CN100571687C - A kind of double sodium valproate orally disintegrating tablets and preparation method thereof - Google Patents
A kind of double sodium valproate orally disintegrating tablets and preparation method thereof Download PDFInfo
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- CN100571687C CN100571687C CNB2007101076898A CN200710107689A CN100571687C CN 100571687 C CN100571687 C CN 100571687C CN B2007101076898 A CNB2007101076898 A CN B2007101076898A CN 200710107689 A CN200710107689 A CN 200710107689A CN 100571687 C CN100571687 C CN 100571687C
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- NIJJYAXOARWZEE-UHFFFAOYSA-N di-n-propyl-acetic acid Natural products CCCC(C(O)=O)CCC NIJJYAXOARWZEE-UHFFFAOYSA-N 0.000 title claims abstract description 32
- 229940084026 sodium valproate Drugs 0.000 title claims abstract description 25
- AEQFSUDEHCCHBT-UHFFFAOYSA-M sodium valproate Chemical compound [Na+].CCCC(C([O-])=O)CCC AEQFSUDEHCCHBT-UHFFFAOYSA-M 0.000 title claims abstract description 25
- 239000006191 orally-disintegrating tablet Substances 0.000 title claims abstract description 21
- 238000002360 preparation method Methods 0.000 title claims abstract description 14
- 229940028937 divalproex sodium Drugs 0.000 claims abstract description 24
- MSRILKIQRXUYCT-UHFFFAOYSA-M valproate semisodium Chemical group [Na+].CCCC(C(O)=O)CCC.CCCC(C([O-])=O)CCC MSRILKIQRXUYCT-UHFFFAOYSA-M 0.000 claims abstract description 24
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 23
- 239000002671 adjuvant Substances 0.000 claims abstract description 22
- 239000004925 Acrylic resin Substances 0.000 claims abstract description 19
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 claims abstract description 12
- 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 12
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 claims abstract description 12
- 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 12
- 229930195725 Mannitol Natural products 0.000 claims abstract description 12
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims abstract description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims abstract description 12
- 229940109275 cyclamate Drugs 0.000 claims abstract description 12
- HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical compound OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000008101 lactose Substances 0.000 claims abstract description 12
- 239000000594 mannitol Substances 0.000 claims abstract description 12
- 235000010355 mannitol Nutrition 0.000 claims abstract description 12
- 229940041616 menthol Drugs 0.000 claims abstract description 12
- 239000008108 microcrystalline cellulose Substances 0.000 claims abstract description 12
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims abstract description 12
- 229940016286 microcrystalline cellulose Drugs 0.000 claims abstract description 12
- 239000000741 silica gel Substances 0.000 claims abstract description 12
- 229910002027 silica gel Inorganic materials 0.000 claims abstract description 12
- 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 7
- 238000005303 weighing Methods 0.000 claims description 20
- 239000003826 tablet Substances 0.000 claims description 19
- 239000000945 filler Substances 0.000 claims description 7
- 239000000203 mixture Substances 0.000 claims description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 5
- 229960000935 dehydrated alcohol Drugs 0.000 claims description 5
- 238000005469 granulation Methods 0.000 claims description 5
- 230000003179 granulation Effects 0.000 claims description 5
- 239000006166 lysate Substances 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 5
- 238000009702 powder compression Methods 0.000 claims description 5
- 238000010298 pulverizing process Methods 0.000 claims description 5
- 239000002994 raw material Substances 0.000 claims description 5
- 239000008187 granular material Substances 0.000 claims description 3
- 239000000463 material Substances 0.000 claims description 2
- 206010015037 epilepsy Diseases 0.000 abstract description 14
- 239000003814 drug Substances 0.000 abstract description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 10
- 206010026749 Mania Diseases 0.000 abstract description 6
- 208000019695 Migraine disease Diseases 0.000 abstract description 6
- 206010027599 migraine Diseases 0.000 abstract description 6
- 230000002265 prevention Effects 0.000 abstract description 6
- 208000019505 Deglutition disease Diseases 0.000 abstract description 5
- 210000000214 mouth Anatomy 0.000 description 10
- 239000001961 anticonvulsive agent Substances 0.000 description 4
- 230000003556 anti-epileptic effect Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 210000001035 gastrointestinal tract Anatomy 0.000 description 3
- 206010007247 Carbuncle Diseases 0.000 description 2
- 241001597008 Nomeidae Species 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000001037 epileptic effect Effects 0.000 description 2
- 238000010579 first pass effect Methods 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 229940126701 oral medication Drugs 0.000 description 2
- 229960002790 phenytoin sodium Drugs 0.000 description 2
- 210000003296 saliva Anatomy 0.000 description 2
- FJPYVLNWWICYDW-UHFFFAOYSA-M sodium;5,5-diphenylimidazolidin-1-ide-2,4-dione Chemical compound [Na+].O=C1[N-]C(=O)NC1(C=1C=CC=CC=1)C1=CC=CC=C1 FJPYVLNWWICYDW-UHFFFAOYSA-M 0.000 description 2
- 229960000604 valproic acid Drugs 0.000 description 2
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- 208000020925 Bipolar disease Diseases 0.000 description 1
- 241000167880 Hirundinidae Species 0.000 description 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 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 230000001773 anti-convulsant effect Effects 0.000 description 1
- 229960003965 antiepileptics Drugs 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- FFGPTBGBLSHEPO-UHFFFAOYSA-N carbamazepine Chemical compound C1=CC2=CC=CC=C2N(C(=O)N)C2=CC=CC=C21 FFGPTBGBLSHEPO-UHFFFAOYSA-N 0.000 description 1
- 229960000623 carbamazepine Drugs 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 229940075925 depakote Drugs 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 210000001156 gastric mucosa Anatomy 0.000 description 1
- 230000005802 health problem Effects 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 229960001848 lamotrigine Drugs 0.000 description 1
- PYZRQGJRPPTADH-UHFFFAOYSA-N lamotrigine Chemical compound NC1=NC(N)=NN=C1C1=CC=CC(Cl)=C1Cl PYZRQGJRPPTADH-UHFFFAOYSA-N 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- -1 need not to chew Substances 0.000 description 1
- 229960001816 oxcarbazepine Drugs 0.000 description 1
- CTRLABGOLIVAIY-UHFFFAOYSA-N oxcarbazepine Chemical compound C1C(=O)C2=CC=CC=C2N(C(=O)N)C2=CC=CC=C21 CTRLABGOLIVAIY-UHFFFAOYSA-N 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 229940083542 sodium Drugs 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 210000004916 vomit Anatomy 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a kind of double sodium valproate orally disintegrating tablets and preparation method thereof, its principal agent is a divalproex sodium, and adjuvant is microcrystalline Cellulose, mannitol, lactose, polyacrylic resin II, crospolyvinylpyrrolidone, cyclamate, menthol, micropowder silica gel.Double sodium valproate orally disintegrating tablets of the present invention can effectively be treated epilepsy, mania and prevention migraine, and taking convenience, and mouthfeel is good, and disintegrate is rapid, absorbs soon the bioavailability height.Take medicine to the patient of old man, children's or dysphagia and the inconvenient person that fetches water convenience is provided.
Description
One, technical field
The present invention relates to a kind of oral drug preparation for the treatment of epilepsy, mania and prevention of migraine and preparation method thereof, particularly relate to good double sodium valproate orally disintegrating tablets of a kind of disintegrate rapidly, release and mouthfeel and preparation method thereof.
Two, background technology
Divalproex sodium is the valproic acid class derivant of a new generation, is mainly used in treatment epilepsy, mania and prevention migraine clinically.Epilepsy is a main worldwide health problem, and it approximately affects 1%～2% of world population.The world has 4,000 ten thousand epilepsy (EP) patients at present, nearly 6,000,000 epileptics of China, and 380,000 newfound epileptics are arranged every year.Wherein in the majority with child and teenager, bigger to the mankind's harm.From a few days ago on, the best means of treatment epilepsy still is the anti-insane carbuncle medicine of prolonged application.
The insane carbuncle of Drug therapy has over one hundred year history.The antiepileptic that went on the market in the past in 1978 is called epilepsy medicine commonly used (tradition or classical antiepileptic), mainly contains phenytoin Sodium, valproic acid, carbamazepine.Phenytoin Sodium is serious because of untoward reaction, has withdrawed from a line medicine.Later listing person was called new antiepileptic in 1993, and ester, lamotrigine and oxcarbazepine are adjoined in the holder that only has of listing at home a few days ago.Epilepsy has polytype, and different outbreak types need different pharmaceutical.Because sodium valproate is all effective to various types of epilepsies, when the epilepsy type be can not determine, sodium valproate was a kind of selection safely and effectively.
Divalproex sodium is a valproic acid class derivant of new generation, by etc. the valproic acid of mol ratio and the low polymer that sodium valproate is formed.Its anti-convulsant activity is identical with sodium valproate.With Depakote be the double sodium valproate orally disintegrating tablets of trade name to get permission to be used for the treatment of epilepsy the earliest be in nineteen eighty-three, be used for the treatment of manic type bipolar disorder disease and prevention of migraine nineteen ninety-five and 1996 through U.S. food and FAD (FDA) approval subsequently.At present, the domestic sale divalproex sodium of also not going public.
The divalproex sodium preparation that has gone on the market abroad at present has enteric coatel tablets and two kinds of dosage forms of slow releasing tablet.But it is not very convenient that these two kinds of dosage forms are used for the patient of old man, children's or dysphagia.Oral cavity disintegration tablet can not need water or only need use low amounts of water, need not to chew, and tablet places lingual surface, after the rapid disintegrate of chance saliva, borrows and swallows power, and medicine can absorb onset rapidly.Compare with conventional tablet, oral cavity disintegration tablet has the following advantages: 1. absorption is fast, bioavailability is high.2. taking convenience: oral cavity disintegration tablet needn't be used water delivery service, and saliva can make its disintegrate or dissolving, can swallow by common dose, can be placed in the water again to take after the disintegrate, can also not need to take medicine with water swallow.Be particularly useful for the patient of old man, children's's dysphagia and the inconvenient person that fetches water takes medicine; 3. intestinal is residual few, and the low medicine of side effect arrives the gastrointestinal tract rapid disintegrate of energy before and is dispersed into trickle granule, causes medicine to distribute in the gastrointestinal tract large tracts of land, and absorption point increases, thereby has reduced medicine to the gastrointestinal local excitation.4. avoid the first pass effect of liver: because oral cavity disintegration tablet rapidly disintegrate in mouth except that major part enters the gastrointestinal tract with swallowing act, also has considerable part to absorb through the oral cavity, thereby rapid-action, first pass effect is little.
Oral cavity disintegration tablet develops by its unique characteristics rapidly, becomes the emphasis of tablet exploitation.Oral cavity disintegration tablet is applicable to old people and child's oral medication, especially has more suitable use advantage for gulping down the cancer chemotherapy patient that water promptly vomits, thereby has found a kind of way of solution for the quality of life of improving patient; Medical treatment for special circumstances such as the geologist of field work drinking-water inconvenience and desert area people provides convenience in addition.
Three, summary of the invention
The object of the present invention is to provide a kind of taking convenience, mouthfeel is good, and disintegrate is rapid, absorbs soon double sodium valproate orally disintegrating tablets that bioavailability is high and preparation method thereof.
Purpose of the present invention can realize by following measure:
Double sodium valproate orally disintegrating tablets comprises principal agent and adjuvant, it is characterized in that by following percentage by weight formulated: principal agent 10%-30%, adjuvant 70%-90%.
Principal agent of the present invention is a divalproex sodium, by name pair-(2-Propylpentanoic) hydrogen sodium of its chemistry, and molecular formula is C
16H
31NaO
4Molecular weight: 310.37, its structural formula is as follows:
Adjuvant of the present invention is formulated by following percentage by weight:
A. microcrystalline Cellulose 10-30%
B. mannitol 10-60%
C. lactose 0-30%
D. polyacrylic resin II 0-15%
E. crospolyvinylpyrrolidone 3-10%
F. cyclamate 1-5%
G. menthol 0.1-1%
H. micropowder silica gel 0.5-3%
Wherein lactose, mannitol are filler, and microcrystalline Cellulose, crospolyvinylpyrrolidone are disintegrating agent, and polyacrylic resin II, cyclamate and menthol are correctives, and micropowder silica gel is a fluidizer.
2. the preparation method of double sodium valproate orally disintegrating tablets according to claim 1 comprises raw material pulverizing, weighing mixing, granulation, sheeting process.It is characterized in that, comprise following concrete processing step:
Step 1: with divalproex sodium and various adjuvant pulverize separately, cross the 80-100 mesh sieve then, preserve standby respectively;
Step 2: take by weighing polyacrylic resin II by recipe quantity, add dehydrated alcohol and make its dissolving in right amount, take by weighing divalproex sodium by recipe quantity and add in this lysate, dry under the 40-50 ℃ of temperature, take out and pulverize, cross the 80-100 mesh sieve, standby;
Step 3: take by weighing other adjuvant in filler, disintegrating agent and the accessory formula by accessory formula, and with its abundant mix homogeneously;
Step 4: with the granule and the abundant mix homogeneously of the mixed uniformly component of step 3 of step 2;
Step 5: the mixed uniformly component of step 4 is sent into tablet machine, carry out direct powder compression.
The invention has the advantages that:
(1) the present invention fills a prescription rationally, and each adjuvant is cheap and easy to get, and good with the principal agent compatibility, preparation technology is simple, is applicable to large-scale industrial production;
(2) the double sodium valproate orally disintegrating tablets disintegrate that the present invention relates to is rapid, mouthfeel good, and the no grittiness that enters the mouth and cool taste do not have other uncomfortable taste yet;
(3) double sodium valproate orally disintegrating tablets of the present invention, its principal agent with enteric material polyacrylic resin II parcel, are used further to tabletting earlier; In the enteral dissolving, non-stimulated to gastric mucosa, gastrointestinal side effect is few after the disintegrate;
(4) double sodium valproate orally disintegrating tablets of the present invention can effectively be treated epilepsy, mania and prevention migraine, absorbs soon the bioavailability height.Take medicine to the patient of old man, children's or dysphagia and the inconvenient person that fetches water convenience is provided.
Below in conjunction with specific embodiment the present invention is further described.
The specific embodiment
Embodiment 1
Double sodium valproate orally disintegrating tablets comprises principal agent and adjuvant, it is characterized in that by following percentage by weight formulated: principal agent 10%, adjuvant 90%.
Divalproex sodium 25g (10%)
Microcrystalline Cellulose 37.5g (20%)
Mannitol 92.5g (37%)
Lactose 55g (22%)
Polyacrylic resin II 12.5g (5%)
Crospolyvinylpyrrolidone 7.5g (3%)
Cyclamate 2.5g (1%)
Menthol 2.5 (1%)
Micropowder silica gel 2.5 (1%)
Make 1000 altogether
Wherein lactose, mannitol are filler, and microcrystalline Cellulose, crospolyvinylpyrrolidone are disintegrating agent, and polyacrylic resin II, cyclamate and menthol are correctives, and micropowder silica gel is a fluidizer.
The preparation method of divalproex sodium of the present invention comprises raw material pulverizing, weighing mixing, granulation, sheeting process.It is characterized in that concrete processing step is as follows:
Step 1: divalproex sodium is reached and above-mentioned various adjuvant pulverize separately, cross 100 mesh sieves then, preserve standby respectively;
Step 2: take by weighing polyacrylic resin II by recipe quantity, add dehydrated alcohol and make its dissolving in right amount, take by weighing divalproex sodium by above-mentioned recipe quantity and add in this lysate, dry under 50 ℃ of temperature, take out and pulverize, cross 80 mesh sieves, standby;
Step 3: take by weighing residue each component and the abundant mix homogeneously of step 2 component in the prescription by above-mentioned recipe quantity;
Step 4: the component that step 3 mixes is sent into conventional tablet machine, carry out direct powder compression, make sheet and heavily be the double sodium valproate orally disintegrating tablets of 250mg.
Result of the test:
Tablet hardness: 30 ± 5N
Disintegration: 15～30s
Disintegrate in intraoral disintegration time limit and mouthfeel: the 40S, no grittiness, cool taste does not have uncomfortable taste
Embodiment 2
Double sodium valproate orally disintegrating tablets comprises principal agent and adjuvant, it is characterized in that by following percentage by weight formulated: principal agent 20%, adjuvant 80%.
Divalproex sodium 50g (20%)
Microcrystalline Cellulose 32.5g (13%)
Mannitol 110g (38%)
Lactose 45g (15%)
Polyacrylic resin II 12.5g (5%)
Crospolyvinylpyrrolidone 12.5g (5%)
Cyclamate 2.0g (1%)
Menthol 2.5 (1%)
Micropowder silica gel 5.0 (2%)
Make 1000 altogether
Wherein lactose, mannitol are filler, and microcrystalline Cellulose, crospolyvinylpyrrolidone are disintegrating agent, and polyacrylic resin II, cyclamate and menthol are correctives, and micropowder silica gel is a fluidizer.
The preparation method of divalproex sodium of the present invention comprises raw material pulverizing, weighing mixing, granulation, sheeting process.It is characterized in that concrete processing step is as follows:
Step 1: divalproex sodium is reached and above-mentioned various adjuvant pulverize separately, cross 100 mesh sieves then, preserve standby respectively;
Step 2: take by weighing polyacrylic resin II by recipe quantity, add dehydrated alcohol and make its dissolving in right amount, take by weighing divalproex sodium by above-mentioned recipe quantity and add in this lysate, dry under 50 ℃ of temperature, take out and pulverize, cross 80 mesh sieves, standby;
Step 3: take by weighing residue each component and the abundant mix homogeneously of step 2 component in the prescription by above-mentioned recipe quantity;
Step 4: the component that step 3 mixes is sent into conventional tablet machine, carry out direct powder compression, make sheet and heavily be the double sodium valproate orally disintegrating tablets of 250mg.
Result of the test:
Tablet hardness: 30 ± 5N
Disintegration: 15～30s
Disintegrate in intraoral disintegration time limit and mouthfeel: the 40S, no grittiness, cool taste does not have uncomfortable taste
Embodiment 3
Double sodium valproate orally disintegrating tablets comprises principal agent and adjuvant, it is characterized in that by following percentage by weight formulated: principal agent 30%, adjuvant 70%.
Divalproex sodium 75g (30%)
Microcrystalline Cellulose 25g (10%)
Mannitol 100g (40%)
Lactose 12.5g (5%)
Polyacrylic resin II 12.5g (5%)
Crospolyvinylpyrrolidone 12.5g (5%)
Cyclamate 2.0g (1%)
Menthol 2.5 (1%)
Micropowder silica gel 7.5 (3%)
Make 1000 altogether
Wherein lactose, mannitol are filler, and microcrystalline Cellulose, crospolyvinylpyrrolidone are disintegrating agent, and polyacrylic resin II, cyclamate and menthol are correctives, and micropowder silica gel is a fluidizer.
The preparation method of divalproex sodium of the present invention comprises raw material pulverizing, weighing mixing, granulation, sheeting process.It is characterized in that concrete processing step is as follows:
Step 1: divalproex sodium is reached and above-mentioned various adjuvant pulverize separately, cross 100 mesh sieves then, preserve standby respectively;
Step 2: take by weighing polyacrylic resin II by recipe quantity, add dehydrated alcohol and make its dissolving in right amount, take by weighing divalproex sodium by above-mentioned recipe quantity and add in this lysate, dry under 50 ℃ of temperature, take out and pulverize, cross 80 mesh sieves, standby;
Step 3: take by weighing residue each component and the abundant mix homogeneously of step 2 component in the prescription by above-mentioned recipe quantity;
Step 4: the component that step 3 mixes is sent into conventional tablet machine, carry out direct powder compression, make sheet and heavily be the double sodium valproate orally disintegrating tablets of 250mg.
Result of the test:
Tablet hardness: 30 ± 5N
Disintegration: 15～30s
Disintegrate in intraoral disintegration time limit and mouthfeel: the 40S, no grittiness, cool taste does not have uncomfortable taste
The double sodium valproate orally disintegrating tablets disintegrate that the present invention relates to is rapid, mouthfeel good, and the no grittiness that enters the mouth and cool taste do not have other uncomfortable taste yet; Can effectively treat epilepsy, mania and prevention migraine, absorb soon the bioavailability height.Take medicine to the patient of old man, children's or dysphagia and the inconvenient person that fetches water convenience is provided.
Claims (1)
1. a double sodium valproate orally disintegrating tablets comprises principal agent and adjuvant, it is characterized in that by following percentage by weight formulated: principal agent 10%-30%, adjuvant 70%-90%; Wherein principal agent is a divalproex sodium; The principal agent divalproex sodium with enteric material polyacrylic resin II parcel, is used further to tabletting earlier; Adjuvant is microcrystalline Cellulose, mannitol, lactose, polyacrylic resin II, crospolyvinylpyrrolidone, cyclamate, menthol, micropowder silica gel; Described adjuvant is formulated by following percentage by weight:
A. microcrystalline Cellulose 10-30%
B. mannitol 10-60%
C. lactose 0-30%
D. polyacrylic resin II 0-15%
E. crospolyvinylpyrrolidone 3-10%
F. cyclamate 1-5%
G. menthol 0.1-1%
H. micropowder silica gel 0.5-3%
Wherein lactose, mannitol are filler, and microcrystalline Cellulose, crospolyvinylpyrrolidone are disintegrating agent, and polyacrylic resin II, cyclamate and menthol are correctives, and micropowder silica gel is a fluidizer;
The preparation method of described double sodium valproate orally disintegrating tablets comprises raw material pulverizing, weighing mixing, granulation, sheeting process, it is characterized in that, concrete processing step is as follows:
Step 1: with divalproex sodium and various adjuvant pulverize separately, cross the 80-100 mesh sieve then, preserve standby respectively;
Step 2: take by weighing polyacrylic resin II by recipe quantity, add dehydrated alcohol and make its dissolving in right amount, take by weighing divalproex sodium by recipe quantity and add in this lysate, dry under the 40-50 ℃ of temperature, take out and pulverize, cross the 80-100 mesh sieve, standby;
Step 3: take by weighing other adjuvant in filler, disintegrating agent and the accessory formula by accessory formula, and with its abundant mix homogeneously;
Step 4: with the granule and the abundant mix homogeneously of the mixed uniformly component of step 3 of step 2;
Step 5: the mixed uniformly component of step 4 is sent into tablet machine, carry out direct powder compression.
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| CN106727386A (en) * | 2017-02-27 | 2017-05-31 | 佛山市弘泰药物研发有限公司 | A kind of divalproex sodium dispersible tablet and preparation method thereof |
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