CN113712926A - Sildenafil orally disintegrating tablet - Google Patents
Sildenafil orally disintegrating tablet Download PDFInfo
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- CN113712926A CN113712926A CN202111010556.5A CN202111010556A CN113712926A CN 113712926 A CN113712926 A CN 113712926A CN 202111010556 A CN202111010556 A CN 202111010556A CN 113712926 A CN113712926 A CN 113712926A
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- China
- Prior art keywords
- sildenafil
- orally disintegrating
- mixture
- disintegrating tablet
- ferulic acid
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- 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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- BNRNXUUZRGQAQC-UHFFFAOYSA-N sildenafil Chemical compound CCCC1=NN(C)C(C(N2)=O)=C1N=C2C(C(=CC=1)OCC)=CC=1S(=O)(=O)N1CCN(C)CC1 BNRNXUUZRGQAQC-UHFFFAOYSA-N 0.000 title claims abstract description 66
- 229960003310 sildenafil Drugs 0.000 title claims abstract description 33
- 239000006191 orally-disintegrating tablet Substances 0.000 title claims abstract description 22
- KSEBMYQBYZTDHS-HWKANZROSA-M (E)-Ferulic acid Natural products COC1=CC(\C=C\C([O-])=O)=CC=C1O KSEBMYQBYZTDHS-HWKANZROSA-M 0.000 claims abstract description 26
- KSEBMYQBYZTDHS-HWKANZROSA-N ferulic acid Chemical group COC1=CC(\C=C\C(O)=O)=CC=C1O KSEBMYQBYZTDHS-HWKANZROSA-N 0.000 claims abstract description 26
- 229940114124 ferulic acid Drugs 0.000 claims abstract description 26
- KSEBMYQBYZTDHS-UHFFFAOYSA-N ferulic acid Natural products COC1=CC(C=CC(O)=O)=CC=C1O KSEBMYQBYZTDHS-UHFFFAOYSA-N 0.000 claims abstract description 26
- 235000001785 ferulic acid Nutrition 0.000 claims abstract description 26
- 229960002639 sildenafil citrate Drugs 0.000 claims abstract description 26
- DEIYFTQMQPDXOT-UHFFFAOYSA-N sildenafil citrate Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.CCCC1=NN(C)C(C(N2)=O)=C1N=C2C(C(=CC=1)OCC)=CC=1S(=O)(=O)N1CCN(C)CC1 DEIYFTQMQPDXOT-UHFFFAOYSA-N 0.000 claims abstract description 26
- QURCVMIEKCOAJU-UHFFFAOYSA-N trans-isoferulic acid Natural products COC1=CC=C(C=CC(O)=O)C=C1O QURCVMIEKCOAJU-UHFFFAOYSA-N 0.000 claims abstract description 26
- 229920002785 Croscarmellose sodium Polymers 0.000 claims abstract description 21
- 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 abstract description 21
- 229930195725 Mannitol Natural products 0.000 claims abstract description 21
- 229920003081 Povidone K 30 Polymers 0.000 claims abstract description 21
- 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 abstract description 21
- 229960001681 croscarmellose sodium Drugs 0.000 claims abstract description 21
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims abstract description 21
- 239000000594 mannitol Substances 0.000 claims abstract description 21
- 235000010355 mannitol Nutrition 0.000 claims abstract description 21
- 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 abstract description 21
- 238000002360 preparation method Methods 0.000 claims abstract description 14
- 239000006068 taste-masking agent Substances 0.000 claims abstract description 4
- 239000000203 mixture Substances 0.000 claims description 40
- 239000000463 material Substances 0.000 claims description 30
- 238000002156 mixing Methods 0.000 claims description 20
- 238000003756 stirring Methods 0.000 claims description 20
- 229960001855 mannitol Drugs 0.000 claims description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 11
- 238000001035 drying Methods 0.000 claims description 10
- 239000008213 purified water Substances 0.000 claims description 10
- 238000007873 sieving Methods 0.000 claims description 10
- 235000019640 taste Nutrition 0.000 abstract description 14
- 230000000873 masking effect Effects 0.000 abstract description 7
- 238000004519 manufacturing process Methods 0.000 abstract description 6
- 238000000034 method Methods 0.000 abstract description 4
- 239000003814 drug Substances 0.000 abstract description 3
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 14
- 239000003826 tablet Substances 0.000 description 10
- 235000019658 bitter taste Nutrition 0.000 description 9
- ZOOGRGPOEVQQDX-KHLHZJAASA-N cyclic guanosine monophosphate Chemical compound C([C@H]1O2)O[P@](O)(=O)O[C@@H]1[C@H](O)[C@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-KHLHZJAASA-N 0.000 description 6
- 239000000243 solution Substances 0.000 description 5
- 210000005226 corpus cavernosum Anatomy 0.000 description 4
- 239000012086 standard solution Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 3
- 230000001568 sexual effect Effects 0.000 description 3
- 230000000638 stimulation Effects 0.000 description 3
- 101100296726 Caenorhabditis elegans pde-5 gene Proteins 0.000 description 2
- 206010013911 Dysgeusia Diseases 0.000 description 2
- 208000010228 Erectile Dysfunction Diseases 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 102000011016 Type 5 Cyclic Nucleotide Phosphodiesterases Human genes 0.000 description 2
- 108010037581 Type 5 Cyclic Nucleotide Phosphodiesterases Proteins 0.000 description 2
- 229960005164 acesulfame Drugs 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 230000005496 eutectics Effects 0.000 description 2
- 201000001881 impotence Diseases 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 208000002815 pulmonary hypertension Diseases 0.000 description 2
- 239000012488 sample solution Substances 0.000 description 2
- 210000002460 smooth muscle Anatomy 0.000 description 2
- 108010011485 Aspartame Proteins 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 208000019505 Deglutition disease Diseases 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 101100189582 Dictyostelium discoideum pdeD gene Proteins 0.000 description 1
- 108010078321 Guanylate Cyclase Proteins 0.000 description 1
- 102000014469 Guanylate cyclase Human genes 0.000 description 1
- 101150098694 PDE5A gene Proteins 0.000 description 1
- 229940124639 Selective inhibitor Drugs 0.000 description 1
- 239000004376 Sucralose Substances 0.000 description 1
- YGCFIWIQZPHFLU-UHFFFAOYSA-N acesulfame Chemical compound CC1=CC(=O)NS(=O)(=O)O1 YGCFIWIQZPHFLU-UHFFFAOYSA-N 0.000 description 1
- 229960004998 acesulfame potassium Drugs 0.000 description 1
- 239000000619 acesulfame-K Substances 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- 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 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- 235000019606 astringent taste Nutrition 0.000 description 1
- 102100029175 cGMP-specific 3',5'-cyclic phosphodiesterase Human genes 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- FEWJPZIEWOKRBE-LWMBPPNESA-N levotartaric acid Chemical compound OC(=O)[C@@H](O)[C@H](O)C(O)=O FEWJPZIEWOKRBE-LWMBPPNESA-N 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000018052 penile erection Effects 0.000 description 1
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
- 230000008288 physiological mechanism Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 1
- 239000012088 reference solution Substances 0.000 description 1
- 239000013558 reference substance Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 229940126586 small molecule drug Drugs 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 235000019408 sucralose Nutrition 0.000 description 1
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 description 1
- 235000019605 sweet taste sensations Nutrition 0.000 description 1
- 239000000892 thaumatin Substances 0.000 description 1
- 235000010436 thaumatin Nutrition 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
- A61K9/2004—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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
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- Medicinal Chemistry (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Endocrinology (AREA)
- Gynecology & Obstetrics (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
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- Reproductive Health (AREA)
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- Nutrition Science (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a sildenafil orally disintegrating tablet and a preparation method thereof, belonging to the new technical field of medicine preparation. The method is realized by the following technical scheme: an orally disintegrating tablet of sildenafil, wherein the taste-masking agent is ferulic acid; the sildenafil orally disintegrating tablet comprises 0.3 to 1 mass percent of ferulic acid; preferably, the sildenafil orally disintegrating tablet comprises 14 to 46 mass percent of sildenafil citrate, 44 to 70 mass percent of mannitol, 5 to 10 mass percent of povidone K30, 0.5 to 5 mass percent of sodium stearate fumarate, 0.5 to 5 mass percent of croscarmellose sodium and 0.3 to 1 mass percent of ferulic acid. The sildenafil orally disintegrating tablet obtained by the invention has the characteristics of simple production process and thorough taste masking.
Description
Technical Field
The invention belongs to the new technical field of medicine manufacturing, and particularly relates to a sildenafil orally disintegrating tablet and a preparation method thereof.
Background
Sildenafil Citrate (Sildenafil Citrate) was a small molecule drug developed by fevered and marketed in the united states in 1998. Can be used for treating pulmonary hypertension, pulmonary hypertension and erectile dysfunction. 26 months 12 and 2019, the national drug administration (NMPA) officially approved Sildenafil picrinate oral disintegrating Tablet (Sildenafil Citrate Orodispersible Tablet) to be marketed. The chemical name of sildenafil citrate is: 1- [ 4-ethoxy-3- (6, 7-dihydro-1-methyl-7-oxo-3-propyl-1 h-pyrazolo [4, 3d ] pyrimidin-5-yl) benzenesulfonyl ] -4-methylpiperazine citrate. The structural formula is as follows:
sildenafil is a selective inhibitor of cyclic guanosine monophosphate (cGMP) specific phosphodiesterase type 5 (PDE 5). The physiological mechanism of penile erection involves the release of Nitric Oxide (NO) from the corpora cavernosa during sexual stimulation. NO activates guanylate cyclase, resulting in increased levels of cyclic guanosine monophosphate (cGMP), which relaxes the smooth muscle in the corpus cavernosum and blood flows in. Sildenafil has NO direct relaxation effect on isolated human cavernous bodies, but can enhance the effect of Nitric Oxide (NO) by inhibiting phosphodiesterase type 5 (PDE 5), which decomposes cGMP in cavernous bodies. When sexual stimulation causes local NO release, sildenafil-inhibiting PDE5 increases the levels of cGMP in the corpus cavernosum, relaxes smooth muscle, and blood flows into the corpus cavernosum. In the absence of sexual stimulation, the recommended dose of sildenafil did not work.
Sildenafil is white or white-like crystal powder, and has no odor and bitter taste. The sildenafil orally disintegrating tablet is mainly used for patients with dysphagia or difficulty and erectile dysfunction patients who are inconvenient to take water to take the medicine, and is directly orally disintegrated and swallowed. The astringent and bitter taste is a key factor influencing the difference of clinical curative effect and the compliance of patients. The prior art solves the technical problem of acedenafil taste astringent and bitter by adopting various methods, but cannot effectively mask the taste.
CN110128429A A sildenafil-acesulfame salt form, its preparation method and application, wherein sildenafil base and acesulfame acid are dissolved or suspended in organic solvent such as ethanol, and sildenafil-acesulfame eutectic is prepared by reaction crystallization to mask taste, but the method has high production cost and can not mask taste for a long time. The sildenafil-acesulfame potassium eutectic salt dissociates in the mouth and the bitter taste of sildenafil begins to be released.
CN104168895A contains sildenafil as active ingredient, high content fast dissolving film for masking bitter taste, and adopts high efficiency taste masking agents of aspartame, sucralose and thaumatin dextrin for taste correction, but the method can not completely mask bitter taste, and excessive sweet taste affects taste.
Therefore, it is urgent to develop a technology capable of effectively masking the taste.
Disclosure of Invention
In view of the defects of the prior art, the invention aims to provide a sildenafil taste masking technology which is simple in production process, low in product cost, thorough in taste masking, safe and effective through a large number of experimental researches.
Compared with the prior art, the sildenafil orally disintegrating tablet has the advantages and remarkable improvements of (1) simple production process; (2) the product cost is low; (3) the taste is completely masked.
The invention is realized by the following technical scheme:
an orally disintegrating tablet of sildenafil, wherein the taste-masking agent is ferulic acid; the sildenafil orally disintegrating tablet comprises 0.3 to 1 mass percent of ferulic acid;
preferably, the sildenafil orally disintegrating tablet comprises 14 to 46 mass percent of sildenafil citrate, 44 to 70 mass percent of mannitol, 5 to 10 mass percent of povidone K30, 0.5 to 5 mass percent of sodium stearate fumarate, 0.5 to 5 mass percent of croscarmellose sodium and 0.3 to 1 mass percent of ferulic acid.
The invention provides a preparation method of sildenafil orally disintegrating tablets, which comprises the following steps:
1) uniformly mixing sildenafil citrate, mannitol and croscarmellose sodium;
2) dissolving povidone K30 with purified water, stirring to clarify, slowly adding into the material obtained in step (1), granulating, and drying to obtain a dried material;
3) adding sodium fumarate stearate into the dried material obtained in the step (2), stirring and sieving to obtain a mixture;
4) adding ferulic acid into the mixture obtained in the step (3), and uniformly mixing to obtain a mixture;
5) the mixture was tabletted using a tabletting machine.
Drawings
FIG. 1 is a graph of bitterness trend measured on an electronic tongue for examples 1, 4, 6, 7, 8 and standard solutions.
Detailed Description
The sildenafil orally disintegrating tablet obtained by the invention has the characteristics of simple production process and thorough taste masking. The following examples illustrate the invention but do not limit it in any way.
Example 1:
prescription:
| sildenafil citrate | 1.400kg |
| Mannitol | 7.020kg |
| Povidone K30 | 1.000kg |
| Croscarmellose sodium | 0.500kg |
| Fumaric acid sodium stearate | 0.050kg |
| Ferulic acid | 0.030kg |
| Making into 10000 tablets |
The preparation method comprises the following steps:
1) uniformly mixing sildenafil citrate, mannitol and croscarmellose sodium;
2) dissolving povidone K30 with purified water, stirring to clarify, slowly adding into the material obtained in step (1), granulating, and drying to obtain a dried material;
3) adding sodium fumarate stearate into the dried material obtained in the step (2), stirring and sieving to obtain a mixture;
4) adding ferulic acid into the mixture obtained in the step (3), and uniformly mixing to obtain a mixture;
5) the mixture was tabletted using a tabletting machine.
Example 2:
prescription:
| sildenafil citrate | 1.400kg |
| Mannitol | 1.305kg |
| Povidone K30 | 0.150kg |
| Croscarmellose sodium | 0.100kg |
| Fumaric acid sodium stearate | 0.030kg |
| Ferulic acid | 0.015kg |
| Making into 10000 tablets |
The preparation method comprises the following steps:
1) uniformly mixing sildenafil citrate, mannitol and croscarmellose sodium;
2) dissolving povidone K30 with purified water, stirring to clarify, slowly adding into the material obtained in step (1), granulating, and drying to obtain a dried material;
3) adding sodium fumarate stearate into the dried material obtained in the step (2), stirring and sieving to obtain a mixture;
4) adding ferulic acid into the mixture obtained in the step (3), and uniformly mixing to obtain a mixture;
5) the mixture was tabletted using a tabletting machine.
Example 3:
prescription:
| sildenafil citrate | 1.400kg |
| Mannitol | 2.165kg |
| Povidone K30 | 0.300kg |
| Croscarmellose sodium | 0.050kg |
| Fumaric acid sodium stearate | 0.060kg |
| Ferulic acid | 0.025kg |
| Making into 10000 tablets |
The preparation method comprises the following steps:
1) uniformly mixing sildenafil citrate, mannitol and croscarmellose sodium;
2) dissolving povidone K30 with purified water, stirring to clarify, slowly adding into the material obtained in step (1), granulating, and drying to obtain a dried material;
3) adding sodium fumarate stearate into the dried material obtained in the step (2), stirring and sieving to obtain a mixture;
4) adding ferulic acid into the mixture obtained in the step (3), and uniformly mixing to obtain a mixture;
5) the mixture was tabletted using a tabletting machine.
Example 4:
prescription:
| sildenafil citrate | 1.400kg |
| Mannitol | 2.865kg |
| Povidone K30 | 0.400kg |
| Croscarmellose sodium | 0.050kg |
| Fumaric acid sodium stearate | 0.250kg |
| Ferulic acid | 0.035kg |
| Making into 10000 tablets |
The preparation method comprises the following steps:
1) uniformly mixing sildenafil citrate, mannitol and croscarmellose sodium;
2) dissolving povidone K30 with purified water, stirring to clarify, slowly adding into the material obtained in step (1), granulating, and drying to obtain a dried material;
3) adding sodium fumarate stearate into the dried material obtained in the step (2), stirring and sieving to obtain a mixture;
4) adding ferulic acid into the mixture obtained in the step (3), and uniformly mixing to obtain a mixture;
5) the mixture was tabletted using a tabletting machine.
Example 5:
prescription:
| sildenafil citrate | 1.400kg |
| Mannitol | 3.900kg |
| Povidone K30 | 0.400kg |
| Croscarmellose sodium | 0.050kg |
| Fumaric acid sodium stearate | 0.200kg |
| Ferulic acid | 0.050kg |
| Making into 10000 tablets |
The preparation method comprises the following steps:
1) uniformly mixing sildenafil citrate, mannitol and croscarmellose sodium;
2) dissolving povidone K30 with purified water, stirring to clarify, slowly adding into the material obtained in step (1), granulating, and drying to obtain a dried material;
3) adding sodium fumarate stearate into the dried material obtained in the step (2), stirring and sieving to obtain a mixture;
4) adding ferulic acid into the mixture obtained in the step (3), and uniformly mixing to obtain a mixture;
5) the mixture was tabletted using a tabletting machine.
Example 6:
prescription:
| sildenafil citrate | 1.400kg |
| Mannitol | 4.800kg |
| Povidone K30 | 0.400kg |
| Croscarmellose sodium | 0.030kg |
| Fumaric acid sodium stearate | 0.300kg |
| Ferulic acid | 0.070kg |
| Making into 10000 tablets |
The preparation method comprises the following steps:
1) uniformly mixing sildenafil citrate, mannitol and croscarmellose sodium;
2) dissolving povidone K30 with purified water, stirring to clarify, slowly adding into the material obtained in step (1), granulating, and drying to obtain a dried material;
3) adding sodium fumarate stearate into the dried material obtained in the step (2), stirring and sieving to obtain a mixture;
4) adding ferulic acid into the mixture obtained in the step (3), and uniformly mixing to obtain a mixture;
5) the mixture was tabletted using a tabletting machine.
Example 7:
prescription:
| sildenafil citrate | 1.400kg |
| Mannitol | 2.890kg |
| Povidone K30 | 0.400kg |
| Croscarmellose sodium | 0.050kg |
| Fumaric acid sodium stearate | 0.250kg |
| Ferulic acid | 0.010kg |
| Making into 10000 tablets |
The preparation method comprises the following steps:
1) uniformly mixing sildenafil citrate, mannitol and croscarmellose sodium;
2) dissolving povidone K30 with purified water, stirring to clarify, slowly adding into the material obtained in step (1), granulating, and drying to obtain a dried material;
3) adding sodium fumarate stearate into the dried material obtained in the step (2), stirring and sieving to obtain a mixture;
4) adding ferulic acid into the mixture obtained in the step (3), and uniformly mixing to obtain a mixture;
5) the mixture was tabletted using a tabletting machine.
Example 8:
prescription:
| sildenafil citrate | 1.400kg |
| Mannitol | 2.890kg |
| Povidone K30 | 0.400kg |
| Croscarmellose sodium | 0.050kg |
| Fumaric acid sodium stearate | 0.250kg |
| Making into 10000 tablets |
The preparation method comprises the following steps:
1) uniformly mixing sildenafil citrate, mannitol and croscarmellose sodium;
2) dissolving povidone K30 with purified water, stirring to clarify, slowly adding into the material obtained in step (1), granulating, and drying to obtain a dried material;
3) adding sodium fumarate stearate into the dried material obtained in the step (2), stirring and sieving to obtain a mixture;
4) adding ferulic acid into the mixture obtained in the step (3), and uniformly mixing to obtain a mixture;
5) the mixture was tabletted using a tabletting machine.
Example 9:
the taste masking effect was measured for sildenafil orally disintegrating tablets produced in example 1, example 4, example 6, example 7 and example 8.
Instruments and equipment: an a-Astree electronic tongue detection device, an SK7200B ultrasonic cleaner; JJl000 electronic balance;
preparing a sample solution:
standard solution: taking a proper amount of sildenafil citrate reference substance, and preparing a solution with the mass fractions of 2%, 4%, 6%, 8%, 10%, 15% and 20%.
Example solutions: taking a proper amount of sildenafil orally disintegrating tablets of example 1, example 4, example 6, example 7 and example 8, and preparing a solution containing sildenafil citrate with the mass fractions of 2%, 4%, 6%, 8%, 10%, 15% and 20%.
And (3) sample determination:
the electronic tongue arrangement (C00 film sensor) used measures the early taste signal value (bitterness) and the aftertaste signal value (aftertaste of bitterness) of the sample solution. The sensor needs to be activated before use. 200 of this internal solution (3.33mol/L KCl +0.07 mmol/L AgCI) was added to the sensor interior and activated for at least 24h by immersion in a reference solution (0.3mmol/L tartaric acid +30mmol/L KCl). The activated sensors were in standard and example solutions. The results are shown in Table 1
Table 1 example 1, example 4, example 6, example 7, example 8 and standard solution electronic tongue measurement bitterness value
| 2% | 4% | 6% | 8% | 10% | 15% | 20% | |
| Standard solution | 7.93 | 9.17 | 10.54 | 11.74 | 12.19 | 13.24 | 14.21 |
| Example 1 | -0.34 | 0.01 | -0.02 | -0.37 | 0.11 | 0.14 | 0.21 |
| Example 4 | -0.13 | -0.15 | -0.11 | 0.01 | -0.36 | -0.11 | -0.43 |
| Example 6 | -0.11 | -0.21 | -0.17 | -0.32 | -0.15 | -0.11 | -0.03 |
| Example 7 | 0.04 | 0.09 | 1.49 | 6.85 | 10.97 | 12.11 | 13.98 |
| Example 8 | 7.65 | 8.96 | 10.7 | 12.01 | 12.35 | 13.01 | 14.79 |
Claims (3)
1. An orally disintegrating tablet of sildenafil characterized in that: the sildenafil orally disintegrating tablet taste masking agent is ferulic acid; the sildenafil orally disintegrating tablet comprises 0.3 to 1 mass percent of ferulic acid.
2. The sildenafil orally disintegrating tablet according to claim 1, wherein: comprises 14 to 46 percent of sildenafil citrate, 44 to 70 percent of mannitol, 5 to 10 percent of povidone K30, 0.5 to 5 percent of sodium fumarate stearate, 0.5 to 5 percent of croscarmellose sodium and 0.3 to 1 percent of ferulic acid.
3. A preparation method of sildenafil orally disintegrating tablets is characterized by comprising the following steps:
1) uniformly mixing sildenafil, mannitol and croscarmellose sodium;
2) dissolving povidone K30 with purified water, stirring to clarify, slowly adding into the material obtained in step (1), granulating, and drying to obtain a dried material;
3) adding sodium fumarate stearate into the dried material obtained in the step (2), stirring and sieving to obtain a mixture;
4) adding ferulic acid into the mixture obtained in the step (3), and uniformly mixing to obtain a mixture;
5) the mixture was tabletted using a tabletting machine.
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| CN101460150A (en) * | 2006-03-31 | 2009-06-17 | 鲁比康研究私人有限公司 | Directly compressible composite for orally disintegrating tablets |
| CN101579320A (en) * | 2008-05-12 | 2009-11-18 | 张正生 | Sildenafil citrate sublingual tablet and preparation method thereof |
| CN101683324A (en) * | 2008-09-27 | 2010-03-31 | 张晓芳 | Oral disintegrative tablet of sildenafil citrate and preparation method thereof |
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