CN114983956A - Mirabegron sustained release tablet and preparation method thereof - Google Patents
Mirabegron sustained release tablet and preparation method thereof Download PDFInfo
- Publication number
- CN114983956A CN114983956A CN202210549286.3A CN202210549286A CN114983956A CN 114983956 A CN114983956 A CN 114983956A CN 202210549286 A CN202210549286 A CN 202210549286A CN 114983956 A CN114983956 A CN 114983956A
- Authority
- CN
- China
- Prior art keywords
- mirabegron
- release tablet
- sustained
- mirabegron sustained
- sustained release
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- PBAPPPCECJKMCM-IBGZPJMESA-N mirabegron Chemical compound S1C(N)=NC(CC(=O)NC=2C=CC(CCNC[C@H](O)C=3C=CC=CC=3)=CC=2)=C1 PBAPPPCECJKMCM-IBGZPJMESA-N 0.000 title claims abstract description 61
- 229960001551 mirabegron Drugs 0.000 title claims abstract description 59
- 239000007939 sustained release tablet Substances 0.000 title claims abstract description 41
- 238000002360 preparation method Methods 0.000 title claims abstract description 14
- 239000011248 coating agent Substances 0.000 claims abstract description 17
- 238000000576 coating method Methods 0.000 claims abstract description 17
- 239000002202 Polyethylene glycol Substances 0.000 claims abstract description 15
- 229920001223 polyethylene glycol Polymers 0.000 claims abstract description 15
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims abstract description 12
- 235000021355 Stearic acid Nutrition 0.000 claims abstract description 11
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims abstract description 11
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims abstract description 11
- 239000008117 stearic acid Substances 0.000 claims abstract description 11
- 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 claims abstract description 9
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims abstract description 9
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims abstract description 9
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims abstract description 9
- 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 abstract description 9
- 239000000661 sodium alginate Substances 0.000 claims abstract description 9
- 235000010413 sodium alginate Nutrition 0.000 claims abstract description 9
- 229940005550 sodium alginate Drugs 0.000 claims abstract description 9
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims abstract description 8
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims abstract description 8
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims abstract description 8
- 235000019359 magnesium stearate Nutrition 0.000 claims abstract description 6
- 239000008187 granular material Substances 0.000 claims description 12
- 239000003826 tablet Substances 0.000 claims description 11
- 238000002156 mixing Methods 0.000 claims description 10
- 238000007873 sieving Methods 0.000 claims description 10
- 239000011230 binding agent Substances 0.000 claims description 8
- 238000005507 spraying Methods 0.000 claims description 8
- 239000000725 suspension Substances 0.000 claims description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 8
- 238000005303 weighing Methods 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 6
- 239000007888 film coating Substances 0.000 claims description 4
- 238000009501 film coating Methods 0.000 claims description 4
- 238000003825 pressing Methods 0.000 claims description 4
- 239000008213 purified water Substances 0.000 claims description 4
- 238000005469 granulation Methods 0.000 claims description 3
- 230000003179 granulation Effects 0.000 claims description 3
- 239000002245 particle Substances 0.000 claims description 3
- 238000009776 industrial production Methods 0.000 abstract description 2
- 230000000052 comparative effect Effects 0.000 description 10
- 239000000203 mixture Substances 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- 239000000463 material Substances 0.000 description 8
- 239000003814 drug Substances 0.000 description 7
- 238000009472 formulation Methods 0.000 description 5
- 206010020853 Hypertonic bladder Diseases 0.000 description 4
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 4
- 208000009722 Overactive Urinary Bladder Diseases 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 208000020629 overactive bladder Diseases 0.000 description 4
- -1 2-aminothiazole-4-yl Chemical group 0.000 description 3
- 239000003963 antioxidant agent Substances 0.000 description 3
- 230000003078 antioxidant effect Effects 0.000 description 3
- 238000004090 dissolution Methods 0.000 description 3
- 238000007922 dissolution test Methods 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000012535 impurity Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 239000000048 adrenergic agonist Substances 0.000 description 2
- 230000001186 cumulative effect Effects 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 229910052742 iron Inorganic materials 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 229940120393 myrbetriq Drugs 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- SPSPIUSUWPLVKD-UHFFFAOYSA-N 2,3-dibutyl-6-methylphenol Chemical compound CCCCC1=CC=C(C)C(O)=C1CCCC SPSPIUSUWPLVKD-UHFFFAOYSA-N 0.000 description 1
- 102000012367 Beta 3 adrenoceptor Human genes 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000004353 Polyethylene glycol 8000 Substances 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 229940051881 anilide analgesics and antipyretics Drugs 0.000 description 1
- 102000015005 beta-adrenergic receptor activity proteins Human genes 0.000 description 1
- 108040006818 beta-adrenergic receptor activity proteins Proteins 0.000 description 1
- 108040005346 beta3-adrenergic receptor activity proteins Proteins 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 230000007797 corrosion Effects 0.000 description 1
- 238000005260 corrosion Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000012738 dissolution medium Substances 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- YOBAEOGBNPPUQV-UHFFFAOYSA-N iron;trihydrate Chemical compound O.O.O.[Fe].[Fe] YOBAEOGBNPPUQV-UHFFFAOYSA-N 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000008055 phosphate buffer solution Substances 0.000 description 1
- 229940085678 polyethylene glycol 8000 Drugs 0.000 description 1
- 235000019446 polyethylene glycol 8000 Nutrition 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
Images
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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/426—1,3-Thiazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
- A61K9/2813—Inorganic compounds
-
- 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
- A61K9/2853—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers, poly(lactide-co-glycolide)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/10—Drugs for disorders of the urinary system of the bladder
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Inorganic Chemistry (AREA)
- Urology & Nephrology (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 discloses a mirabegron sustained release tablet and a preparation method thereof. The mirabegron sustained release tablet comprises the following components in percentage by weight: 0.5-25% of mirabegron, 1-40% of hydroxypropyl methylcellulose, 1-40% of sodium alginate, 10-60% of polyethylene glycol, 0.5-30% of stearic acid, 0.1-20% of hydroxypropyl cellulose, 0.01-5% of magnesium stearate and 0.5-20% of coating premix. The mirabegron sustained release tablet provided by the invention has the advantages of long release time, high safety, complete release, improved bioavailability, simple preparation and suitability for industrial production.
Description
Technical Field
The invention belongs to the field of pharmaceutical preparations, and mainly relates to a mirabegron sustained-release tablet and a preparation method thereof.
Background
The chemical name of the mirabegron is R) -2- (2-aminothiazole-4-yl) -4' - [2- [ (2-hydroxy-2-phenylethyl) amino]Ethyl radical]Acetic acid anilides of formula C 21 H 24 N 4 O 2 S, the structural formula is as follows:
mirabegron is an arolamine beta-3 adrenergic agonist developed by anstela pharmaceuticals in japan, and tablets are marketed in japan at 2011 in 9/16 and 2012 in 6/28 under the trade name Myrbetriq for use in the treatment of overactive bladder (OAB) by the united states food and drug administration. Mirabegron is the first beta 3 adrenoceptor agonist drug used to treat overactive bladder, and its successful marketing fills the gap in the treatment of overactive bladder with beta adrenoceptor agonists. The mirabegron mainly acts on a beta 3 receptor to relax the detrusor muscle of the bladder and increase the stability of the detrusor muscle, and in vivo studies show that the mirabegron can inhibit average bladder pressure and micro-contraction quantity after being administrated, and effectively promote bladder storage.
In order to maximize the pharmacological effects of the control bladder, the development of a formulation of mirabegron for modulating the release, prolonging the duration of action of the drug, is required. The distribution and metabolism of the mirabegron in the body are easily influenced by food, so that a sustained-release preparation is required to slowly release the medicine at a non-constant speed according to requirements, the administration frequency is relatively reduced, the curative effect or compliance of a patient is obviously improved, and the clinical curative effect is improved.
Patent application CN105232448A discloses a mirabegron controlled release pharmaceutical composition, which can improve the decrease of blood concentration caused by food, and selects polyoxyethylene as a slow release retardant, a large amount of ether bonds exist on a branch chain, and the ether bonds are easily affected by the outside so as to be oxidized and degraded, so that dibutyl hydroxy toluene is added as an antioxidant, and the distribution degree of the antioxidant can influence the tabletting and tablet release effects. The patent CN104523635B selects hydroxypropyl methyl cellulose as a framework material, the tablet can be released for 8 hours after being taken orally, the antioxidant is not suitable, the drug effect and the safety are ensured, but the tabletting process is more complex and has high requirements.
Therefore, the sustained release tablets of mirabegron, which can be sustained and released at a non-constant speed for a long time, are completely released and have a simple preparation process, are urgently needed to be developed.
Disclosure of Invention
The invention aims to overcome the defects in the prior art and provides a mirabegron sustained release tablet and a preparation method thereof.
The invention provides a mirabegron sustained release tablet, which is composed of mirabegron as an active ingredient and pharmaceutic adjuvants.
Specifically, the mirabegron sustained release tablet comprises the following components in parts by weight:
the number average molecular weight of the polyethylene glycol is 5000-10000, wherein the polyethylene glycol belongs to a high molecular polymer, the high molecular polymer is composed of homologous mixtures with the same chemical composition and different polymerization degrees, and the average molecular weight is generally adopted to characterize the size of molecules and is called as the number average molecular weight.
The weight ratio of the hydroxypropyl cellulose to the sodium alginate is preferably 1 (0.2-5), and more preferably 1 (0.5-2).
The weight ratio of the polyethylene glycol to the stearic acid is preferably 10 (1-7), and more preferably 10: (2-5).
The coating premix is a stomach-soluble coating premix which is commercially available and comprises 69.653% of hydroxypropyl methylcellulose, 13.024% of polyethylene glycol 8000, 14.44% of iron dye yellow oxide and 3% of iron dye red oxide.
Preferably, the mirabegron sustained release tablet comprises the following components in parts by weight:
in a preferred technical scheme, the mirabegron sustained release tablet comprises the following components in parts by weight:
in another aspect of the invention, a preparation method of the mirabegron sustained release tablet is provided, which specifically comprises the following steps:
1, pretreatment: weighing polyethylene glycol and stearic acid according to the prescription amount, crushing and sieving, weighing hydroxypropyl methylcellulose, sodium alginate and mirabegron according to the prescription amount, mixing and sieving.
2, fluidized bed one-step granulation: dissolving a prescribed amount of hydroxypropyl cellulose in a proper amount of water to prepare a binder solution, adding the premix obtained in the step (1) into a fluidized bed, and spraying the binder solution to granulate in one step.
3, total mixing: and (3) adding the granules prepared in the step (2) into magnesium stearate and uniformly mixing.
4, tabletting: and (4) pressing the total mixed particles obtained in the step (3) into tablets.
5, coating: and (3) dissolving the stomach-soluble film coating premix with the prescription amount in purified water to prepare uniform suspension, transferring the plain tablets obtained in the step (4) into a coating pot, and spraying the coating suspension to obtain the mirabegron sustained-release tablets.
The invention has the advantages of
Compared with the mirabegron sustained release tablet and the preparation method thereof disclosed by the prior art, the mirabegron sustained release tablet and the preparation method thereof provided by the invention have the advantages that the hydroxypropyl methylcellulose and the sodium alginate are selected as hydrophilic gel framework materials, so that the release duration and the cumulative release amount of active ingredients of the mirabegron can be optimal, in addition, the corrosion sustained release framework materials in the invention are selected from the polyethylene glycol and the stearic acid, and the particle size of the auxiliary materials is controlled, so that the auxiliary materials are not easy to separate in the fluidized bed granulation process, therefore, a direct pressure method can be selected for tabletting, the preparation process is simpler and more convenient and easier to operate, and the mirabegron sustained release tablet is more suitable for industrial production. The mirabegron sustained release tablet obtained by the technical scheme of the invention can be released for 12 hours after being orally taken, and the release amount is more than 90 percent, so that the bioavailability is high.
Drawings
FIG. 1: dissolution curve investigation chart of mirabegron sustained release tablets prepared in examples 1-6 and comparative examples 1-2 and purchased original products (using phosphoric acid solution with pH6.8 as dissolution medium)
Detailed Description
For better understanding of the technical solutions of the present invention, the technical solutions of the present invention are further described below with reference to specific examples, which are only for assisting understanding of the present invention and should not be construed as specifically limiting the present invention.
In this embodiment, the mirabegron raw material, the auxiliary material and the coating premix are all commercially available.
Examples 1-6 formulations of mirabegron sustained release tablets are shown in the following table (unit: g):
| composition of matter | Example 1 | Example 2 | Example 3 | Example 4 | Example 5 | Example 6 |
| Mirabegron | 25 | 25 | 25 | 25 | 25 | 25 |
| Hydroxypropyl methylcellulose | 50 | 40 | 50 | 50 | 40 | 50 |
| Sodium alginate | 50 | 50 | 50 | 50 | 50 | 50 |
| Polyethylene glycol | 30 | 100 | 80 | 100 | 80 | 45 |
| |
100 | 30 | 30 | 30 | 30 | 55 |
| Hydroxypropyl cellulose | 7.5 | 7.5 | 7.5 | 7.5 | 7.5 | 7.5 |
| Magnesium stearate | 2.5 | 2.5 | 2.5 | 2.5 | 2.5 | 2.5 |
| Coating premix | 7.5 | 7.5 | 7.5 | 7.5 | 7.5 | 7.5 |
| In total | 272.5 | 262.5 | 252.5 | 272.5 | 242.5 | 272.5 |
In the formulations of the mirabegron sustained release tablets of the examples 1-6, the number average molecular weight of the polyethylene glycol is 5000-10000. The preparation method of the mirabegron sustained release tablet with the formula of the above examples 1-6 comprises the following steps:
(1) weighing polyethylene glycol and stearic acid according to the prescription amount, crushing by using a traditional Chinese medicine crusher, sieving all the crushed materials by using a 100-mesh sieve, weighing hydroxypropyl methylcellulose, sodium alginate and mirabegron according to the prescription amount, manually mixing the weighed materials for 10min, and sieving the mixture to obtain the premix.
(2) Dissolving a prescribed amount of hydroxypropyl cellulose in a proper amount of water to prepare a binder solution, adding the premix obtained in the step (1) into a fluidized bed, and spraying the binder solution to granulate in one step.
(3) And (3) adding magnesium stearate into the granules prepared in the step (2) and uniformly mixing to obtain total mixed granules.
(4) And (4) pressing the total mixed granules obtained in the step (3) into tablets.
(5) Dissolving the stomach-soluble film coating premix in the prescription amount in purified water to prepare uniform coating suspension, transferring the plain tablets obtained in the step (4) into a coating pot, and spraying the coating suspension to obtain the mirabegron sustained-release tablets.
To illustrate the better effect of using polyethylene glycol as an erodible slow-release matrix material together with stearic acid, the present invention provides comparative examples 1-2 in which only one of the two formulations is included.
Comparative examples 1-2 formulations of mirabegron sustained release tablets are shown in the following table (unit: g):
the preparation method of the mirabegron sustained release tablet with the formula of the comparative examples 1-2 comprises the following steps:
(1) weighing polyethylene glycol or stearic acid according to the prescription amount, crushing by using a traditional Chinese medicine crusher, sieving with a 100-mesh sieve, weighing hydroxypropyl methylcellulose, sodium alginate and mirabegron according to the prescription amount, manually mixing for 10min, and sieving to obtain the premix.
(2) Dissolving a prescribed amount of hydroxypropyl cellulose in a proper amount of water to prepare a binder solution, adding the premix obtained in the step (1) into a fluidized bed, and spraying the binder solution to granulate in one step.
(3) And (3) adding magnesium stearate into the granules prepared in the step (2) and uniformly mixing to obtain total mixed granules.
(4) And (4) pressing the total mixed granules obtained in the step (3) into tablets.
(5) Dissolving the stomach-soluble film coating premix in the prescription amount in purified water to prepare uniform coating suspension, transferring the plain tablets obtained in the step (4) into a coating pot, and spraying the coating suspension to obtain the mirabegron sustained-release tablets.
Test example 1
Dissolution test
According to the Chinese pharmacopoeia dissolution test, the mirabegron sustained release tablets prepared in examples 1-6 and comparative examples 1-2 and the purchased original product (trade name of Myrbetriq, specification of 25mg, certified person of Astelas Pharma Technologies) were subjected to dissolution test in 900mL of phosphate buffer solution with pH6.8 at 37 ℃ by 100 rpm paddle method.
The results of cumulative release of mirabegron over time are shown in figure 1 and table 1.
TABLE 1
As can be seen from the table above, the dissolution rate of the example of the invention is obviously better than that of the comparative example and the original product, and compared with the comparative example 1 using polyethylene glycol alone, the comparative example 2 using stearic acid alone and the original product, the dissolution rate of the invention is more complete and can reach more than 99% optimally.
Test example 2
Stability test
The mirabegron sustained release tablets obtained in example 4 and comparative example 1 were respectively placed at 40 ℃. + -. 2 ℃ and 75%. + -. 5% relative humidity for 6 months, and samples were taken at 0 month, 3 months and 6 months respectively for HPLC detection to determine the contents of the substances, and the results are shown in Table 2.
TABLE 2
As can be seen from the data in table 2, the total impurity content of the mirabegron sustained release tablet obtained in example 4 changes only by 0.08% in the process of being placed for 6 months, while the maximum impurity content of the mirabegron sustained release tablet obtained in comparative example 1 increases by nearly 4 times and the total impurity content increases by nearly 3 times compared with 0 month after being placed for 6 months.
Claims (8)
1. The mirabegron sustained-release tablet is characterized in that the mirabegron sustained-release tablet comprises the following components in parts by weight:
2. the mirabegron sustained release tablet of claim 1, wherein the polyethylene glycol has a number average molecular weight of 5000 to 10000.
3. The mirabegron sustained-release tablet of claim 1, wherein the weight ratio of the hydroxypropyl cellulose to the sodium alginate is preferably 1 (0.2-5), and more preferably 1 (0.5-2).
4. The mirabegron sustained-release tablet according to claim 1, wherein the weight ratio of the polyethylene glycol to the stearic acid is preferably 10 (1-7), more preferably 10: (2-5).
5. The mirabegron sustained-release tablet of claim 1, wherein the mirabegron sustained-release tablet comprises the following components in parts by weight:
6. the mirabegron sustained-release tablet of claim 1, wherein the mirabegron sustained-release tablet comprises the following components in parts by weight:
7. a preparation method of the mirabegron sustained release tablet as claimed in any one of claims 1 to 6, which is characterized by comprising the following steps:
(1) pretreatment: weighing polyethylene glycol and stearic acid according to the prescription amount, crushing and sieving, weighing hydroxypropyl methylcellulose, sodium alginate and mirabegron according to the prescription amount, mixing and sieving;
(2) one-step granulation by a fluidized bed: dissolving a prescribed amount of hydroxypropyl cellulose in a proper amount of water to prepare a binder solution, adding the premix obtained in the step (1) into a fluidized bed, and spraying the binder solution to granulate in one step;
(3) total mixing: adding the granules prepared in the step (2) into magnesium stearate and uniformly mixing;
(4) tabletting: pressing the total mixed particles obtained in the step (3) into tablets;
(5) coating: and (3) dissolving the stomach-soluble film coating premix with the prescription amount in purified water to prepare uniform suspension, transferring the plain tablets obtained in the step (4) into a coating pot, and spraying the coating suspension to obtain the mirabegron sustained-release tablets.
8. The method of claim 7, wherein the step (1) of sieving is 100 mesh sieving.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210549286.3A CN114983956A (en) | 2022-05-20 | 2022-05-20 | Mirabegron sustained release tablet and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210549286.3A CN114983956A (en) | 2022-05-20 | 2022-05-20 | Mirabegron sustained release tablet and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN114983956A true CN114983956A (en) | 2022-09-02 |
Family
ID=83027412
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210549286.3A Pending CN114983956A (en) | 2022-05-20 | 2022-05-20 | Mirabegron sustained release tablet and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN114983956A (en) |
-
2022
- 2022-05-20 CN CN202210549286.3A patent/CN114983956A/en active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR101524164B1 (en) | Controlled release pharmaceutical composition | |
| KR101537200B1 (en) | Novel pharmaceutical composition | |
| CN107669683B (en) | Pharmaceutical composition containing sitagliptin and metformin | |
| CN105935358B (en) | One seed sand library is than bent Valsartan sustained release agent and preparation method thereof | |
| CN109875972B (en) | Olmesartan medoxomil and amlodipine pharmaceutical composition | |
| US20030104059A1 (en) | Controlled release tablets of metformin | |
| CN117442577B (en) | Candesartan cilexetil microchip and preparation method and application thereof | |
| CN117547534B (en) | Nicorandil sustained release preparation and preparation method thereof | |
| CN107998097B (en) | A kind of tablet and preparation method thereof containing olmesartan medoxomil | |
| CN112494485B (en) | Saxagliptin and metformin hydrochloride sustained-release tablet | |
| US6726929B1 (en) | Pharmaceutical mixture comprising a profen | |
| CN102764254B (en) | A kind of levetiracetam medicinal composition and preparation method thereof | |
| CN114983956A (en) | Mirabegron sustained release tablet and preparation method thereof | |
| CN118284415A (en) | Darotamine pharmaceutical composition and preparation method and application thereof | |
| CN107397733B (en) | Mirabegron sustained release tablet and preparation method thereof | |
| CN114886862A (en) | Compound hypoglycemic medicine preparation and its preparing method | |
| CN113456639B (en) | Anti-arrhythmia pharmaceutical composition and preparation method thereof | |
| CN113616613A (en) | Metformin-glipizide compound tablet for treating diabetes and preparation method thereof | |
| JP3116970B2 (en) | Sustained-release preparation of pemirolast potassium | |
| CA2355291C (en) | A pharmaceutical mixture comprising a profen | |
| CN111568873A (en) | Cyclobenzaprine solid oral preparation and preparation method thereof | |
| EP3738584B1 (en) | Granulate containing eslicarbazepine acetate, its production, pharmaceutical preparations containing it, and their use | |
| EP3936119A1 (en) | Pharmaceutical composition of prolyl hydroxylase inhibitor and preparation method therefor | |
| CN106491550B (en) | Sustained-release tablet containing quetiapine or pharmaceutically acceptable salt thereof and preparation method thereof | |
| CN115300472A (en) | Pharmaceutical composition and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20240119 Address after: 571127 Guilin Ocean Economic Development Zone, Meilan District, Haikou City, Hainan Province Applicant after: HAINAN POLY PHARM. Co.,Ltd. Applicant after: ZHEJIANG POLY PHARMACEUTICAL Co.,Ltd. Address before: 311199 No.78 Xinzhou Road, Yuhang Economic Development Zone, Hangzhou City, Zhejiang Province Applicant before: ZHEJIANG POLY PHARMACEUTICAL Co.,Ltd. Applicant before: Anhui Puli Pharmaceutical Co.,Ltd. Applicant before: HAINAN POLY PHARM. Co.,Ltd. |
|
| TA01 | Transfer of patent application right |