CN113398084A - Levetiracetam sustained release tablet and preparation method thereof - Google Patents
Levetiracetam sustained release tablet and preparation method thereof Download PDFInfo
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- CN113398084A CN113398084A CN202110753429.8A CN202110753429A CN113398084A CN 113398084 A CN113398084 A CN 113398084A CN 202110753429 A CN202110753429 A CN 202110753429A CN 113398084 A CN113398084 A CN 113398084A
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- levetiracetam
- die
- sustained
- tablet
- tabletting
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- HPHUVLMMVZITSG-ZCFIWIBFSA-N levetiracetam Chemical compound CC[C@H](C(N)=O)N1CCCC1=O HPHUVLMMVZITSG-ZCFIWIBFSA-N 0.000 title claims abstract description 65
- 229960004002 levetiracetam Drugs 0.000 title claims abstract description 65
- 239000007939 sustained release tablet Substances 0.000 title claims abstract description 46
- 238000002360 preparation method Methods 0.000 title claims abstract description 15
- 239000000203 mixture Substances 0.000 claims abstract description 29
- 239000000945 filler Substances 0.000 claims abstract description 22
- 239000000314 lubricant Substances 0.000 claims abstract description 21
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 19
- 238000013268 sustained release Methods 0.000 claims abstract description 16
- 239000012730 sustained-release form Substances 0.000 claims abstract description 16
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims abstract description 14
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims abstract description 8
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 claims abstract description 8
- 239000004354 Hydroxyethyl cellulose Substances 0.000 claims abstract description 8
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- 235000019447 hydroxyethyl cellulose Nutrition 0.000 claims abstract description 8
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 claims abstract description 8
- 229920002451 polyvinyl alcohol Polymers 0.000 claims abstract description 8
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- 239000001267 polyvinylpyrrolidone Substances 0.000 claims abstract description 8
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- OKMWKBLSFKFYGZ-UHFFFAOYSA-N 1-behenoylglycerol Chemical compound CCCCCCCCCCCCCCCCCCCCCC(=O)OCC(O)CO OKMWKBLSFKFYGZ-UHFFFAOYSA-N 0.000 claims abstract description 7
- 229940049654 glyceryl behenate Drugs 0.000 claims abstract description 7
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- 125000005456 glyceride group Chemical group 0.000 claims abstract description 5
- 239000011734 sodium Substances 0.000 claims abstract description 5
- 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 4
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- 229920001661 Chitosan Polymers 0.000 claims abstract description 4
- 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 4
- 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 4
- 229930195725 Mannitol Natural products 0.000 claims abstract description 4
- 229920002472 Starch Polymers 0.000 claims abstract description 4
- 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 4
- 229910000019 calcium carbonate Inorganic materials 0.000 claims abstract description 4
- 239000001768 carboxy methyl cellulose Substances 0.000 claims abstract description 4
- 239000004203 carnauba wax Substances 0.000 claims abstract description 4
- 235000013869 carnauba wax Nutrition 0.000 claims abstract description 4
- 239000008101 lactose Substances 0.000 claims abstract description 4
- 239000000594 mannitol Substances 0.000 claims abstract description 4
- 235000010355 mannitol Nutrition 0.000 claims abstract description 4
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims abstract description 4
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims abstract description 4
- 239000008107 starch Substances 0.000 claims abstract description 4
- 235000019698 starch Nutrition 0.000 claims abstract description 4
- 230000007246 mechanism Effects 0.000 claims description 74
- 239000003826 tablet Substances 0.000 claims description 16
- 238000002156 mixing Methods 0.000 claims description 13
- 239000000843 powder Substances 0.000 claims description 12
- 230000000630 rising effect Effects 0.000 claims description 11
- 238000000034 method Methods 0.000 claims description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 8
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- 238000009475 tablet pressing Methods 0.000 claims description 7
- 239000001856 Ethyl cellulose Substances 0.000 claims description 6
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 claims description 6
- 229920001249 ethyl cellulose Polymers 0.000 claims description 6
- 235000019325 ethyl cellulose Nutrition 0.000 claims description 6
- 229920000609 methyl cellulose Polymers 0.000 claims description 6
- 239000001923 methylcellulose Substances 0.000 claims description 6
- 235000010981 methylcellulose Nutrition 0.000 claims description 6
- 238000007670 refining Methods 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 235000021355 Stearic acid Nutrition 0.000 claims description 3
- 239000011248 coating agent Substances 0.000 claims description 3
- 238000000576 coating method Methods 0.000 claims description 3
- MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 claims description 3
- 229940057948 magnesium stearate Drugs 0.000 claims description 3
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 3
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 3
- 229940045902 sodium stearyl fumarate Drugs 0.000 claims description 3
- 239000008117 stearic acid Substances 0.000 claims description 3
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 abstract 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 abstract 1
- UKMSUNONTOPOIO-UHFFFAOYSA-M behenate Chemical compound CCCCCCCCCCCCCCCCCCCCCC([O-])=O UKMSUNONTOPOIO-UHFFFAOYSA-M 0.000 abstract 1
- 229940116224 behenate Drugs 0.000 abstract 1
- 229910052708 sodium Inorganic materials 0.000 abstract 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 abstract 1
- 239000001961 anticonvulsive agent Substances 0.000 description 4
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
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- 230000009471 action Effects 0.000 description 2
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- 206010015037 epilepsy Diseases 0.000 description 2
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- 206010067484 Adverse reaction Diseases 0.000 description 1
- 208000014644 Brain disease Diseases 0.000 description 1
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- 206010019233 Headaches Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
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- 238000005516 engineering process Methods 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 230000010224 hepatic metabolism Effects 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
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- 102000004169 proteins and genes Human genes 0.000 description 1
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- 230000009885 systemic effect Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Images
Classifications
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/4015—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
- A61J3/00—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
- A61J3/06—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms into the form of pills, lozenges or dragees
-
- 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
- A61K9/282—Organic compounds, e.g. fats
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
Abstract
The invention discloses a levetiracetam sustained-release tablet which is mainly prepared from the following components in parts by mass: 15-60% of levetiracetam, 10-80% of filler, 1-20% of sustained release agent and 1-5% of lubricant, wherein the filler is one or a mixture of at least two of starch, lactose, mannitol and calcium carbonate, and the sustained release agent is one or a mixture of more than two of polyvinylpyrrolidone (PVP), hydroxyethyl cellulose (HEC), octadecanol, glyceryl behenate, glyceride, carnauba wax, sodium carboxymethylcellulose (CMC-Na), polyvinyl alcohol (PVA), chitin and chitosan; the lubricant is one or a mixture of more than two of glyceride behenate, magnesium stearate and sodium hard fumarate; the levetiracetam sustained release tablet disclosed by the invention is simple in composition, good in strength, not easy to loosen, and quick and simple in preparation process.
Description
Technical Field
The invention belongs to the field of medicines, and particularly relates to a levetiracetam sustained-release tablet and a preparation method thereof.
Background
Epilepsy is the second most common disease of headache in neurology department, and the disease causes of congenital heredity, brain diseases, systemic diseases, etc. are all in the age range of infants, teenagers, adults and the elderly. There are currently a number of antiepileptic drugs with different mechanisms of action for therapeutic management, including levetiracetam. Levetiracetam has its unique advantages over traditional antiepileptic drugs. The oral preparation has the advantages of quick and complete oral absorption, low protein binding rate, good pharmacokinetic characteristics, high bioavailability, no need of liver metabolism, no interaction with other antiepileptic drugs, and is classified as a 'heavy pound bomb' drug in the antiepileptic drugs. Levetiracetam can be used for adults and also has higher curative effect and lower adverse reaction incidence when used for treating epilepsy patients of all ages. Simultaneously, the composition can also improve the immunologic function of the children patients and has certain effect on controlling the illness state.
Levetiracetam, with the molecular formula of C8H14N2O2 and the chemical name of (S) -alpha-ethyl-2-oxo-1-acetamide pyrrolidine, belongs to BCSIII, is a highly soluble and low-permeability drug, and is very soluble in water (104.0g/100 mL).
Disclosure of Invention
The invention aims to provide a levetiracetam sustained-release tablet and a preparation method thereof.
The technical scheme of the invention is that the levetiracetam sustained release tablet is mainly prepared from the following components in parts by mass: the composition comprises, by weight, 15-60% of levetiracetam, 10-80% of a filler, 1-20% of a sustained-release agent and 1-5% of a lubricant, wherein the filler is one or a mixture of at least two of starch, lactose, mannitol and calcium carbonate, and the sustained-release agent is one or a mixture of more than two of polyvinylpyrrolidone (PVP), Ethyl Cellulose (EC), Methyl Cellulose (MC), hydroxyethyl cellulose (HEC), octadecanol, glyceryl behenate, stearic acid, magnesium stearate, monostearate, glyceride, carnauba wax, sodium carboxymethylcellulose (CMC-Na), polyvinyl alcohol (PVA), chitin and chitosan; the lubricant is one or a mixture of more than two of glyceryl behenate, magnesium stearate and sodium stearyl fumarate.
Preferably, the levetiracetam sustained release tablet is mainly prepared from the following components in parts by mass: 20-40% of levetiracetam, 20-70% of filler, 2-5% of sustained-release agent and 1-3% of lubricant.
Preferably, the levetiracetam sustained release tablet is mainly prepared from the following components in parts by mass: 30-40% of levetiracetam, 50-60% of filler, 2-5% of sustained-release agent and 1-3% of lubricant.
A preparation method of levetiracetam sustained release tablets comprises the steps of firstly, mixing levetiracetam with a prescription amount and a filler with a prescription amount of 50% -60%, and fully and uniformly mixing for no less than 30 minutes to obtain a first mixture; then adding the slow release agent and the lubricant in the prescribed amount into the first mixture, and fully mixing to obtain a second mixture; then, fully mixing the rest filling agent with the second mixture for not less than 20 minutes to obtain powder of the levetiracetam sustained release tablet; and finally, tabletting the powder by tabletting equipment to obtain initial tablets, and coating the initial tablets to obtain the levetiracetam sustained-release tablets.
Preferably, the sheeting equipment includes film-making die disc, feeding mechanism and sheeting mechanism, be provided with interchange mechanism between feeding mechanism and the sheeting mechanism, interchange mechanism including exchange the support, with exchange support fixed mounting's pivot and drive the rotatory first motor of pivot, feeding mechanism and sheeting mechanism equally divide do not install with on the interchange support, first motor drive it is rotatory to exchange the support, make feeding mechanism and sheeting mechanism rotate successively to the die disc on, feed and preforming in proper order.
Preferably, the tabletting mold comprises a first mold and a second mold which are symmetrical about a rotating shaft, the feeding mechanism and the tabletting mechanism are adapted to the first mold and the second mold, and the rotating shaft rotates, so that the feeding mechanism and the tabletting mechanism are interchanged between the first mold and the second mold.
Preferably, the bottom of the first die disc and the bottom of the second die disc are respectively provided with a first supporting plate and a second supporting plate, the first supporting plate and the second supporting plate are respectively connected with a first rotary driving assembly and a second rotary driving assembly, and the first rotary driving assembly and the second rotary driving assembly respectively drive the first supporting plate and the second supporting plate to rotate so as to seal or open the bottom surfaces of the first die disc and the second die disc; and the bottoms of the first supporting plate and the second supporting plate are respectively provided with a first receiving hopper and a second receiving hopper.
Preferably, the interchange bracket is provided with two mounting through grooves with the inner diameter not smaller than the outer diameter of the sheet making die disc, and the feeding mechanism and the sheet pressing mechanism are respectively mounted in the two mounting through grooves; the feeding mechanism comprises a refining screen detachably arranged in the installation through groove and a refining vibrator connected with the refining screen; the tabletting mechanism comprises a pressure head arranged in the installation through groove and an air cylinder which is fixed on the interchange bracket and drives the pressure head to lift.
Preferably, the first die disc or the second die disc comprises a die disc body and a plurality of tabletting through holes arranged on the die disc body, the tabletting through holes comprise an upper horn hole and a lower cylindrical hole which are coaxially arranged, and the upper horn hole and the lower cylindrical hole are smoothly and excessively connected; the pressure head comprises a pressure rising and reducing plate and a die head arranged at the bottom of the pressure rising and reducing plate, the die head comprises a horn die head which is matched with the upper horn hole and a cylindrical die head which is matched with the lower cylindrical hole, all the horn die heads are connected into a whole and are connected with the pressure rising and reducing plate through nitrogen springs, a cylindrical hole which is matched with the cylindrical die head is formed in each horn die head, and the cylindrical die head penetrates through the cylindrical hole and is fixedly installed with the pressure rising and reducing plate.
Preferably, the upper horn holes are conical holes or rectangular cone holes, and the upper horn holes are uniformly distributed on the die disc body.
The levetiracetam sustained release tablet provided by the technical scheme of the invention has the beneficial effects that: the lubricant is added, so that the preparation of the levetiracetam sustained-release tablets is facilitated, the strength of the levetiracetam sustained-release tablets is increased, and the levetiracetam sustained-release tablets are prevented from loosening.
The preparation method of the levetiracetam sustained release tablet has the beneficial effects that: by mixing the filling agent in batches, the lubricant and the sustained-release agent can be mixed with the levetiracetam more smoothly and uniformly, and the strength and the fluidity of the levetiracetam sustained-release tablet are improved. In the preparation method, the tabletting equipment is simple to operate, the tabletting operation efficiency is high, and the tabletting effect is good.
Drawings
Figure 1 is a front view of a sheeting apparatus according to the present invention,
figure 2 is a perspective view of a sheeting apparatus according to the present invention,
figure 3 is a cross-sectional view of the sheeting die disc and ram,
figure 4 is a schematic view of a tabletting process,
figure 5 is a schematic view of another embodiment of the sheeting die and ram,
fig. 6 is a cross-sectional view of the die through-hole and die of fig. 5.
Detailed Description
In order to facilitate the understanding of the technical solutions of the present invention for those skilled in the art, the technical solutions of the present invention will be further described with reference to the drawings attached to the specification.
The technical scheme of the invention is that the levetiracetam sustained release tablet is mainly prepared from the following components in parts by mass: the composition comprises, by weight, 15-60% of levetiracetam, 10-80% of a filler, 1-20% of a sustained-release agent and 1-5% of a lubricant, wherein the filler is one or a mixture of at least two of starch, lactose, mannitol and calcium carbonate, and the sustained-release agent is one or a mixture of more than two of polyvinylpyrrolidone (PVP), Ethyl Cellulose (EC), Methyl Cellulose (MC), hydroxyethyl cellulose (HEC), octadecanol, glyceryl behenate, stearic acid, magnesium stearate, monostearate, glyceride, carnauba wax, sodium carboxymethylcellulose (CMC-Na), polyvinyl alcohol (PVA), chitin and chitosan; the lubricant is one or a mixture of more than two of glyceryl behenate, magnesium stearate and sodium stearyl fumarate.
According to the levetiracetam sustained-release tablet disclosed by the technical scheme of the invention, the lubricant is added, so that the preparation difficulty of the levetiracetam sustained-release tablet is reduced, the strength of the prepared levetiracetam sustained-release tablet is increased, and the levetiracetam sustained-release tablet is prevented from loosening.
A preparation method of levetiracetam sustained release tablets comprises the following steps: firstly, mixing levetiracetam with the prescription amount and a filling agent with the prescription amount of 50% -60%, and fully and uniformly mixing for no less than 30 minutes to obtain a first mixture. And secondly, adding the slow release agent and the lubricant in the prescribed amount into the first mixture, and fully mixing to obtain a second mixture. And thirdly, fully mixing the rest filling agent with the second mixture for not less than 20 minutes to obtain the levetiracetam sustained release tablet powder. And fourthly, tabletting the powder through tabletting equipment to obtain the initial tablet. And fifthly, coating the initial tablet to obtain the levetiracetam sustained release tablet.
In the steps of the method, the filling agent is mixed for several times, so that the lubricant and the sustained-release agent can be mixed with the levetiracetam more smoothly and uniformly, and the strength and the fluidity of the levetiracetam sustained-release tablet are improved.
In the above method, the tabletting equipment is shown in fig. 1 and fig. 2, and comprises a tabletting mold 1, a feeding mechanism 3 and a tabletting mechanism 4. An exchange mechanism 2 is arranged between the feeding mechanism 3 and the tabletting mechanism 4. The interchange mechanism 2 includes an interchange bracket 21, a rotation shaft 22 fixedly installed with the interchange bracket 21, and a first motor 23 driving the rotation shaft 22 to rotate. The feeding mechanism 3 and the tablet pressing mechanism 4 are respectively arranged on the interchange bracket 21, and the first motor 23 drives the interchange bracket 21 to rotate, so that the feeding mechanism 3 and the tablet pressing mechanism 4 sequentially rotate to the tablet making die disc 1 to sequentially perform feeding and tablet pressing.
Based on the technical scheme, the working principle of the tabletting equipment is as follows: interchanging support 21 and rotating, driving feeding mechanism 3 and sheeting mechanism 4 on it to rotate, when feeding mechanism 3 rotated to the film-making mold 1 on, feeding mechanism 2 added levetiracetam sustained-release tablet's powder in to the film-making mold 1, added after accomplishing, interchanging support 21 and rotated once more, sheeting mechanism 4 rotated to the film-making mold 1 on, sheeting mechanism 4 worked, realized the preforming.
Technical scheme and theory of operation above, this sheeting equipment, simple structure, the preforming operation is quick.
As shown in fig. 1 and 2, the tabletting mold 1 includes a first mold 11 and a second mold 12 which are symmetrical about a rotation axis 22 and have the same structure and size. The feeding mechanism 3 and the tabletting mechanism 4 are adapted to the first die plate 11 and the second die plate 12. The rotary shaft 22 is rotated so that the feeding mechanism 3 and the tablet pressing mechanism 4 are interchanged between the first die plate 11 and the second die plate 12. Through the arrangement of the first die plate 11 and the second die plate 12, the first die plate 11 and the second die plate 12 work simultaneously, the feeding mechanism 3 and the tabletting mechanism 4 work simultaneously, and for example, when the feeding mechanism 3 feeds the first die plate 11, the tabletting mechanism 4 performs tabletting work on the second die plate 12. This technical scheme's setting has improved work efficiency, and makes sheeting apparatus overall structure simple, convenient operation.
The first motor 23 is a servo motor, and sets its automatic operation time and the angle of each rotation to realize automatic intermittent rotation. And rotating after the primary feeding and tabletting work is finished.
As shown in fig. 1 and 2, the first and second mold plates 11 and 12 are provided at the bottom thereof with a first and second support plate 51 and 52, respectively. The first and second pallets 51 and 52 are respectively connected with a first and second rotary driving assembly 54 and 53. The first rotary driving assembly 54 and the second rotary driving assembly 53 respectively drive the first supporting plate 51 and the second supporting plate 52 to rotate so as to close or open the bottom surfaces of the first die plate 11 and the second die plate 12. The bottoms of the first supporting plate 51 and the second supporting plate 52 are also respectively provided with a first receiving hopper 61 and a second receiving hopper 62. The upper parts of the first die plate 11 and the second die plate 12 are respectively provided with a first feeding hopper and a second feeding hopper. First feeder hopper and second feeder hopper all set up on feed mechanism 3 and 4 upper portions of preforming mechanism, avoid taking place to interfere with feed mechanism 3 and preforming mechanism 4. After the feeding mechanism 3 rotates to the first die plate 11 and the second die plate 12, the first feeding hopper and the second feeding hopper input materials into the feeding mechanism respectively.
As shown in fig. 2, the first rotation driving assembly 54 and the second rotation driving assembly 53 have the same structure, but do not rotate simultaneously, and each of the first rotation driving assembly and the second rotation driving assembly includes a connecting shaft fixed to the first supporting plate 51 and the second supporting plate 52, a second rotation motor is connected to the connecting shaft, the two connecting shafts are respectively disposed at the outer sides of the first supporting plate 51 and the second supporting plate 52, and the second rotation motor operates, so that the first supporting plate 51 and the second supporting plate 52 rotate around the two connecting shafts. When feeding or tabletting is carried out on the first die disc 11 and the second die disc 12, the bottom ends of the first die disc 11 and the second die disc 12 are respectively sealed by the first supporting plate 51 and the second supporting plate 52, after tabletting is finished, the first supporting plate 51 or the second supporting plate 52 rotates to open the bottoms of the first die disc 11 and the second die disc 12, so that tablets pressed in the first die disc 11 and the second die disc 12 can fall from the bottoms, a paper scrap process is completed, and after the tablets fall, the first supporting plate 51 or the second supporting plate 52 returns again.
The first rotary driving assembly 54 and the second rotary driving assembly 53 in the present technology are separately controlled to rotate independently, and only rotate after the tablet pressing is completed.
As shown in fig. 2, the interchangeable holder 21 is provided with two mounting through slots 24 and 25 having an inner diameter not smaller than the outer diameter of the tableting die disc 1. The feeding mechanism 3 and the tabletting mechanism 4 are respectively arranged in the two mounting through grooves 24 and 25. The feeding mechanism 3 comprises a homogenizing screen 31 which is detachably arranged in the installation through groove 24 and a homogenizing vibrator 32 which is connected with the homogenizing screen 31. The sheeting mechanism 4 comprises a pressure head 41 arranged in the installation through groove 25 and an air cylinder 42 which is fixed on the interchanging bracket 21 and drives the pressure head 41 to lift. The arrangement of the through groove 24 provides positions for the feeding mechanism 3 and the tablet pressing mechanism 4 to avoid interference, and reduces the weight of the interchange bracket 21 to keep the interchange mechanism 2 balanced. At least two support bars 26 are arranged at the bottom of the interchangeable holder 21, and the bottom of the support bars 26 are in contact with the frame 7 and rotatably slide along the frame 7 to ensure the balance of the interchangeable holder 21.
As shown in fig. 2 to 4, each of the first die plate 11 and the second die plate 12 includes a die plate body 111 and a plurality of pressing through holes 13 disposed on the die plate body 111. The tablet through hole 13 includes an upper flared hole 131 and a lower cylindrical hole 132 that are coaxially disposed. The upper bell hole 131 and the lower cylindrical hole 132 are smoothly connected. The arrangement of the upper horn hole 131 in the tabletting through hole 13 is convenient for the homogenizing sieve 31 to sieve powder materials into the tabletting through hole 13, and the inlet range is enlarged.
The ram 41 includes a pressure rising and lowering plate 411, and a die head 412 disposed at the bottom of the pressure rising and lowering plate 411. The die 412 includes a horn die 4121 corresponding to the upper horn aperture 131 and a cylindrical die 4122 corresponding to the lower cylindrical aperture 132. All horn dies 4121 are connected as a unit and connected to the pressure increasing and decreasing plate 411 by a nitrogen spring 413. The horn die head 4121 is provided with a cylindrical hole corresponding to the cylindrical die head 4122, and the cylindrical die head 4122 penetrates through the cylindrical hole to be fixedly installed with the pressure rising and reducing plate 411.
In operation, as shown in fig. 4, the horn die 4121 and the cylindrical die 4122 move downward synchronously, the horn die 4121 collects the powder in the upper horn hole 131 downward and presses the powder into the lower cylindrical hole 132, then the cylindrical die 4122 continues to move downward under the action of the lifting pressing plate 411, at this time, the horn die 4121 stops moving downward continuously under the retraction of the nitrogen spring 413, and the cylindrical die 4122 compacts the powder in the lower cylindrical hole 132 and prepares a tablet. After the film-making, go up and down to press plate 411 and suspend to push down, keep the state after the film-making, then first layer board 51 or second layer board 52 of this die disc body 111 bottom are rotatory, give way this die disc body 111 bottom surface, then go up and down to press plate 411 and can continue to push down for the tablet of suppression falls down by this die disc body 111 bottom, accomplishes once the film-making, then the rotatory resetting of first layer board 51 or second layer board 52 of this die disc body 111 lower part.
Referring to fig. 3 and 4, which illustrate an embodiment of the die 412 and the preform through-holes 13, in fig. 3 and 4, the trumpet die 4121 of the die 412 has a conical shape and the upper trumpet hole 131 has a conical shape. As shown in FIGS. 5 and 6, another embodiment of the die 412 and the preform through-holes 13 is shown, in which the upper flared opening 131A is a rectangular tapered opening and the flared die 4121A is fitted into the upper flared opening 131A. Among this technical scheme, preforming through-hole 13 equipartition is arranged on die disc body 111, and when being the rectangle taper hole for last bellmouth 131A, the distance reduces between the two adjacent bellmouth 131A, and the blank area is less, and the powder stops on die disc body 111 upper surface less.
The levetiracetam sustained-release tablet of the technical scheme of the invention can also be prepared from the following components in parts by mass: 20-40% of levetiracetam, 20-70% of filler, 2-5% of sustained-release agent and 1-3% of lubricant.
The levetiracetam sustained release tablet of the technical scheme of the invention can also be prepared from the following components in parts by mass: 30-40% of levetiracetam, 50-60% of filler, 2-5% of sustained-release agent and 1-3% of lubricant.
The levetiracetam sustained-release tablet is applied to different patients according to different contents of main active ingredients, namely the levetiracetam, in the sustained-release tablet, and is more specific.
Technical solution of the invention is described above with reference to the accompanying drawings, it is obvious that the specific implementation of the invention is not limited by the above-mentioned manner, and it is within the scope of the invention to adopt various insubstantial modifications of the inventive method concept and technical solution, or to apply the inventive concept and technical solution to other occasions without modification.
Claims (10)
1. The levetiracetam sustained-release tablet is characterized by being mainly prepared from the following components in parts by mass: the composition comprises, by weight, 15-60% of levetiracetam, 10-80% of a filler, 1-20% of a sustained-release agent and 1-5% of a lubricant, wherein the filler is one or a mixture of at least two of starch, lactose, mannitol and calcium carbonate, and the sustained-release agent is one or a mixture of more than two of polyvinylpyrrolidone (PVP), Ethyl Cellulose (EC), Methyl Cellulose (MC), hydroxyethyl cellulose (HEC), octadecanol, glyceryl behenate, stearic acid, magnesium stearate, monostearate, glyceride, carnauba wax, sodium carboxymethylcellulose (CMC-Na), polyvinyl alcohol (PVA), chitin and chitosan; the lubricant is one or a mixture of more than two of glyceryl behenate, magnesium stearate and sodium stearyl fumarate.
2. The levetiracetam sustained-release tablet of claim 1, wherein the levetiracetam sustained-release tablet is mainly prepared from the following components in parts by mass: 20-40% of levetiracetam, 20-70% of filler, 2-5% of sustained-release agent and 1-3% of lubricant.
3. The levetiracetam sustained-release tablet of claim 2, wherein the levetiracetam sustained-release tablet is mainly prepared from the following components in parts by mass: 30-40% of levetiracetam, 50-60% of filler, 2-5% of sustained-release agent and 1-3% of lubricant.
4. A preparation method of levetiracetam sustained release tablets is characterized by comprising the steps of mixing levetiracetam in a prescription amount with a filling agent in an amount of 50% -60% of the prescription amount, and fully and uniformly mixing for no less than 30 minutes to obtain a first mixture; then adding the slow release agent and the lubricant in the prescribed amount into the first mixture, and fully mixing to obtain a second mixture; then, fully mixing the rest filling agent with the second mixture for not less than 20 minutes to obtain powder of the levetiracetam sustained release tablet; and finally, tabletting the powder by tabletting equipment to obtain initial tablets, and coating the initial tablets to obtain the levetiracetam sustained-release tablets.
5. The method for preparing the levetiracetam sustained release tablet according to claim 4, wherein the tabletting equipment comprises a tablet making die disc, a feeding mechanism and a tabletting mechanism, an exchange mechanism is arranged between the feeding mechanism and the tabletting mechanism, the exchange mechanism comprises an exchange bracket, a rotating shaft fixedly mounted with the exchange bracket and a first motor for driving the rotating shaft to rotate, the feeding mechanism and the tabletting mechanism are respectively mounted on the exchange bracket, and the first motor drives the exchange bracket to rotate, so that the feeding mechanism and the tabletting mechanism sequentially rotate to the tablet making die disc for feeding and tabletting sequentially.
6. The method for preparing levetiracetam sustained release tablets according to claim 5, wherein the tablet-making die comprises a first die and a second die that are symmetrical about a rotation axis, the feeding mechanism and the tablet-making mechanism are adapted to the first die and the second die, and the rotation axis is rotated so that the feeding mechanism and the tablet-making mechanism are interchanged between the first die and the second die.
7. The preparation method of the levetiracetam sustained-release tablet according to claim 6, wherein a first supporting plate and a second supporting plate are respectively arranged at the bottoms of the first mold plate and the second mold plate, a first rotary driving assembly and a second rotary driving assembly are respectively connected to the first supporting plate and the second supporting plate, and the first rotary driving assembly and the second rotary driving assembly respectively drive the first supporting plate and the second supporting plate to rotate so as to realize the closing or opening of the bottom surfaces of the first mold plate and the second mold plate; and the bottoms of the first supporting plate and the second supporting plate are respectively provided with a first receiving hopper and a second receiving hopper.
8. The method for preparing the levetiracetam sustained-release tablet according to claim 5, wherein the interchange bracket is provided with two installation through grooves with the inner diameter not less than the outer diameter of a tablet-making mold disc, and the feeding mechanism and the tablet-pressing mechanism are respectively arranged in the two installation through grooves; the feeding mechanism comprises a refining screen detachably arranged in the installation through groove and a refining vibrator connected with the refining screen; the tabletting mechanism comprises a pressure head arranged in the installation through groove and an air cylinder which is fixed on the interchange bracket and drives the pressure head to lift.
9. The method for preparing the levetiracetam sustained-release tablet according to claim 8, wherein the first mold or the second mold comprises a mold body and a plurality of tablet through holes arranged on the mold body, the tablet through holes comprise an upper horn hole and a lower cylindrical hole which are coaxially arranged, and the upper horn hole and the lower cylindrical hole are smoothly and excessively connected; the pressure head comprises a pressure rising and reducing plate and a die head arranged at the bottom of the pressure rising and reducing plate, the die head comprises a horn die head which is matched with the upper horn hole and a cylindrical die head which is matched with the lower cylindrical hole, all the horn die heads are connected into a whole and are connected with the pressure rising and reducing plate through nitrogen springs, a cylindrical hole which is matched with the cylindrical die head is formed in each horn die head, and the cylindrical die head penetrates through the cylindrical hole and is fixedly installed with the pressure rising and reducing plate.
10. The preparation method of the levetiracetam sustained-release tablet according to claim 9, wherein the upper horn holes are conical holes or rectangular conical holes, and the upper horn holes are uniformly distributed on the die disc body.
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| CN202110753429.8A CN113398084A (en) | 2021-07-02 | 2021-07-02 | Levetiracetam sustained release tablet and preparation method thereof |
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| CN202110753429.8A CN113398084A (en) | 2021-07-02 | 2021-07-02 | Levetiracetam sustained release tablet and preparation method thereof |
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