CN114712322A - Tablet of ebastine salt and preparation method thereof - Google Patents
Tablet of ebastine salt and preparation method thereof Download PDFInfo
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- CN114712322A CN114712322A CN202210355186.7A CN202210355186A CN114712322A CN 114712322 A CN114712322 A CN 114712322A CN 202210355186 A CN202210355186 A CN 202210355186A CN 114712322 A CN114712322 A CN 114712322A
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- ebastine
- salt
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- granules
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- MJJALKDDGIKVBE-UHFFFAOYSA-N ebastine Chemical class C1=CC(C(C)(C)C)=CC=C1C(=O)CCCN1CCC(OC(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 MJJALKDDGIKVBE-UHFFFAOYSA-N 0.000 title claims abstract description 67
- 238000002360 preparation method Methods 0.000 title claims abstract description 16
- 229960001971 ebastine Drugs 0.000 claims abstract description 46
- 239000008187 granular material Substances 0.000 claims abstract description 45
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims abstract description 26
- 239000011248 coating agent Substances 0.000 claims abstract description 22
- 238000000576 coating method Methods 0.000 claims abstract description 22
- 150000003839 salts Chemical class 0.000 claims abstract description 18
- 238000000034 method Methods 0.000 claims abstract description 16
- 229920002785 Croscarmellose sodium Polymers 0.000 claims abstract description 13
- 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 abstract description 13
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims abstract description 13
- 229920002472 Starch Polymers 0.000 claims abstract description 13
- 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 13
- 229960001681 croscarmellose sodium Drugs 0.000 claims abstract description 13
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims abstract description 13
- 239000008101 lactose Substances 0.000 claims abstract description 13
- 235000019359 magnesium stearate Nutrition 0.000 claims abstract description 13
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims abstract description 13
- 239000008108 microcrystalline cellulose Substances 0.000 claims abstract description 13
- 229940016286 microcrystalline cellulose Drugs 0.000 claims abstract description 13
- 235000019698 starch Nutrition 0.000 claims abstract description 13
- 239000008107 starch Substances 0.000 claims abstract description 13
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims abstract description 11
- 238000001035 drying Methods 0.000 claims abstract description 9
- 239000000203 mixture Substances 0.000 claims abstract description 5
- 238000002156 mixing Methods 0.000 claims abstract description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 18
- 239000008213 purified water Substances 0.000 claims description 13
- 238000012360 testing method Methods 0.000 claims description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 claims description 6
- 239000007888 film coating Substances 0.000 claims description 6
- 238000009501 film coating Methods 0.000 claims description 6
- 239000000080 wetting agent Substances 0.000 claims description 6
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 4
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 claims description 4
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 4
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 3
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 3
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 3
- 229940093429 polyethylene glycol 6000 Drugs 0.000 claims description 3
- 239000004408 titanium dioxide Substances 0.000 claims description 3
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 229940077388 benzenesulfonate Drugs 0.000 claims 1
- 150000004701 malic acid derivatives Chemical class 0.000 claims 1
- 238000010998 test method Methods 0.000 claims 1
- 229940079593 drug Drugs 0.000 abstract description 4
- 239000003814 drug Substances 0.000 abstract description 4
- 150000007524 organic acids Chemical class 0.000 abstract description 2
- 239000003826 tablet Substances 0.000 description 74
- 238000001514 detection method Methods 0.000 description 22
- 238000007689 inspection Methods 0.000 description 11
- 229960001375 lactose Drugs 0.000 description 9
- 229940032147 starch Drugs 0.000 description 9
- 238000005520 cutting process Methods 0.000 description 6
- 239000002245 particle Substances 0.000 description 6
- 239000004033 plastic Substances 0.000 description 6
- 229920003023 plastic Polymers 0.000 description 6
- 239000007779 soft material Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 239000007916 tablet composition Substances 0.000 description 6
- 238000005303 weighing Methods 0.000 description 6
- 238000004090 dissolution Methods 0.000 description 5
- 238000007922 dissolution test Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 229940049920 malate Drugs 0.000 description 3
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 3
- 238000009472 formulation Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 201000004624 Dermatitis Diseases 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 206010039085 Rhinitis allergic Diseases 0.000 description 1
- 208000036284 Rhinitis seasonal Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 201000010105 allergic rhinitis Diseases 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 208000030949 chronic idiopathic urticaria Diseases 0.000 description 1
- 206010072757 chronic spontaneous urticaria Diseases 0.000 description 1
- 208000024376 chronic urticaria Diseases 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- -1 ebastine salts Chemical class 0.000 description 1
- 239000002662 enteric coated tablet Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000938 histamine H1 antagonist Substances 0.000 description 1
- 125000001165 hydrophobic group Chemical group 0.000 description 1
- 229960003943 hypromellose Drugs 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000003973 paint Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000012797 qualification Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000001932 seasonal effect Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229960005196 titanium dioxide Drugs 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
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
- A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
-
- 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
- A61P11/02—Nasal agents, e.g. decongestants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/04—Antipruritics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Dermatology (AREA)
- Epidemiology (AREA)
- Pulmonology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Immunology (AREA)
- Otolaryngology (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention provides a preparation method of an ebastine salt tablet, which comprises the following steps: s1, putting ebastine salt, lactose, starch and microcrystalline cellulose in a wet granulating machine to complete the granulating process, and drying to obtain dry granules; s2, mixing the dry granules obtained in the step S1 with magnesium stearate and croscarmellose sodium to prepare intermediate granules, and tabletting the intermediate granules to prepare intermediate plain tablets; s3, coating the intermediate tablet obtained in S2 to obtain an intermediate coated tablet, namely the ebastine salt tablet; in S1, the composition comprises, by mass, 5-10 parts of ebastine salt, 65-70 parts of lactose, 3-8 parts of microcrystalline cellulose and 10-20 parts of starch; in S2, the coating comprises, by mass, 1-3 parts of croscarmellose sodium and 0.5-2.0 parts of magnesium stearate. The invention improves the solubility of the drug by using the water-soluble salt generated by the ebastine and the organic acid.
Description
Technical Field
The invention relates to an ebastine salt tablet and a preparation method thereof.
Background
Ebastine (Ebastine, chemical name is 1- [4- (1, 1-dimethyl ethyl) phenyl ] -4- [4- (diphenyl methoxy) -1-piperidyl ] -1-butanone) is a long-acting, strong and high-selectivity histamine H1 receptor blocker, and is clinically used for treating allergic diseases, including seasonal and allergic rhinitis, chronic idiopathic urticaria, eczema, skin pruritus and other diseases.
Because the molecular structure of ebastine contains a plurality of hydrophobic groups, the ebastine is insoluble in water, the dissolution rate of the tablet in vitro is slow, the bioavailability is low, the tablet is difficult to absorb in vivo, and the treatment effect of ebastine is limited.
Disclosure of Invention
The invention aims to overcome the defects in the prior art, and provides an ebastine salt tablet and a preparation method thereof.
In order to solve the technical problems, the invention adopts the technical scheme that: a process for the preparation of tablets of a salt of ebastine comprising the steps of:
s1, putting ebastine salt, lactose, starch and microcrystalline cellulose in a wet granulating machine to complete the granulating process, and drying to obtain dry granules;
s2, mixing the dry granules obtained in the S1 with magnesium stearate and croscarmellose sodium to prepare intermediate granules, and tabletting the intermediate granules to prepare intermediate plain tablets;
s3, coating the intermediate tablet obtained in S2 to obtain an intermediate coated tablet, namely the ebastine salt tablet;
in S1, the composition comprises, by mass, 5-10 parts of ebastine salt, 65-70 parts of lactose, 3-8 parts of microcrystalline cellulose and 10-20 parts of starch;
in S2, the coating comprises, by mass, 1-3 parts of croscarmellose sodium and 0.5-2.0 parts of magnesium stearate.
Further, the salt of ebastine includes hydrochloride, sulfate, besylate, maleate, and malate of ebastine. .
Further, after obtaining the intermediate particles and obtaining the intermediate plain film in S2, carrying out inspection, wherein the inspection process comprises intermediate particle inspection and intermediate plain film inspection, the angle of repose of the intermediate particles is not more than 40 degrees, and the tap density is 0.40-0.90 g/ml; the hardness of the intermediate plain tablets is in the range of 3-6 kg.
Further, the water-based paint also comprises a wetting agent, wherein the wetting agent is purified water and accounts for 50-70 parts by mass.
Further, the coating comprises 1-4 parts of film coating premix and 10-40 parts of purified water in parts by mass; the film coating premix comprises titanium dioxide, hydroxypropyl methylcellulose and polyethylene glycol 6000.
A tablet of a salt of ebastine prepared according to the process for preparing the tablet of a salt of ebastine.
Compared with the prior art, the invention has the beneficial effects that: the water-soluble salt is generated by the ebastine and the organic acid, so that the solubility of the drug is improved, the water solubility of the ebastine is improved, the dissolution of the tablet outside a human body is accelerated, the bioavailability of the tablet is improved, and the curative effect of the drug is fully exerted.
Detailed Description
It is easily understood that according to the technical solution of the present invention, a person skilled in the art can propose various alternative structures and implementation ways without changing the spirit of the present invention. Therefore, the following detailed description is merely illustrative of the technical aspects of the present invention, and should not be construed as limiting or restricting the technical aspects of the present invention.
The tablet of the ebastine salt is mainly prepared from the following raw and auxiliary materials: the enteric-coated tablet comprises, by mass, 5-10 parts of ebastine salt (calculated by ebastine), 65-70 parts of lactose, 3-8 parts of microcrystalline cellulose and 10-20 parts of starch as fillers, 50-70 parts of purified water as a granulating wetting agent, 1-3 parts of croscarmellose sodium as a disintegrating agent, 0.5-2 parts of magnesium stearate as a lubricant, 1-4 parts of a film coating premix as a coating material and 10-40 parts of purified water as a coating solvent.
A typical formulation of the present invention is shown in table 1 below:
TABLE 1 Ebastine tablet formulation
The film coating premix comprises titanium dioxide, hypromellose, and polyethylene glycol 6000
The preparation method of the tablet of the ebastine salt is as follows:
weighing salt of ebastine, lactose, starch and microcrystalline cellulose, adding into a wet granulator, stirring, cutting, adding purified water to obtain soft material, wet granulating with a granulator, and drying with a fluidized bed. The dry granules were mixed with magnesium stearate and croscarmellose sodium to make intermediate granules. And (4) taking the intermediate granules for detection, and tabletting the intermediate granules after the intermediate granules are qualified to prepare the intermediate plain tablets. And (5) taking the intermediate plain tablets for detection, and coating the intermediate plain tablets after the intermediate plain tablets are qualified through inspection to obtain the intermediate coated tablets. And (4) taking the intermediate coated tablet for detection, and carrying out aluminum-plastic and outer coating on the intermediate coated tablet after the intermediate coated tablet is inspected to be qualified.
The testing process comprises an intermediate particle testing and an intermediate plain film testing,
the intermediate particle test items include:
angle of repose
The detection method comprises the following steps: using an angle of repose tester, detecting the angle of repose of the particles according to an operation rule for 3 times, and taking an average value of the 3 times of data; the qualified standard is as follows: the angle of repose theta is less than or equal to 40 degrees.
(ii) bulk and tap Density
The detection method comprises the following steps: according to 0993 bulk density and tap density determination method of the general rule of the four departments in the Chinese pharmacopoeia, the first standard of qualification of normal strength and gas is as follows: the tap density is 0.40-0.90 g/ml.
The intermediate prime test items comprise:
hardness (1)
The detection method comprises the following steps: detecting the hardness of the tablets by using a tablet hardness tester according to the operation rules, and detecting 20 tablets; the qualified standard is that the hardness of the plain sheet is within the range of 3-6 kg.
Hardness of brittleness-
The detection method comprises the following steps: according to 0923 tablet friability inspection method of the four ministry of general rules of China pharmacopoeia; the qualified standard is specified in Chinese pharmacopoeia.
The technical effects of the present invention will be further described with reference to the following examples.
Determination of saturation solubility of ebastine and salts thereof
Adding excessive ebastine and ebastine salt into a test tube with plug containing 50ml of purified water, placing in a constant temperature shaking table, shaking at 25 deg.C for 24 hr, centrifuging supernatant, and measuring the concentration of ebastine and ebastine salt. And (3) continuing shaking the constant-temperature shaking table with the plug test tube for 48 hours, taking the supernatant again for centrifugation, measuring the concentration of the ebastine and the salt of the ebastine, and if the detection result of the concentration of the drug corresponding to the two tests is not changed greatly, determining the result as the saturated solubility. The solubility in saline of ebastine was significantly improved as shown by the results of the solubility measurement, and the results of the saturation solubility measurement are shown in Table 2.
TABLE 2 solubility in Water (mg/ml) of ebastine and pharmaceutical salts of ebastine
Example 1
TABLE 3 Ebastine hydrochloride tablet formulation
The preparation method comprises the following steps:
weighing ebastine hydrochloride, lactose, starch and microcrystalline cellulose, putting into a wet granulator, stirring, cutting, adding purified water to prepare soft material, wet granulating by a granulator, and drying by a fluidized bed. The dry granules were mixed with magnesium stearate and croscarmellose sodium to make intermediate granules. And (4) taking the intermediate granules for detection, and tabletting the intermediate granules after the intermediate granules are qualified to prepare the intermediate plain tablets. And (5) taking the intermediate plain tablets for detection, and coating the intermediate plain tablets after the intermediate plain tablets are qualified through inspection to obtain the intermediate coated tablets. And (4) taking the intermediate coated tablet for detection, and carrying out aluminum-plastic and outer coating on the intermediate coated tablet after the intermediate coated tablet is inspected to be qualified.
Example 2
TABLE 4 Ebastine sulfate tablet formulation
The preparation method comprises the following steps:
weighing ebastine sulfate, lactose, starch and microcrystalline cellulose, putting into a wet granulator, stirring, cutting, adding purified water to prepare soft material, wet granulating by a granulator, and drying by a fluidized bed. Mixing the dry granules with magnesium stearate and croscarmellose sodium to obtain intermediate granules. And (4) taking the intermediate granules for detection, and tabletting the intermediate granules after the intermediate granules are qualified to prepare the intermediate plain tablets. And (5) taking the intermediate plain tablets for detection, and coating the intermediate plain tablets after the intermediate plain tablets are qualified through inspection to obtain the intermediate coated tablets. And (4) taking the intermediate coated tablet for detection, and carrying out aluminum-plastic and outer coating on the intermediate coated tablet after the intermediate coated tablet is inspected to be qualified.
Example 3
TABLE 5 Ebastine besylate tablet formulation
The preparation method comprises the following steps:
weighing ebastine besylate, lactose, starch and microcrystalline cellulose into a wet granulator, stirring, cutting, adding purified water to prepare soft materials, wet granulating by a granulator, and drying by a fluidized bed. The dry granules were mixed with magnesium stearate and croscarmellose sodium to make intermediate granules. And (4) taking the intermediate granules for detection, and tabletting the intermediate granules after the intermediate granules are qualified to prepare the intermediate plain tablets. And (5) taking the intermediate plain tablets for detection, and coating the intermediate plain tablets after the intermediate plain tablets are qualified through inspection to obtain the intermediate coated tablets. And (4) taking the intermediate coated tablet for detection, and carrying out aluminum-plastic and outer coating on the intermediate coated tablet after the intermediate coated tablet is inspected to be qualified.
Example 4
TABLE 6 Ebastin malate tablet formulation
The preparation method comprises the following steps:
weighing ebastine malate, lactose, starch and microcrystalline cellulose, putting into a wet granulator, stirring, cutting, adding purified water to prepare soft material, wet granulating by a granulator, and drying by a fluidized bed. The dry granules were mixed with magnesium stearate and croscarmellose sodium to make intermediate granules. And (4) taking the intermediate granules for detection, and tabletting the intermediate granules after the intermediate granules are qualified to prepare the intermediate plain tablets. And (5) taking the intermediate plain tablets for detection, and coating the intermediate plain tablets after the intermediate plain tablets are qualified through inspection to obtain the intermediate coated tablets. And (4) taking the intermediate coated tablet for detection, and carrying out aluminum-plastic and outer coating on the intermediate coated tablet after the intermediate coated tablet is inspected to be qualified.
Example 5
TABLE 7 Ebastine maleate tablet formulation
The preparation method comprises the following steps:
weighing ebastine maleate, lactose, starch and microcrystalline cellulose, putting into a wet granulator, stirring, cutting, adding purified water to make soft material, wet granulating by a granulator, and drying with a fluidized bed. The dry granules were mixed with magnesium stearate and croscarmellose sodium to make intermediate granules. And (4) taking the intermediate granules for detection, and tabletting the intermediate granules after the intermediate granules are qualified to prepare the intermediate plain tablets. And (4) detecting the intermediate plain tablets, and coating the intermediate plain tablets after the intermediate plain tablets are qualified through inspection to obtain intermediate coated tablets. And (4) taking the intermediate coated tablet for detection, and carrying out aluminum-plastic and outer coating on the intermediate coated tablet after the intermediate coated tablet is inspected to be qualified.
Tablet dissolution test analysis of ebastine salts
Referring to the determination method of dissolution rate and release rate of Chinese pharmacopoeia 0931, combining the characteristics of the product, taking tablets of Ebastine salt and commercially available preparations (Ebastine, Ebastine tablets) in the above examples to perform dissolution test, and the test conditions are as follows: medium: ph1.2(7.65ml hydrochloric acid to 1000ml water), second method (paddle method), temperature: 37.0 +/-0.5 ℃ and 75 revolutions per minute. Samples were taken at 5min, 10min, 15min, 20min, 30min, 45min and 60min, respectively, and the dissolution of the ebastine salt tablets and the commercially available formulations was examined, and the results are shown in table 8.
TABLE 8 dissolution test results of examples 1 to 5
From the above test results, it is found that the tablet of the ebastine pharmaceutical salt has a faster dissolution rate in a medium of pH1.2 than the commercially available preparation.
The technical scope of the present invention is not limited to the above description, and those skilled in the art can make various changes and modifications to the above-described embodiments without departing from the technical spirit of the present invention, and such changes and modifications should fall within the protective scope of the present invention.
Claims (6)
1. A process for the preparation of tablets of a salt of ebastine comprising the steps of:
s1, putting ebastine salt, lactose, starch and microcrystalline cellulose into a wet granulating machine to complete the granulating process, and drying to obtain dry granules;
s2, mixing the dry granules obtained in the step S1 with magnesium stearate and croscarmellose sodium to prepare intermediate granules, and tabletting the intermediate granules to prepare intermediate plain tablets;
s3, coating the intermediate tablet obtained in S2 to obtain an intermediate coated tablet, namely the ebastine salt tablet;
in S1, the composition comprises, by mass, 5-10 parts of ebastine salt, 65-70 parts of lactose, 3-8 parts of microcrystalline cellulose and 10-20 parts of starch;
in S2, the coating comprises, by mass, 1-3 parts of croscarmellose sodium and 0.5-2.0 parts of magnesium stearate.
2. The method for preparing a tablet of a salt of ebastine as claimed in claim 1, wherein the salt of ebastine comprises hydrochloride, sulfate, benzenesulfonate, maleate, or malate salt of ebastine.
3. The method of claim 1, wherein the intermediate granules obtained in step S2 and the intermediate tablets obtained in step S are tested, wherein the test procedure comprises intermediate granule test and intermediate tablet test, the intermediate granules have an angle of repose of not more than 40 ° and a tap density of 0.40-0.90 g/ml; the hardness of the intermediate plain tablets is in the range of 3-6 kg.
4. The method for preparing a tablet of a salt of ebastine as claimed in claim 1, further comprising a wetting agent, wherein the wetting agent is purified water, and the mass part of the wetting agent is 50-70 parts.
5. The process for preparing a tablet of a salt of ebastine as claimed in claim 1, wherein the coating comprises 1-4 parts by mass of a film coating premix and 10-40 parts by mass of purified water; the film coating premix comprises titanium dioxide, hydroxypropyl methylcellulose and polyethylene glycol 6000.
6. A tablet of a salt of ebastine, prepared according to the process for the preparation of a tablet of a salt of ebastine as claimed in any one of claims 1 to 5.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210355186.7A CN114712322A (en) | 2022-04-01 | 2022-04-01 | Tablet of ebastine salt and preparation method thereof |
Applications Claiming Priority (1)
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Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070059371A1 (en) * | 2005-06-09 | 2007-03-15 | Elan Pharma International, Limited | Nanoparticulate ebastine formulations |
| CN101161233A (en) * | 2007-11-29 | 2008-04-16 | 湖北丽益医药科技有限公司 | Ebstine solid oral preparation and its preparing method |
| US20090304791A1 (en) * | 2005-11-04 | 2009-12-10 | Simbec Iberica, S.L. | Solid oral forms of ebastine |
| JP2012031164A (en) * | 2010-07-06 | 2012-02-16 | Teika Seiyaku Kk | Film-shaped preparation |
| WO2012076919A1 (en) * | 2010-12-11 | 2012-06-14 | Micro Labs Limited | Process of preparing ebastine |
| WO2013081562A1 (en) * | 2011-10-13 | 2013-06-06 | Mahmut Bilgic | Oral formulations comprising ebastine |
| CN114014796A (en) * | 2021-11-16 | 2022-02-08 | 江苏联环药业股份有限公司 | Epstein salt and preparation method and application thereof |
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2022
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Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070059371A1 (en) * | 2005-06-09 | 2007-03-15 | Elan Pharma International, Limited | Nanoparticulate ebastine formulations |
| US20090304791A1 (en) * | 2005-11-04 | 2009-12-10 | Simbec Iberica, S.L. | Solid oral forms of ebastine |
| CN101161233A (en) * | 2007-11-29 | 2008-04-16 | 湖北丽益医药科技有限公司 | Ebstine solid oral preparation and its preparing method |
| JP2012031164A (en) * | 2010-07-06 | 2012-02-16 | Teika Seiyaku Kk | Film-shaped preparation |
| WO2012076919A1 (en) * | 2010-12-11 | 2012-06-14 | Micro Labs Limited | Process of preparing ebastine |
| WO2013081562A1 (en) * | 2011-10-13 | 2013-06-06 | Mahmut Bilgic | Oral formulations comprising ebastine |
| CN114014796A (en) * | 2021-11-16 | 2022-02-08 | 江苏联环药业股份有限公司 | Epstein salt and preparation method and application thereof |
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