CN115531338A - Febuxostat tablet and preparation method thereof - Google Patents
Febuxostat tablet and preparation method thereof Download PDFInfo
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- CN115531338A CN115531338A CN202211337809.4A CN202211337809A CN115531338A CN 115531338 A CN115531338 A CN 115531338A CN 202211337809 A CN202211337809 A CN 202211337809A CN 115531338 A CN115531338 A CN 115531338A
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- febuxostat
- parts
- tablet according
- dodecyl sulfate
- sodium dodecyl
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- BQSJTQLCZDPROO-UHFFFAOYSA-N febuxostat Chemical compound C1=C(C#N)C(OCC(C)C)=CC=C1C1=NC(C)=C(C(O)=O)S1 BQSJTQLCZDPROO-UHFFFAOYSA-N 0.000 title claims abstract description 54
- 229960005101 febuxostat Drugs 0.000 title claims abstract description 52
- 238000002360 preparation method Methods 0.000 title abstract description 9
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims abstract description 36
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 claims abstract description 24
- 239000011248 coating agent Substances 0.000 claims abstract description 21
- 229960001275 dimeticone Drugs 0.000 claims abstract description 17
- CXQXSVUQTKDNFP-UHFFFAOYSA-N octamethyltrisiloxane Chemical group C[Si](C)(C)O[Si](C)(C)O[Si](C)(C)C CXQXSVUQTKDNFP-UHFFFAOYSA-N 0.000 claims abstract description 17
- 238000002156 mixing Methods 0.000 claims abstract description 15
- 239000000945 filler Substances 0.000 claims abstract description 9
- 239000000314 lubricant Substances 0.000 claims abstract description 9
- 239000004094 surface-active agent Substances 0.000 claims abstract description 9
- 239000007884 disintegrant Substances 0.000 claims abstract description 8
- 239000000463 material Substances 0.000 claims abstract description 7
- 239000004480 active ingredient Substances 0.000 claims abstract description 6
- 239000000853 adhesive Substances 0.000 claims abstract description 6
- 230000001070 adhesive effect Effects 0.000 claims abstract description 6
- 239000002518 antifoaming agent Substances 0.000 claims abstract description 4
- 239000003814 drug Substances 0.000 claims description 19
- 238000000576 coating method Methods 0.000 claims description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 11
- 239000008187 granular material Substances 0.000 claims description 7
- 239000011259 mixed solution Substances 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 239000007864 aqueous solution Substances 0.000 claims description 4
- 238000001035 drying Methods 0.000 claims description 4
- 230000002496 gastric effect Effects 0.000 claims description 4
- 238000005469 granulation Methods 0.000 claims description 4
- 230000003179 granulation Effects 0.000 claims description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- 239000000843 powder Substances 0.000 claims description 4
- 239000008213 purified water Substances 0.000 claims description 4
- 238000003756 stirring Methods 0.000 claims description 4
- 238000000034 method Methods 0.000 claims description 3
- UPUIQOIQVMNQAP-UHFFFAOYSA-M sodium;tetradecyl sulfate Chemical compound [Na+].CCCCCCCCCCCCCCOS([O-])(=O)=O UPUIQOIQVMNQAP-UHFFFAOYSA-M 0.000 claims description 3
- 229910002012 Aerosil® Inorganic materials 0.000 claims description 2
- 229920002261 Corn starch Polymers 0.000 claims description 2
- 229920002785 Croscarmellose sodium Polymers 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
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 2
- 229920002472 Starch Polymers 0.000 claims description 2
- 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 2
- 239000011230 binding agent Substances 0.000 claims description 2
- 239000008120 corn starch Substances 0.000 claims description 2
- 229960001681 croscarmellose sodium Drugs 0.000 claims description 2
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims description 2
- 239000008101 lactose Substances 0.000 claims description 2
- 235000019359 magnesium stearate Nutrition 0.000 claims description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 2
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 2
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 claims description 2
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- 229960000776 sodium tetradecyl sulfate Drugs 0.000 claims description 2
- 239000008107 starch Substances 0.000 claims description 2
- 235000019698 starch Nutrition 0.000 claims description 2
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims 5
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 238000004090 dissolution Methods 0.000 abstract description 16
- 230000003381 solubilizing effect Effects 0.000 abstract description 4
- 230000009471 action Effects 0.000 abstract description 2
- 230000009286 beneficial effect Effects 0.000 abstract description 2
- 239000013530 defoamer Substances 0.000 abstract description 2
- 230000000694 effects Effects 0.000 description 18
- 229940079593 drug Drugs 0.000 description 16
- 230000000052 comparative effect Effects 0.000 description 15
- LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 description 8
- TVWHNULVHGKJHS-UHFFFAOYSA-N Uric acid Natural products N1C(=O)NC(=O)C2NC(=O)NC21 TVWHNULVHGKJHS-UHFFFAOYSA-N 0.000 description 8
- 229940116269 uric acid Drugs 0.000 description 8
- 201000005569 Gout Diseases 0.000 description 7
- 108010093894 Xanthine oxidase Proteins 0.000 description 7
- 229960003459 allopurinol Drugs 0.000 description 7
- OFCNXPDARWKPPY-UHFFFAOYSA-N allopurinol Chemical compound OC1=NC=NC2=C1C=NN2 OFCNXPDARWKPPY-UHFFFAOYSA-N 0.000 description 7
- 235000013870 dimethyl polysiloxane Nutrition 0.000 description 7
- 239000004205 dimethyl polysiloxane Substances 0.000 description 7
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 6
- 102100033220 Xanthine oxidase Human genes 0.000 description 6
- 230000002401 inhibitory effect Effects 0.000 description 6
- AMTWCFIAVKBGOD-UHFFFAOYSA-N dioxosilane;methoxy-dimethyl-trimethylsilyloxysilane Chemical compound O=[Si]=O.CO[Si](C)(C)O[Si](C)(C)C AMTWCFIAVKBGOD-UHFFFAOYSA-N 0.000 description 5
- 229940083037 simethicone Drugs 0.000 description 5
- 229960002529 benzbromarone Drugs 0.000 description 4
- WHQCHUCQKNIQEC-UHFFFAOYSA-N benzbromarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC(Br)=C(O)C(Br)=C1 WHQCHUCQKNIQEC-UHFFFAOYSA-N 0.000 description 4
- 230000029142 excretion Effects 0.000 description 4
- -1 polydimethylsiloxane Polymers 0.000 description 4
- 238000011282 treatment Methods 0.000 description 4
- RCEAADKTGXTDOA-UHFFFAOYSA-N OS(O)(=O)=O.CCCCCCCCCCCC[Na] Chemical compound OS(O)(=O)=O.CCCCCCCCCCCC[Na] RCEAADKTGXTDOA-UHFFFAOYSA-N 0.000 description 3
- 239000003513 alkali Substances 0.000 description 3
- 229960002708 antigout preparations Drugs 0.000 description 3
- 229940008099 dimethicone Drugs 0.000 description 3
- 239000006260 foam Substances 0.000 description 3
- 239000008233 hard water Substances 0.000 description 3
- 230000001737 promoting effect Effects 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- IAKHMKGGTNLKSZ-INIZCTEOSA-N (S)-colchicine Chemical compound C1([C@@H](NC(C)=O)CC2)=CC(=O)C(OC)=CC=C1C1=C2C=C(OC)C(OC)=C1OC IAKHMKGGTNLKSZ-INIZCTEOSA-N 0.000 description 2
- 201000001431 Hyperuricemia Diseases 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000003945 anionic surfactant Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000012738 dissolution medium Substances 0.000 description 2
- 238000004945 emulsification Methods 0.000 description 2
- 238000005187 foaming Methods 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- NAFSTSRULRIERK-UHFFFAOYSA-M monosodium urate Chemical group [Na+].N1C([O-])=NC(=O)C2=C1NC(=O)N2 NAFSTSRULRIERK-UHFFFAOYSA-M 0.000 description 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 229920002545 silicone oil Polymers 0.000 description 2
- 238000005063 solubilization Methods 0.000 description 2
- 230000007928 solubilization Effects 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- 208000036487 Arthropathies Diseases 0.000 description 1
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical class [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 229940124186 Dehydrogenase inhibitor Drugs 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010023203 Joint destruction Diseases 0.000 description 1
- 208000012659 Joint disease Diseases 0.000 description 1
- 241000234479 Narcissus Species 0.000 description 1
- 102000005773 Xanthine dehydrogenase Human genes 0.000 description 1
- 108010091383 Xanthine dehydrogenase Proteins 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000006838 adverse reaction Effects 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
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 238000006065 biodegradation reaction Methods 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 229960001338 colchicine Drugs 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- GVGUFUZHNYFZLC-UHFFFAOYSA-N dodecyl benzenesulfonate;sodium Chemical compound [Na].CCCCCCCCCCCCOS(=O)(=O)C1=CC=CC=C1 GVGUFUZHNYFZLC-UHFFFAOYSA-N 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 238000011866 long-term treatment Methods 0.000 description 1
- 229940105082 medicinal charcoal Drugs 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 229960003081 probenecid Drugs 0.000 description 1
- DBABZHXKTCFAPX-UHFFFAOYSA-N probenecid Chemical compound CCCN(CCC)S(=O)(=O)C1=CC=C(C(O)=O)C=C1 DBABZHXKTCFAPX-UHFFFAOYSA-N 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 229940080264 sodium dodecylbenzenesulfonate Drugs 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
Images
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/426—1,3-Thiazoles
-
- 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
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
-
- 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
- A61K9/2031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
- A61K9/2036—Silicones; Polysiloxanes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
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- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a febuxostat tablet and a preparation method thereof, wherein the febuxostat tablet comprises the following components in parts by weight: active ingredients: 20 parts of febuxostat; auxiliary materials: 0.5-5 parts of surfactant, 0.05-0.5 part of defoamer, 62.5-67.45 parts of filler, 3 parts of adhesive, 5 parts of disintegrant, 1 part of lubricant and 3 parts of coating agent; wherein the defoaming agent is dimeticone. The beneficial effects of the invention are: by adding the surfactant sodium dodecyl sulfate with a specific mixing ratio and the dimeticone for increasing the action of the sodium dodecyl sulfate, a good solubilizing effect is obtained, and the problem of febuxostat dissolution is solved.
Description
Technical Field
The invention relates to the technical field of medicines, and particularly relates to a febuxostat tablet and a preparation method thereof.
Background
Anti-gout drugs are of a few varieties at present, and clinical treatment mainly comprises colchicine, non-steroidal anti-inflammatory drugs, hormones, drugs for promoting uric acid excretion (such as probenecid, sulpirone and benzbromarone) and drugs for inhibiting uric acid synthesis (allopurinol). Narcissus, non-steroidal anti-inflammatory drugs and hormones are mainly applied in the acute onset stage, and drugs for promoting uric acid excretion and inhibiting uric acid synthesis are mainly applied in the remission stage. These drugs have therapeutic deficiencies. Poor curative effect and great side effect become the bottleneck of clinical application.
The gout treatment drug market hardly sees new products on the market, and the market still takes allopurinol and benzbromarone as main materials. Both of these drugs are used in the remission stage, the former mainly inhibiting uric acid production and the latter mainly promoting excretion. From the onset principle of gout, the two medicines are definitely the lead products. The medicine artificial kidney-Aixite, medicinal charcoal, etc. which have been in the market but have not cured the symptoms, have gradually faded out of the view of the clinician. Because gout has low morbidity, the market investment attraction and the return rate are relatively low, more capital investment is difficult to attract to develop new generation products, and the selectable range of doctors in the aspect of clinical medication is small. Therefore, even if allopurinol and benzbromarone are not satisfactory in treatment, other choices are difficult to make, and the sales of allopurinol and benzbromarone in the gout market are still steadily increased.
Febuxostat, the chemical name of which is 2- [ (3-cyano-4-isobutoxy) phenyl ] -4-methyl-5-thiazolecarboxylic acid, is a Xanthine Oxidase (XO) inhibitor, is a new generation anti-gout drug synthesized by Teijin, is suitable for long-term treatment of hyperuricemia with gout symptoms, is crystal-related arthropathy caused by deposition of monosodium urate (MSU), is directly related to hyperuricemia caused by purine metabolic disorder and (or) reduction of uric acid excretion, and belongs to the category of metabolic rheumatism. Gout can be complicated with kidney disease, and severe cases can cause joint destruction and renal function damage, often accompanied with hyperlipidemia, hypertension, diabetes, arteriosclerosis, coronary heart disease, etc. Compared with allopurine, febuxostat has obvious advantages:
(1) Allopurinol only has an inhibiting effect on reduced XOR, and febuxostat has a remarkable inhibiting effect on oxidized and reduced XOR, so that the effect of reducing uric acid is more powerful and lasting;
(2) Since allopurinol is a purine analog, it inevitably causes effects on other enzymatic activities involved in purine and pyridine metabolism. Therefore, in allopurinol treatment, repeated large dose administration is required to maintain a high drug level. This also leads to serious and even fatal adverse reactions due to drug accumulation. And the febuxostat is a non-purine XOR inhibitor, so that the safety is better.
The recommended oral dose of febuxostat is 40mg once daily. If the serum uric acid level is more than 6 mg/dl 2 weeks after administration, 80 mg may be considered to be administered once a day. The product is recommended to be taken for at least 6 months for preventing gout attack, and the influence of food or antacid is not required to be considered when the product is taken.
Febuxostat (TMX-67, TEI-6720) is a new generation anti-gout drug synthesized by Teijin, shows excellent activity, is a selective xanthine oxidase/xanthine dehydrogenase inhibitor and has good development prospect. However, the solubility of febuxostat is relatively low, so that the pharmaceutical preparation containing febuxostat has the problems of low dissolution rate and low bioavailability.
Based on the situation, the febuxostat tablet and the preparation method thereof are provided, so that a good solubilizing effect is obtained, and the problem of febuxostat dissolution is solved.
Disclosure of Invention
The invention aims to overcome the defects of the prior art, and provides a febuxostat tablet and a preparation method thereof, wherein the febuxostat tablet can obtain a good solubilizing effect by adding medicinal lauryl sodium sulfate and dimeticone with a specific mixing ratio, and the problem of dissolution of febuxostat is solved.
The purpose of the invention is realized by the following technical scheme:
a febuxostat tablet:
the composition comprises the following components in parts by weight: active ingredients: 20 parts of febuxostat; auxiliary materials: 0.5-5 parts of surfactant, 0.05-0.5 part of defoamer, 62.5-67.45 parts of filler, 3 parts of adhesive, 5 parts of disintegrant, 1 part of lubricant and 3 parts of coating agent;
wherein the defoaming agent is dimeticone.
Further, the viscosity of the dimeticone is 100mm 2 /s～800mm 2 And(s) in the presence of a catalyst. Dimethicone (polydimethylsiloxane), which varies in kinematic viscosity depending on the molecular weight.
Further, the surfactant is medicinal sodium dodecyl sulfate.
Furthermore, the medicinal sodium dodecyl sulfate contains, by mass, not less than 80% of sodium dodecyl sulfate and not more than 20% of sodium tetradecyl sulfate.
The medicinal lauryl sodium sulfate is a mixture of lauryl sodium sulfate and tetradecyl sodium sulfate, is easy to dissolve in water, is insensitive to alkali and hard water, has emulsification and excellent foaming power, is an anionic surfactant slightly toxic to human bodies, and has a biodegradation degree of more than 90%; the sodium dodecyl benzene sulfonate has stable chemical properties to alkali, dilute acid and hard water, can establish a balance system with strong acid, and has good surface activity and strong hydrophilicity.
Further, the weight ratio of the sodium dodecyl sulfate to the dimeticone for the febuxostat tablet traditional Chinese medicine is 10:1.
the simethicone (polydimethylsiloxane) has small surface tension, good thermal stability and good chemical stability, and has the effects of breaking and inhibiting foam for the foam generated by the sodium dodecyl sulfate in the scheme, and the finding shows that in the preparation process of the febuxostat tablet, the good solubilizing effect is obtained by adding the surfactant medicinal sodium dodecyl sulfate with a specific mixing ratio and the simethicone for increasing the action of the sodium dodecyl sulfate.
Preferably, the filler is one or more of lactose, corn starch, microcrystalline cellulose.
Preferably, the disintegrant is one or more of sodium carboxymethyl starch, PVPP, croscarmellose sodium.
Further preferably, the lubricant is one or more of magnesium stearate and aerosil.
Preferably, the binder is PVPK30; the coating agent is gastric soluble coating powder.
A process for preparing febuxostat tablets comprising the steps of:
A. preparing the adhesive into a 5% aqueous solution by using purified water, adding sodium dodecyl sulfate and dimeticone, stirring and mixing to obtain a uniformly dispersed mixed solution;
B. mixing the mixed solution with the mixed filler and disintegrant, granulating by a 24-mesh wet method, drying at 50-60 ℃ until the water content is less than or equal to 3.5%, and finishing granules by a 24-mesh sieve;
C. and C, adding a lubricant into the granules obtained by the granulation in the step B, uniformly mixing, tabletting, and coating with a coating agent to obtain the non-butostat tablets, wherein the coating weight is increased by 3%.
The sodium dodecyl sulfate is easy to dissolve in water, is insensitive to alkali and hard water, has emulsification and excellent foaming power, is an anionic surfactant slightly toxic to human bodies, has good surface activity and stronger hydrophilicity; febuxostat has lower solubility, and the addition of medicinal sodium dodecyl sulfate helps to reduce the surface active tension of a solvent (such as water) so as to increase the solubility; therefore, in order to obtain a better dissolution rate, a certain amount of surfactant is added in the preparation of the febuxostat tablet; when dimethyl silicone oil (polydimethylsiloxane) with certain viscosity is added, the dimethyl silicone oil (polydimethylsiloxane) has extremely strong defoaming force, the foam generated by the sodium dodecyl sulfate can be eliminated in time, the surface activity of the sodium dodecyl sulfate is prevented from being reduced, the surface activity of the sodium dodecyl sulfate is enhanced, and the using amount of the sodium dodecyl sulfate in the tablet is correspondingly reduced.
The invention has the beneficial effects that:
the febuxostat-containing pharmaceutical preparation has the advantages that the solubility of febuxostat is low, so that the problems of low dissolution rate and low bioavailability exist, and the surfactant sodium dodecyl sulfate and the simethicone which can increase the effect of the sodium dodecyl sulfate are added according to a specific mixing ratio, so that a good solubilization effect is obtained, and the problem of febuxostat dissolution is solved.
Drawings
FIG. 1 is a comparative dissolution chart of febuxostat tablets.
Detailed Description
The technical solution of the present invention is further described in detail with reference to the following specific examples, but the scope of the present invention is not limited to the following.
Examples
Example 1
A febuxostat tablet comprises:
active ingredients:
40mg of febuxostat;
auxiliary materials:
the preparation method comprises the following steps:
(1) Preparing the adhesive into a 5% aqueous solution by using purified water, adding sodium dodecyl sulfate and dimeticone, stirring and mixing to obtain a uniformly dispersed mixed solution;
(2) Mixing the mixed solution with the mixed filler and disintegrant, granulating by a 24-mesh wet method, drying at 50-60 ℃ until the water content is less than or equal to 3.5%, and finishing granules by a 24-mesh sieve;
(3) And (3) adding a lubricant into the granules obtained by the whole granulation in the step (2), uniformly mixing, tabletting, and coating with a coating agent to obtain the non-bestatis tablets, wherein the coating weight is increased by 3%.
Example 2
The difference between the embodiment and the embodiment 1 is only that the formulation is different from the embodiment 1, and the dosage of the sodium dodecyl sulfate and the dimeticone is increased by 5 times compared with the embodiment 1 in an equal ratio.
Specifically, in this embodiment, a febuxostat tablet includes:
active ingredients:
40mg of febuxostat;
auxiliary materials:
example 3
The difference between the embodiment and the embodiment 1 is only that the formula is different from the embodiment 1, and the dosage of the sodium dodecyl sulfate and the dimeticone is increased by 10 times in an equal ratio, which is the same as that of the embodiment 1.
Specifically, in this embodiment, a febuxostat tablet includes:
active ingredients: 40mg of febuxostat;
auxiliary materials:
comparative example
Weighing the components by weight shown in Table 1 to design comparative example 1, comparative example 2 and comparative example 3;
and preparing febuxostat tablets according to the following steps:
step a, preparing 5% aqueous solution of PVPK30 by using purified water, adding sodium dodecyl sulfate, stirring, mixing and dispersing uniformly;
step b, mixing the mixed solution prepared in the step a with the mixed filler and disintegrant, performing wet granulation by using a 24-mesh sieve, drying at 50-60 ℃ until the water content is less than or equal to 3.5%, and performing granulation by using the 24-mesh sieve;
and c, adding a lubricant into the granules prepared in the step b for tabletting, and then coating with a coating agent to obtain the finished product, wherein the coating weight is increased by 3%.
Table 1 formula table
Dissolution rates of the samples of the original ground, example 1, example 2, example 3, comparative example 1, comparative example 2 and comparative example 3 in the dissolution medium of pH6.0 were respectively tested, and the test results are shown in Table 2.
TABLE 2 dissolution results of dissolution media pH6.0 from the original research and inventive examples
The dissolution comparison graphs of example 1, example 2, example 3, comparative example 1, comparative example 2, comparative example 3, and the original sample are plotted as shown in fig. 1.
The above experimental results demonstrate that:
(1) The dissolution effects of the examples 1, 2 and 3 are consistent with those of the original drug, which shows that the combination of sodium dodecyl sulfate and dimethicone has obvious solubilization effect, but the double increase of the combined dosage does not generate double effect, which shows that the combination of sodium dodecyl sulfate and dimethicone has good effect when small amount.
(2) The speed and the degree of dissolution of the drug in the comparative example 1 are obviously inferior to those in the example 1, which shows that the effect of only adding the sodium dodecyl sulfate and not adding the dimeticone is much worse than that of adding the sodium dodecyl sulfate and the dimeticone in a specific ratio;
(3) The speed and degree of dissolution of the drug of comparative example 2 are obviously inferior to those of example 2, and the speed and degree of dissolution of the drug of comparative example 2 are obviously inferior to those of example 1, which shows that even though the dosage of sodium dodecyl sulfate is increased by times (5 times), the effect of adding sodium dodecyl sulfate without simethicone is much worse than that of adding the sodium dodecyl sulfate and simethicone in a specific ratio;
(4) Comparative example 3 although the speed and degree of drug dissolution are not much different from those of example 2, the dosage of the sodium dodecyl sulfate reaches 5%, which has obvious influence on the hardness and friability of the febuxostat tablets, increases the difficulty of production control, and seriously influences the production yield and the quality uniformity among product batches.
Therefore, the combination of the sodium dodecyl sulfate and the dimeticone is adopted in the invention, and the febuxostat is unexpectedly promoted to dissolve out.
In the present invention, the gastric coating powder provided by Carlekang is used as the gastric coating powder.
The foregoing is illustrative of the preferred embodiments of this invention, and it is to be understood that the invention is not limited to the precise form disclosed herein and that various other combinations, modifications, and environments may be resorted to, falling within the scope of the concept as disclosed herein, either as described above or as apparent to those skilled in the relevant art. And that modifications and variations may be effected by those skilled in the art without departing from the spirit and scope of the invention as defined by the appended claims.
Claims (10)
1. A febuxostat tablet is characterized in that:
the composition comprises the following components in parts by weight:
active ingredients: 20 parts of febuxostat;
auxiliary materials: 0.5-5 parts of surfactant, 0.05-0.5 part of defoaming agent, 62.5-67.45 parts of filler, 3 parts of adhesive, 5 parts of disintegrating agent, 1 part of lubricant and 3 parts of coating agent;
wherein the defoaming agent is dimeticone.
2. The febuxostat tablet according to claim 1, wherein the viscosity of the dimeticone is 100mm 2/s-800 mm2/s.
3. The febuxostat tablet according to claim 2, wherein the surfactant is medicinal sodium lauryl sulfate.
4. The febuxostat tablet according to claim 3, wherein the medicinal sodium dodecyl sulfate contains more than or equal to 80% of sodium dodecyl sulfate and less than or equal to 20% of sodium tetradecyl sulfate in percentage by mass.
5. The febuxostat tablet according to claim 4, wherein the weight ratio of sodium dodecyl sulfate to dimeticone for the febuxostat tablet traditional Chinese medicine is 10:1.
6. the febuxostat tablet according to claim 5, wherein the filler is one or more of lactose, corn starch and microcrystalline cellulose.
7. The febuxostat tablet according to claim 6, wherein the disintegrant is one or more of sodium carboxymethyl starch, PVPP and croscarmellose sodium.
8. The febuxostat tablet according to claim 7, wherein the lubricant is one or more of magnesium stearate and aerosil.
9. The febuxostat tablet according to claim 8, wherein the binder is PVPK30; the coating agent is gastric soluble coating powder.
10. A process for preparing the febuxostat tablet according to any one of claims 1 to 9, comprising the steps of:
A. preparing the adhesive into a 5% aqueous solution by using purified water, adding sodium dodecyl sulfate and dimeticone, stirring and mixing to obtain a uniformly dispersed mixed solution;
B. mixing the mixed solution with the mixed filler and disintegrant, granulating by a 24-mesh wet method, drying at 50-60 ℃ until the water content is less than or equal to 3.5%, and finishing granules by a 24-mesh sieve;
C. and C, adding a lubricant into the granules obtained by the granulation in the step B, uniformly mixing, tabletting, and coating with a coating agent to obtain the non-butostat tablets, wherein the coating weight is increased by 3%.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2012097019A (en) * | 2010-11-01 | 2012-05-24 | Hoyu Co Ltd | Hair cosmetic composition, method for using the same, and hair cosmetic product |
| CN105434400A (en) * | 2015-12-24 | 2016-03-30 | 寿光富康制药有限公司 | Preparation method of tiny proton pump inhibitor enteric-coated pellet |
| CN108283626A (en) * | 2018-02-06 | 2018-07-17 | 江苏长泰药业有限公司 | A kind of film of blocking drugs release and its preparation |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2012097019A (en) * | 2010-11-01 | 2012-05-24 | Hoyu Co Ltd | Hair cosmetic composition, method for using the same, and hair cosmetic product |
| CN105434400A (en) * | 2015-12-24 | 2016-03-30 | 寿光富康制药有限公司 | Preparation method of tiny proton pump inhibitor enteric-coated pellet |
| CN108283626A (en) * | 2018-02-06 | 2018-07-17 | 江苏长泰药业有限公司 | A kind of film of blocking drugs release and its preparation |
Non-Patent Citations (1)
| Title |
|---|
| 李伊娜等: "往复筒法在药物溶出度研究中的应用进展", 药物分析杂志, vol. 41, no. 2, pages 188 * |
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Inventor after: Xiao Shiyuan Inventor after: Li Rui Inventor after: Gu Weilin Inventor after: Wei Wei Inventor after: Yang Jie Inventor after: Chen Wen Inventor after: Mou Deli Inventor after: Shen Hua Inventor after: Zhang Yu Inventor after: Han Pengcen Inventor after: Liu Hui Inventor after: Zhu Deqi Inventor after: Zeng Yunyi Inventor after: Xiao Bo Inventor after: Gan Rui Inventor before: Xiao Shiyuan Inventor before: Li Rui Inventor before: Gu Weilin Inventor before: Wei Wei Inventor before: Yang Jie Inventor before: Chen Wen Inventor before: Mou Deli Inventor before: Shen Hua Inventor before: Zhang Yu Inventor before: Han Pengcen Inventor before: Liu Hui Inventor before: Zhu Deqi Inventor before: Zeng Yunyi Inventor before: Xiao Bo Inventor before: Gan Rui |