CN116251067B - Fluconazole tablet, preparation method and application - Google Patents
Fluconazole tablet, preparation method and application Download PDFInfo
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- CN116251067B CN116251067B CN202310439079.7A CN202310439079A CN116251067B CN 116251067 B CN116251067 B CN 116251067B CN 202310439079 A CN202310439079 A CN 202310439079A CN 116251067 B CN116251067 B CN 116251067B
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- RFHAOTPXVQNOHP-UHFFFAOYSA-N fluconazole Chemical compound C1=NC=NN1CC(C=1C(=CC(F)=CC=1)F)(O)CN1C=NC=N1 RFHAOTPXVQNOHP-UHFFFAOYSA-N 0.000 title claims abstract description 112
- 229960004884 fluconazole Drugs 0.000 title claims abstract description 112
- 238000002360 preparation method Methods 0.000 title abstract description 21
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims abstract description 29
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims abstract description 22
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims abstract description 22
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims abstract description 22
- 239000008108 microcrystalline cellulose Substances 0.000 claims abstract description 22
- 229940016286 microcrystalline cellulose Drugs 0.000 claims abstract description 22
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 claims abstract description 20
- 229920000609 methyl cellulose Polymers 0.000 claims abstract description 20
- 239000001923 methylcellulose Substances 0.000 claims abstract description 20
- 235000010981 methylcellulose Nutrition 0.000 claims abstract description 20
- 239000011248 coating agent Substances 0.000 claims description 10
- 238000000576 coating method Methods 0.000 claims description 10
- 239000000741 silica gel Substances 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 6
- 239000001508 potassium citrate Substances 0.000 claims description 6
- 229960002635 potassium citrate Drugs 0.000 claims description 6
- QEEAPRPFLLJWCF-UHFFFAOYSA-K potassium citrate (anhydrous) Chemical compound [K+].[K+].[K+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O QEEAPRPFLLJWCF-UHFFFAOYSA-K 0.000 claims description 6
- 235000011082 potassium citrates Nutrition 0.000 claims description 6
- 239000000843 powder Substances 0.000 claims description 6
- 239000001509 sodium citrate Substances 0.000 claims description 6
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical group O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 claims description 6
- 239000007888 film coating Substances 0.000 claims description 5
- 238000009501 film coating Methods 0.000 claims description 5
- 229910002027 silica gel Inorganic materials 0.000 claims description 5
- 230000004584 weight gain Effects 0.000 claims description 5
- 235000019786 weight gain Nutrition 0.000 claims description 5
- 229910021487 silica fume Inorganic materials 0.000 claims 3
- 238000007907 direct compression Methods 0.000 claims 1
- 239000012535 impurity Substances 0.000 abstract description 16
- 229960002900 methylcellulose Drugs 0.000 abstract description 16
- 238000002156 mixing Methods 0.000 abstract description 16
- 239000000126 substance Substances 0.000 abstract description 14
- 229910002012 Aerosil® Inorganic materials 0.000 abstract description 12
- 230000001133 acceleration Effects 0.000 abstract description 10
- 230000000694 effects Effects 0.000 abstract description 4
- 239000000463 material Substances 0.000 abstract description 3
- 239000003795 chemical substances by application Substances 0.000 abstract description 2
- 229940001468 citrate Drugs 0.000 abstract description 2
- 239000000825 pharmaceutical preparation Substances 0.000 abstract description 2
- 230000002195 synergetic effect Effects 0.000 abstract description 2
- 239000003826 tablet Substances 0.000 description 68
- 230000000052 comparative effect Effects 0.000 description 16
- 239000000243 solution Substances 0.000 description 15
- 238000007873 sieving Methods 0.000 description 14
- 238000004090 dissolution Methods 0.000 description 11
- 238000010298 pulverizing process Methods 0.000 description 10
- 239000000203 mixture Substances 0.000 description 5
- 229940079593 drug Drugs 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 206010046914 Vaginal infection Diseases 0.000 description 3
- 201000008100 Vaginitis Diseases 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 230000014759 maintenance of location Effects 0.000 description 3
- 239000012488 sample solution Substances 0.000 description 3
- 230000035945 sensitivity Effects 0.000 description 3
- 238000012795 verification Methods 0.000 description 3
- 239000003429 antifungal agent Substances 0.000 description 2
- 239000007919 dispersible tablet Substances 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 230000000306 recurrent effect Effects 0.000 description 2
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 208000004746 Atrophic Vaginitis Diseases 0.000 description 1
- 206010003693 Atrophic vulvovaginitis Diseases 0.000 description 1
- 208000004926 Bacterial Vaginosis Diseases 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- 208000004483 Dyspareunia Diseases 0.000 description 1
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 1
- 206010017533 Fungal infection Diseases 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- 208000007074 Trichomonas Vaginitis Diseases 0.000 description 1
- 208000025206 Trichomonas vaginitis urogenital infection Diseases 0.000 description 1
- 208000037009 Vaginitis bacterial Diseases 0.000 description 1
- 201000007096 Vulvovaginal Candidiasis Diseases 0.000 description 1
- 206010067641 Vulvovaginal burning sensation Diseases 0.000 description 1
- 206010056530 Vulvovaginal pruritus Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 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 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 235000019658 bitter taste Nutrition 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 210000003756 cervix mucus Anatomy 0.000 description 1
- 229960001681 croscarmellose sodium Drugs 0.000 description 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 206010013990 dysuria Diseases 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000035558 fertility Effects 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 208000024386 fungal infectious disease Diseases 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000027939 micturition Effects 0.000 description 1
- YTJSFYQNRXLOIC-UHFFFAOYSA-N octadecylsilane Chemical compound CCCCCCCCCCCCCCCCCC[SiH3] YTJSFYQNRXLOIC-UHFFFAOYSA-N 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 201000010808 postmenopausal atrophic vaginitis Diseases 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 229910052611 pyroxene Inorganic materials 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000013558 reference substance Substances 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000012085 test solution Substances 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- 208000010484 vulvovaginitis Diseases 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
- A61K9/2004—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
- 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
- A61K31/4196—1,2,4-Triazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to a fluconazole tablet, a preparation method and application thereof. The fluconazole tablet according to the invention comprises: fluconazole, citrate, microcrystalline cellulose, methylcellulose, low-substituted hydroxypropyl cellulose and aerosil. Through optimizing auxiliary materials and proportion, particularly adding citrate and fluconazole for blending, the effect of a synergistic disintegrating agent is achieved, the rapid disintegration of the fluconazole tablet is promoted, and the disintegration time is shortened; secondly, the problem that the content of relevant substances of the fluconazole tablet is higher is solved, the total impurity content of the fluconazole tablet is lower and basically kept unchanged in an acceleration test, and the stability is high.
Description
Technical Field
The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to a fluconazole tablet, a preparation method and application thereof.
Background
Vaginitis is a common gynaecological disease, which can be caused by infection of various pathogens, and is also related to external stimulus, hormone level and the like. It is mainly manifested by abnormal vaginal secretion, vaginal itching or burning sensation, and can be accompanied by symptoms such as frequent urination, painful urination, dyspareunia and the like. The disease has recurrent attacks, and if the disease is not diagnosed in time, the female fertility, life and health are seriously affected. Clinically common vaginitis types include trichomonas vaginitis, vulvovaginal candida mycosis, bacterial vaginosis, atrophic vaginitis, infant vulvovaginitis and the like.
Fluconazole is a triazole antifungal drug which is developed by the company of pyroxene, is marketed in denmark, france, irish and uk in 1988, is approved by the FDA in the united states in 1990, is a broad-spectrum antifungal drug, and can treat acute or recurrent mycotic vaginitis. The preparation formulations sold in the market at present comprise tablets, capsules, powder injection and injection.
Chinese patent publication No. CN103751132a discloses a fluconazole dispersible tablet and a preparation method thereof, which is to highly disperse fluconazole in a dispersant of one of microcrystalline cellulose and kaolin, effectively mask the bitter taste of fluconazole, and have reliable release behavior. Theoretically, the dispersible tablet should have a rapid dissolution rate and a disintegration time of 3 minutes, and a dissolution rate of 93% at 45 minutes is slow, compared to a tablet.
The Chinese patent with publication number CN108578377A discloses a fluconazole tablet and a preparation method thereof, wherein the tablet comprises the following raw materials in parts by weight: 40-50 parts of fluconazole, 15-40 parts of filler (sodium alginate, microcrystalline cellulose and anhydrous calcium hydrophosphate), 2-15 parts of disintegrant croscarmellose sodium, 30-10 parts of adhesive povidone K and 0.2-2 parts of lubricant magnesium stearate, thus shortening the disintegration time and improving the dissolution rate, but the total impurities of related substances in an acceleration test reach 0.44 percent, and the friability is relatively high.
In different prior art, the problems of slow dissolution, long disintegration time, high friability, high impurity content and the like of the fluconazole tablet exist, so a technical scheme is needed to solve all the problems and provide a high-quality fluconazole tablet.
Disclosure of Invention
The invention provides a fluconazole tablet with rapid dissolution, rapid disintegration, low friability and low impurity content, which solves the problems of slow dissolution, long limit of disintegration, high friability, high impurity content and the like of the fluconazole tablet by adding optimized auxiliary materials, especially citrate.
Specifically, the technical scheme of the invention is as follows:
the invention provides a fluconazole tablet, which comprises the following components: fluconazole, citrate, microcrystalline cellulose, methylcellulose, low-substituted hydroxypropyl cellulose and aerosil.
In a plurality of embodiments, the fluconazole tablet comprises the following components in percentage by weight:
in one embodiment, the fluconazole tablet comprises the following components in percentage by weight:
in one embodiment, the fluconazole tablet comprises the following components in percentage by weight:
in one embodiment, the fluconazole tablet comprises the following components in percentage by weight:
further, the citrate is sodium citrate or/and potassium citrate, namely the citrate is sodium citrate, the citrate is potassium citrate, and the citrate is a mixture of sodium citrate and potassium citrate.
It should be noted that, the embodiment of the present invention in which the citrate is a mixture of sodium citrate and potassium citrate also makes experiments within the above weight parts, that is, the mixture of sodium citrate and potassium citrate has the same or similar technical effects as other embodiments in the specification, and the effects are not listed here.
Further, the fluconazole tablets may be further coated with a film coating premix, in various embodiments, the coating weight gain is between 1.5% and 4.0%, in one embodiment, the coating weight gain is 2.5%.
Furthermore, the fluconazole tablet is prepared by adopting a direct tabletting method, the method avoids the granulating process, has reduced working procedures, can save time and energy, and avoids the factors of temperature and moisture which are unfavorable for medicines.
The second object of the invention is to provide an application of the fluconazole tablet in preparing antifungal medicines.
Compared with the prior art, the invention has the beneficial effects that:
The invention prefers auxiliary materials and proportion, especially the citrate and fluconazole are added for blending, which firstly plays a role of a synergistic disintegrating agent, promotes the rapid disintegration of the fluconazole tablet and shortens the disintegration time; secondly, the problem that the content of relevant substances of the fluconazole tablet is higher is solved, the total impurity content of the fluconazole tablet is lower, basically does not increase and has high stability in an acceleration test.
Drawings
Fig. 1: acceleration test, total impurity content curve of example 1, comparative examples 1-3, commercially available fluconazole tablets;
fig. 2: acceleration test, total impurity profile for example 2, 3, 6, 8, 10 fluconazole tablets.
Detailed Description
The present invention will be further described with reference to examples for the purpose of making the objects and technical aspects of the present invention more apparent, but the scope of the present invention is not limited to these examples, which are only for explaining the present invention. It will be understood by those skilled in the art that variations or equivalent substitutions that do not depart from the spirit of the invention are intended to be included within the scope of the invention.
EXAMPLE 1 fluconazole tablet
The formula comprises the following components:
The preparation method comprises the following steps:
Pulverizing fluconazole and citrate, sieving, adding microcrystalline cellulose, methylcellulose, low-substituted hydroxypropyl cellulose, and aerosil, mixing, and tabletting.
EXAMPLE 2 fluconazole tablet
The formula comprises the following components:
The preparation method comprises the following steps:
Pulverizing fluconazole and citrate, sieving, adding microcrystalline cellulose, methylcellulose, low-substituted hydroxypropyl cellulose, and aerosil, mixing, and tabletting.
EXAMPLE 3 fluconazole tablet
The formula comprises the following components:
The preparation method comprises the following steps:
Pulverizing fluconazole and citrate, sieving, adding microcrystalline cellulose, methylcellulose, low-substituted hydroxypropyl cellulose, and aerosil, mixing, and tabletting.
EXAMPLE 4 fluconazole tablet
The formula comprises the following components:
The preparation method comprises the following steps:
Pulverizing fluconazole and citrate, sieving, adding microcrystalline cellulose, methylcellulose, low-substituted hydroxypropyl cellulose, and aerosil, mixing, and tabletting.
EXAMPLE 5 fluconazole tablet
The formula comprises the following components:
The preparation method comprises the following steps:
Pulverizing fluconazole and citrate, sieving, adding microcrystalline cellulose, methylcellulose, low-substituted hydroxypropyl cellulose, and aerosil, mixing, and tabletting.
EXAMPLE 6 fluconazole tablet
The formula comprises the following components:
The preparation method comprises the following steps:
Pulverizing fluconazole and citrate, sieving, adding microcrystalline cellulose, methylcellulose, low-substituted hydroxypropyl cellulose, and aerosil, mixing, and tabletting.
EXAMPLE 7 fluconazole tablet
The formula comprises the following components:
The preparation method comprises the following steps:
And (3) properly crushing and sieving fluconazole and citrate, adding crushed and sieved microcrystalline cellulose, methylcellulose, low-substituted hydroxypropyl cellulose and micro-powder silica gel, mixing, tabletting, coating the film coating premix, and obtaining the fluconazole tablet with the coating weight gain of 1.5%.
EXAMPLE 8 fluconazole tablet
The formula comprises the following components:
The preparation method comprises the following steps:
And (3) properly crushing and sieving fluconazole and citrate, adding crushed and sieved microcrystalline cellulose, methylcellulose, low-substituted hydroxypropyl cellulose and micro-powder silica gel, mixing, tabletting, coating the film coating premix, and increasing the weight of the coating by 2.5 percent to obtain the fluconazole tablet.
EXAMPLE 9 fluconazole tablet
The formula comprises the following components:
The preparation method comprises the following steps:
And (3) properly crushing and sieving fluconazole and citrate, adding crushed and sieved microcrystalline cellulose, methylcellulose, low-substituted hydroxypropyl cellulose and micro-powder silica gel, mixing, tabletting, coating the film coating premix, and coating the mixture to gain the weight by 4.0 percent, thus obtaining the fluconazole tablet.
EXAMPLE 10 fluconazole tablet
The formula comprises the following components:
The preparation method comprises the following steps:
Pulverizing fluconazole and citrate, sieving, adding microcrystalline cellulose, methylcellulose, low-substituted hydroxypropyl cellulose, and aerosil, mixing, and tabletting.
EXAMPLE 11 fluconazole tablet
The formula comprises the following components:
The preparation method comprises the following steps:
Pulverizing fluconazole and citrate, sieving, adding microcrystalline cellulose, methylcellulose, low-substituted hydroxypropyl cellulose, and aerosil, mixing, and tabletting.
Comparative example 1 fluconazole tablet
The formula comprises the following components:
The preparation method comprises the following steps:
And (3) properly crushing and sieving fluconazole, adding crushed and sieved microcrystalline cellulose, methylcellulose, low-substituted hydroxypropyl cellulose and micro powder silica gel, mixing, and tabletting to obtain the fluconazole tablet.
Comparative example 2 fluconazole tablet
The formula comprises the following components:
The preparation method comprises the following steps:
Pulverizing fluconazole and citrate, sieving, adding microcrystalline cellulose, methylcellulose, low-substituted hydroxypropyl cellulose, and aerosil, mixing, and tabletting.
Comparative example 3 fluconazole tablet
The formula comprises the following components:
The preparation method comprises the following steps:
Pulverizing fluconazole and citrate, sieving, adding microcrystalline cellulose, methylcellulose, low-substituted hydroxypropyl cellulose, and aerosil, mixing, and tabletting.
Verification embodiment
1. Examples and comparative examples demonstration of the friability and hardness of fluconazole tablets
Acceleration test: the fluconazole tablets of examples and comparative examples and commercially available fluconazole tablets (national drug standard H19990151) are used as test substances, and are placed for 6 months under the conditions of the temperature of 40+/-2 ℃ and the relative humidity of 75+/-5%, and are sampled at the end of the 0 th month and the 6 th month of the test period, so that the hardness and friability of the fluconazole tablets are tested.
Table 1 friability, hardness of example and comparative example fluconazole tablets
Table 1 shows that the fluconazole tablets prepared in the examples of the invention have moderate hardness, basically no moisture absorption and softening of the tablets after the accelerated test, low friability, basically unchanged friability at the end of 6 months of the accelerated test and high physical stability, and the friability and hardness of the fluconazole tablets prepared in the comparative example and the commercial fluconazole tablets are measured.
2. Examples and comparative examples verification of substance aspects of fluconazole tablets
Acceleration test: the fluconazole tablets of the examples and the comparative examples and the commercially available fluconazole tablets (national drug standard H19990151) are used as test substances, the test substances are placed for 6 months under the conditions of the temperature of 40+/-2 ℃ and the relative humidity of 75+/-5%, and the test substances are sampled at the ends of 1 st month, 2 months, 3 months and 6 months respectively, so that the content of the related substances is detected, and a change curve of the content of the related substances is drawn.
The related substances are measured according to high performance liquid chromatography (general rule 0512). Test solution: the product is taken to be a proper amount, and is dissolved and diluted by a mobile phase to prepare a solution with the concentration of about 10mg in each 1 ml. Control solution: the sample solution was measured precisely and diluted quantitatively with the mobile phase to give a solution containing about 50. Mu.g per 1 ml. System applicability solution: taking proper amounts of fluconazole and the impurity I reference substances, adding a mobile phase for dissolving and diluting to prepare solutions with the concentration of about 1mg and 0.1mg in each 1 ml. Sensitivity solution: a suitable amount of control solution was taken and diluted with mobile phase to give a solution containing approximately 5. Mu.g per 1 ml. Chromatographic conditions: octadecylsilane chemically bonded silica is used as filler (4.6mm.times.250 mm,5 μm or column with equivalent performance); acetonitrile-0.063% ammonium formate solution (20:80) is used as mobile phase; column temperature is 40 ℃; the detection wavelength is 260nm; the sample volume was 20. Mu.l. System applicability requirements: in the system applicability solution chromatogram, the retention time of fluorine Kangfeng is about 10 minutes, and the separation degree between the impurity I peak (relative retention time is about 0.9) and the fluconazole peak is required to be satisfactory. In the sensitivity solution chromatogram, the signal to noise ratio of the peak height of the main component peak is larger than 5. Assay: precisely measuring the sample solution and the control solution, respectively injecting into a liquid chromatograph, and recording the chromatogram till 3 times of the retention time of the main component peak. Limit: the chromatogram of the sample solution contains impurity peaks, the area of each impurity peak is not larger than the main peak area (0.5%) of the control solution, the sum of the areas of each impurity peak is not larger than 2 times (1.0%) of the main peak area of the control solution, and the peaks smaller than the main peak area of the sensitivity solution are ignored.
As shown in the change curves of the total impurity content of relevant substances in the examples of figures 1-2 and the comparative examples of the fluconazole tablets and the commercially available fluconazole tablets in the acceleration test, the fluconazole tablets prepared in the embodiment of the invention are high in stability, the content of the relevant substances is low, and the total impurity content is basically unchanged along with the time of the acceleration test. In addition, other embodiments of the invention or the technical schemes within the scope of the claims also carry out related substance changes of the acceleration test, which can achieve the same or similar technical effects, and the total impurity content is lower than that of the comparative example and the commercially available fluconazole tablet.
3. Examples and comparative examples verification of fluconazole tablets with respect to disintegration and dissolution
The disintegration time and dissolution rate of the example fluconazole tablets, the comparative example fluconazole tablets and the commercially available fluconazole tablets were checked according to the method of the Chinese pharmacopoeia.
Table 2 disintegration time and dissolution rate of example fluconazole tablet, comparative example fluconazole tablet, commercially available fluconazole tablet
Table 2 shows the disintegration time and dissolution rate of the fluconazole tablets of example, comparative example and commercially available fluconazole tablets, showing that the fluconazole tablets of the present invention disintegrate rapidly, demonstrating that the citrate plays a role in promoting tablet disintegration and simultaneously makes dissolution rapid.
Claims (8)
1. The fluconazole tablet is characterized in that the fluconazole tablet comprises the following components in percentage by weight:
fluconazole 5 parts
0.1 To 0.5 part of citrate
20-50 Parts of microcrystalline cellulose
0.5-3 Parts of methyl cellulose
1-4 Parts of low-substituted hydroxypropyl cellulose
0.1-0.5 Part of micro silica gel
The citrate is sodium citrate or/and potassium citrate.
2. The fluconazole tablet according to claim 1, wherein the weight ratio of each component in said fluconazole tablet is:
fluconazole 5 parts
Citrate 0.2 parts
Microcrystalline cellulose 35 parts
Methylcellulose 1 part
2 Parts of low-substituted hydroxypropyl cellulose
0.2 Parts of micro silica gel.
3. The fluconazole tablet according to claim 1, wherein the weight ratio of each component in said fluconazole tablet is:
fluconazole 5 parts
Citrate 0.25 parts
Microcrystalline cellulose 25 parts
Methylcellulose 2 parts
2.5 Parts of low-substituted hydroxypropyl cellulose
0.3 Parts of micro powder silica gel.
4. The fluconazole tablet according to claim 1, wherein the weight ratio of each component in said fluconazole tablet is:
fluconazole 5 parts
Citrate 0.3 parts
Microcrystalline cellulose 45 parts
Methylcellulose 2.5 parts
3 Parts of low-substituted hydroxypropyl cellulose
0.4 Parts of micro silica gel.
5. The fluconazole tablet according to claim 1, wherein said fluconazole tablet is further coated with a film coating premix.
6. The fluconazole tablet according to claim 5, wherein said coating weight gain is 1.5% -4.0%.
7. The fluconazole tablet according to claim 5, wherein said coating weight gain is 2.5%.
8. The fluconazole tablet according to claim 1, wherein said fluconazole tablet is prepared by a direct compression method.
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