine to obtain 1000 tablets, and packaging after inspection.
Example 4:
note: the dosage of the raw materials and auxiliary materials in the table is 1000 dosage units
The preparation process comprises the following steps:
sieving paroxetine hydrochloride and anhydrous calcium hydrogen phosphate with 60 mesh sieve, mixing, and mixing with other adjuvants. Adding 30% ethanol to the mixture to prepare soft material, granulating with 24 mesh sieve, drying at 50 deg.C, controlling water content of granule below 3%, grading with 24 mesh sieve, mixing the obtained granule with the above materials, pressing into 1000 tablets, and packaging.
The samples prepared in examples 1, 2, 3 and 4 were examined for the test items, and the comparison results are as follows:
from the comparison of the samples prepared in examples 1, 2, 3 and 4, it can be seen that several samples in 0.1M HCl medium showed fast dissolution (dissolution 15min > 85%) for examples 1, 2 and 3, all of which were fast dissolution. The dissolution rate of a sample prepared by mixing paroxetine hydrochloride alone with a pharmaceutical excipient through a wet method is reduced along with the increase of the weight gain of the Eudragit NE30D coating for 15min in an aqueous medium, and example 4 does not reach the rapid dissolution standard, but the taste is obviously improved. The weight gain of the medicine-containing particles is increased, and the dissolution of the medicine-containing particles in water medium for 15min is greatly reduced. The comparison shows that the paroxetine hydrochloride orally disintegrating tablet and the preparation method thereof can effectively mask the taste, have simple process and are easy for industrial large-scale production.
Claims (9)
1. The paroxetine hydrochloride orally disintegrating tablet is characterized in that paroxetine hydrochloride and pharmaceutic adjuvants are mixed by a 60-mesh sieve, granules are prepared by adopting a wet granulation process, and the orally disintegrating tablet capable of obviously improving the mouthfeel is prepared by adopting a Utex granule coating process.
2. The process of claim 1, wherein the paroxetine hydrochloride and the pharmaceutical excipient are mixed by passing through a 60 mesh sieve, and the pharmaceutical granules are prepared by a wet granulation process.
3. The method of claim 1, wherein the wet granulation process is used to prepare orally disintegrating tablets involving pharmaceutical excipients including excipients, disintegrants, flavors and lubricants.
4. The method of claim 1, wherein the weight gain of the ewing's special particle coating ranges from 1.5% to 6.0%.
5. The orally disintegrating tablet of claim 3, wherein said excipient is selected from one or two of lactose, mannitol, microcrystalline cellulose, Ewing RS100, Ewing RL30D, Ewing RD100, and Ewing NE 30D.
6. The orally disintegrating tablet of claim 3, wherein said disintegrant is selected from one or two of crospovidone, polacrilin potassium, croscarmellose sodium, and sodium carboxymethyl starch.
7. The orally disintegrating tablet of claim 5, wherein the flavoring agent is one or two selected from aspartame, acesulfame potassium, L-malic acid, strawberry essence, tartaric acid, and menthol.
8. The orally disintegrating tablet of claim 5, wherein said lubricant is one or two selected from the group consisting of sodium fumarate stearate, magnesium stearate, and talc.
9. A process for the preparation of an orally disintegrating tablet of paroxetine hydrochloride according to any one of claims 1 to 9 which comprises:
(1) mixing paroxetine hydrochloride, silicon dioxide, mannitol, acesulfame potassium and cross-linked sodium carboxymethyl cellulose, and preparing medicine particles by a wet process;
(2) coating the drug-containing granules obtained in the step (1) by adopting a granule coating process, and taking Eiteqi NE30D as a coating material;
(3) and (3) pressing the granule addition material obtained in the step (2) into tablets.
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| CN201910575281.6A CN112137970A (en) | 2019-06-28 | 2019-06-28 | Paroxetine hydrochloride orally disintegrating tablet and preparation process thereof |
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| CN201910575281.6A CN112137970A (en) | 2019-06-28 | 2019-06-28 | Paroxetine hydrochloride orally disintegrating tablet and preparation process thereof |
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030186938A1 (en) * | 2000-02-11 | 2003-10-02 | Al-Deeb Al-Ghazawi Ahmad Khalef | Water dispersible formulation of paroxetine |
| US20040242497A1 (en) * | 2001-08-09 | 2004-12-02 | Barges Causeret Nathalie Claude Marianne | Composition comprising paroxetine and a pharmaceutically acceptable glycyrrhizinate salt |
| CN1853631A (en) * | 2005-04-27 | 2006-11-01 | 上海秀新臣邦医药科技有限公司 | Fast disintegrant containing paroxetine |
| CN102631329A (en) * | 2012-04-12 | 2012-08-15 | 无锡万全医药技术有限公司 | Oral paroxetine disintegrating tablet and preparation process thereof |
| CN108938580A (en) * | 2017-05-26 | 2018-12-07 | 万全万特制药江苏有限公司 | Paroxetine hydrochloride oral disintegrating tablet |
-
2019
- 2019-06-28 CN CN201910575281.6A patent/CN112137970A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030186938A1 (en) * | 2000-02-11 | 2003-10-02 | Al-Deeb Al-Ghazawi Ahmad Khalef | Water dispersible formulation of paroxetine |
| US20040242497A1 (en) * | 2001-08-09 | 2004-12-02 | Barges Causeret Nathalie Claude Marianne | Composition comprising paroxetine and a pharmaceutically acceptable glycyrrhizinate salt |
| CN1853631A (en) * | 2005-04-27 | 2006-11-01 | 上海秀新臣邦医药科技有限公司 | Fast disintegrant containing paroxetine |
| CN102631329A (en) * | 2012-04-12 | 2012-08-15 | 无锡万全医药技术有限公司 | Oral paroxetine disintegrating tablet and preparation process thereof |
| CN108938580A (en) * | 2017-05-26 | 2018-12-07 | 万全万特制药江苏有限公司 | Paroxetine hydrochloride oral disintegrating tablet |
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