CN105853379A - Ramelteon dispersible tablet and preparation process thereof - Google Patents
Ramelteon dispersible tablet and preparation process thereof Download PDFInfo
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- CN105853379A CN105853379A CN201610197765.8A CN201610197765A CN105853379A CN 105853379 A CN105853379 A CN 105853379A CN 201610197765 A CN201610197765 A CN 201610197765A CN 105853379 A CN105853379 A CN 105853379A
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- ramelteon
- dispersible tablet
- mannitol
- altogether
- powder
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
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- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
- A61K31/343—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
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- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention belongs to the field of pharmaceutical preparations, and discloses a ramelteon dispersible tablet and a preparation process thereof. The dispersible tablet is prepared through powdering a raw material together with a hydrophilic adjuvant, wherein the hydrophilic adjuvant is composed of mannitol. The material that is powdered together with mannitol is composed of ramelteon. The weight ratio of ramelteon to mannitol is 1: 2 to 1: 10. According to the technical scheme of the invention, the dissolution of ramelteon is effectively improved. Meanwhile, the change of the dissolution behavior of insoluble drugs is effectively inhibited at the same time.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, be specifically related to ramelteon dispersible tablet and preparation technology thereof.
Background technology
Ramelteon (Ramelteon, RozeremTM) is by the oral hypnotic drug of Wu Tian company of Japan research and development, is the
One melatonin receptor agonist being applied to clinical treatment insomnia, has higher affine with melatonin MT1 and MT2 receptor
Power, is the complete agonism of specificity to MT1 and MT2 receptor, and not with MT3 receptor acting.Additionally, it not with GABA receptor etc.
Neurotransmitter receptor combines, and does not the most disturb the activity of most enzyme, accordingly, it is capable to avoid relevant to GABA medicine in certain scope
Distractibility (may result in an automobile accident, fracture etc. of falling) and drug dependence and dependency.Its major metabolite M-II
Total amount is 20-100 times of parent, but activity is relatively low, respectively may be about the 1/5 and 1/ of parent with the affinity of MT1 and MT2 receptor
10.Compared with original shape medicine, its pharmacologically active reduces about 17-25 times.Other metabolite of this product are inactive.Ramelteon is distinguished
In 2005,2010 in the U.S., Japan's listing, be mainly used in treatment and have difficulty in going to sleep type insomnia, to chronic insomnia and short-term
Insomnia also has definite curative effect, uses safety, treats window width, and untoward reaction is few, and long-term prescription does not produce dependence.This product has been soluble in
Machine solvent, is slightly soluble in water and pH3～11 buffer systems.This product has a following structural formula:
。
At present common formulations is tablet, the dissolving feature of ramelteon, makes effective ingredient regardless of whether micronization or add
Add other various binding agents multiple or strengthen adjustment disintegrating agent all dissolutions slowly, the dissolution obvious difference of ramelteon tablet.
The present invention provides the dosage form of a kind of taking convenience, it is to avoid the swallowed whole of tablet.Dispersible tablet disintegration rate is fast,
Put into and water is dispersed into uniform suspension, solve drug-eluting problem slowly.Taking convenience, to there being the old of dysphagia
For year patient, it is beneficial to improve the compliance taken medicine.
Summary of the invention
Present invention aim at providing a kind of ramelteon dispersible tablet, have dispersion speed rapidly, taking convenience, the most instant
Go out, advantage that dissolution difference is little.
Invention provides for ramelteon and hydrophilicity condiment mannitol powder altogether.
The mass ratio that the invention provides ramelteon and mannitol powder altogether is 1:2 ~ 1:10.
The invention provides ramelteon with mannitol powder thing particle diameter altogether less than 40 μm.
The ramelteon dispersible tablet that the present invention provides, described excipient is lactose and mannitol.
The ramelteon dispersible tablet that the present invention provides, described disintegrating agent is polyvinylpolypyrrolidone.
The ramelteon dispersible tablet that the present invention provides, described lubricant is magnesium stearate.
The present invention also provides for the preparation method of described ramelteon dispersible tablet, and specific embodiments is as follows.
(1) by ramelteon and crude drug powder altogether, standby；
(2) by (1) gained powder thing altogether and other auxiliary materials and mixing, 30% alcohol granulation；
(3) (2) being pelletized with 10-24 mesh, dry at 40-55 DEG C, moisture control, below 3%, obtains granule；
(4) by (3) gained granule additional material tabletted.
Beneficial effects of the present invention: the ramelteon tablet result of extraction that the present invention provides is good, and dissolution between batch
Change obtained obvious improvement.
Detailed description of the invention
Embodiment 1:
| Title | Consumption (g) |
| Thunder rice replaces amine | 8 |
| Lactose | 40 |
| Mannitol | 130 |
| Polyvinylpolypyrrolidone | 10 |
| Polyvinylpolypyrrolidone (additional) | 10 |
| Magnesium stearate (additional) | 2 |
| Amount to | 200 |
Note: in form, supplementary material is every 1000 preparation unit consumptions
Preparation technology:
(1) A crossing 100 mesh sieves, B Yu C crosses 80 mesh sieves respectively, A-D crosses 60 mesh sieve mixings, obtains mixture, add 30% ethanol pair
Mixture soft material, 20 mesh sieves are pelletized, and dry temperature and control at 50 DEG C, and pellet moisture controls to less than 30%, granulate, gained
After grain mixes with recipe quantity E and F, on tablet machine, it is pressed into 1000, packs after the assay was approved；
(2) above method repeats three batches (lot number is followed successively by RMT01C01, RMT01C02, RMT01C03)
Embodiment 2:
| Title | Consumption (g) |
| Thunder rice replaces amine (micronized) | 8 |
| Lactose | 40 |
| Mannitol | 130 |
| Polyvinylpolypyrrolidone | 10 |
| Polyvinylpolypyrrolidone (additional) | 10 |
| Magnesium stearate (additional) | 2 |
| Amount to | 200 |
Note: in form, supplementary material is every 1000 preparation unit consumptions
Preparation technology:
(1) by A micronized to 40 μm, B Yu C crosses 80 mesh sieves respectively, A-D crosses 60 mesh sieve mixings, obtains mixture, add 30% second
Alcohol, to granulating mixture, is dried temperature and is controlled at 50 DEG C, and pellet moisture controls to less than 30%, gained granule and recipe quantity E and F
After mixing, on tablet machine, it is pressed into 1000, packs after the assay was approved.
(2) above method repeats three batches (lot number is followed successively by RMT02C01, RMT02C02, RMT02C03).
Embodiment 3:
| Title | Consumption (g) |
| Thunder rice replaces amine (micronized) | 8 |
| Lactose | 40 |
| Mannitol | 130 |
| Polyvinylpolypyrrolidone | 10 |
| Polyvinylpolypyrrolidone (additional) | 10 |
| Magnesium stearate (additional) | 2 |
| Amount to | 200 |
Note: in form, supplementary material is every 1000 preparation unit consumptions
Preparation technology:
(1) by A micronized to 30 μm, B Yu C crosses 80 mesh sieves respectively, A-D crosses 60 mesh sieve mixings, obtains mixture, add 30% second
Alcohol, to granulating mixture, is dried temperature and is controlled at 50 DEG C, and pellet moisture controls to less than 30%, gained granule and recipe quantity E and F
After mixing, on tablet machine, it is pressed into 1000, packs after the assay was approved.
(2) above method repeats three batches (lot number is followed successively by RMT03C01, RMT03C02, RMT03C03).
Embodiment 4:
| Title | Consumption (g) |
| Thunder rice replaces amine (micronized) | 8 |
| Lactose | 40 |
| Mannitol | 130 |
| Polyvinylpolypyrrolidone | 10 |
| Polyvinylpolypyrrolidone (additional) | 10 |
| Magnesium stearate (additional) | 2 |
| Amount to | 200 |
Note: in form, supplementary material is every 1000 preparation unit consumptions
Preparation technology:
(1) by A micronized to 20 μm, B Yu C crosses 80 mesh sieves respectively, A-D crosses 60 mesh sieve mixings, obtains mixture, add 30% second
Alcohol, to granulating mixture, is dried temperature and is controlled at 50 DEG C, and pellet moisture controls to less than 30%, gained granule and recipe quantity E and F
After mixing, on tablet machine, it is pressed into 1000, packs after the assay was approved.
(2) above method repeats three batches (lot number is followed successively by RMT04C01, RMT04C02, RMT04C03).
Embodiment 5:
| Title | Consumption (g) |
| Thunder rice is for amine and mannitol powder thing (1:10) altogether | 88 |
| Lactose | 40 |
| Mannitol | 50 |
| Polyvinylpolypyrrolidone | 10 |
| Polyvinylpolypyrrolidone (additional) | 10 |
| Magnesium stearate (additional) | 2 |
| Amount to | 200 |
Note: in form, supplementary material is every 1000 preparation unit consumptions
Preparation technology:
(1) by A micronized to 40 μm, B Yu C crosses 80 mesh sieves respectively, A-D crosses 60 mesh sieve mixings, obtains mixture, add 30% second
Alcohol, to granulating mixture, is dried temperature and is controlled at 50 DEG C, and pellet moisture controls to less than 30%, gained granule and recipe quantity E and F
After mixing, on tablet machine, it is pressed into 1000, packs after the assay was approved.
(2) above method repeats three batches (lot number is followed successively by RMT05C01, RMT05C02, RMT05C03).
Embodiment 6:
| Title | Consumption (g) |
| Thunder rice is for amine and mannitol powder thing (1:10) altogether | 88 |
| Lactose | 40 |
| Mannitol | 50 |
| Polyvinylpolypyrrolidone | 10 |
| Polyvinylpolypyrrolidone (additional) | 10 |
| Magnesium stearate (additional) | 2 |
| Amount to | 200 |
Note: in form, supplementary material is every 1000 preparation unit consumptions
Preparation technology:
(1) by A micronized to 30 μm, B Yu C crosses 80 mesh sieves respectively, A-D crosses 60 mesh sieve mixings, obtains mixture, add 30% second
Alcohol, to granulating mixture, is dried temperature and is controlled at 50 DEG C, and pellet moisture controls to less than 30%, gained granule and recipe quantity E and F
After mixing, on tablet machine, it is pressed into 1000, packs after the assay was approved；
(2) above method repeats three batches (lot number is followed successively by RMT06C01, RMT06C02, RMT06C03).
Embodiment 7:
| Title | Consumption (g) |
| Thunder rice is for amine and mannitol powder thing (1:10) altogether | 88 |
| Lactose | 40 |
| Mannitol | 50 |
| Polyvinylpolypyrrolidone | 10 |
| Polyvinylpolypyrrolidone (additional) | 10 |
| Magnesium stearate (additional) | 2 |
| Amount to | 200 |
Note: in form, supplementary material is every 1000 preparation unit consumptions.
Preparation technology:
(1) by A micronized to 20 μm, B Yu C crosses 80 mesh sieves respectively, A-D crosses 60 mesh sieve mixings, obtains mixture, add 30% second
Alcohol, to granulating mixture, is dried temperature and is controlled at 50 DEG C, and pellet moisture controls to less than 30%, gained granule and recipe quantity E and F
After mixing, on tablet machine, it is pressed into 1000, packs after the assay was approved；
(2) above method repeats three batches (lot number is followed successively by RMT07C01, RMT07C02, RMT07C03).
Ramelteon stripping curve contrasts
| Dissolution (%) | Embodiment 1 | Embodiment 2 | Embodiment 3 | Embodiment 4 | Embodiment 5 | Embodiment 6 | Embodiment 7 | Commercially available control formulation |
| 5min | 29.33 | 32.11 | 33.24 | 32.96 | 69.52 | 45.62 | 51.23 | 27.62 |
| 15min | 38.56 | 41.35 | 42.22 | 43.29 | 90.22 | 93.94 | 97.65 | 32.55 |
| 30min | 45.63 | 49.35 | 48.62 | 49.85 | 99.54 | 100.32 | 99.15 | 45.43 |
| 45min | 57.52 | 58.12 | 60.84 | 61.52 | 99.23 | 99.84 | 99.13 | 58.54 |
| 60min | 62.31 | 65.56 | 64.96 | 65.21 | 100.25 | 99.32 | 99.85 | 72.46 |
Result shows, the dissolution of medicine is total to mannitol by the independent micronized of crude drug without impact, the crude drug that the present invention obtains
It is good that powder thing prepares ramelteon dispersible tablet result of extraction, and significance adds the dissolution of medicine.
The similar factors of table 1. embodiment 1 three batch sample
| The similar factors of embodiment 1 | |
| RMT01C01 and RMT01C02 | 44 |
| RMT01C01 and RMT01C03 | 25 |
| RMT01C02 and RMT01C03 | 31 |
The similar factors of table 2. embodiment 2 three batch sample
| The similar factors of embodiment 2 | |
| RMT02C01 and RMT02C02 | 42 |
| RMT02C01 and RMT02C03 | 35 |
| RMT02C02 and RMT02C03 | 46 |
The similar factors of table 3. embodiment 3 three batch sample
| The similar factors of embodiment 3 | |
| RMT03C01 and RMT03C02 | 34 |
| RMT03C01 and RMT03C03 | 26 |
| RMT03C02 and RMT03C03 | 42 |
The similar factors of table 4. embodiment 4 three batch sample
| The similar factors of embodiment 4 | |
| RMT04C01 and RMT04C02 | 36 |
| RMT04C01 and RMT04C03 | 26 |
| RMT04C02 and RMT04C03 | 34 |
The similar factors of table 5. embodiment 5 three batch sample
| The similar factors of embodiment 5 | |
| RMT01C01 and RMT01C02 | 85 |
| RMT01C01 and RMT01C03 | 94 |
| RMT01C02 and RMT01C03 | 89 |
The similar factors of table 6. embodiment 6 three batch sample
| The similar factors of embodiment 6 | |
| RMT06C01 and RMT06C02 | 91 |
| RMT06C01 and RMT06C03 | 90 |
| RMT06C02 and RMT06C03 | 89 |
The similar factors of table 7. embodiment 7 three batch sample
| The similar factors of embodiment 1 | |
| RMT01C01 and RMT01C02 | 91 |
| RMT01C01 and RMT01C03 | 95 |
| RMT01C02 and RMT01C03 | 90 |
Result shows that the ramelteon dispersible tablet tablet result of extraction that the present invention obtains is good, and the dissolution change between batch is little.
Claims (10)
1. a ramelteon dispersible tablet, it is characterised in that by ramelteon and hydrophilicity condiment powder altogether, and use wet granulation
Tablet forming technique.
Ramelteon dispersible tablet the most according to claim 1, it is characterised in that hydrophilicity condiment used is mannitol.
Ramelteon dispersible tablet the most according to claim 1, it is characterised in that ramelteon and mannitol powder consumption altogether is pressed
Weight ratio 1:2 ~ 1:10.
Ramelteon dispersible tablet the most according to claim 1, it is characterised in that ramelteon and the common powder footpath of mannitol
It is not more than 40 μm.
Ramelteon dispersible tablet the most according to claim 4, powder thing mean diameter is 10 ~ 30 μm altogether.
Dispersible tablet the most according to claim 4, it is characterised in that it is possibly together with excipient, disintegrating agent and lubricant.
Dispersible tablet the most according to claim 6, it is characterised in that described excipient is selected from lactose, mannitol and microcrystalline cellulose
Element one or both.
Dispersible tablet the most according to claim 6, it is characterised in that described disintegrating agent is selected from polyvinylpolypyrrolidone, cross-linked carboxymethyl
Sodium cellulosate, polacrilin potassium one or both.
Dispersible tablet the most according to claim 6, it is characterised in that described lubricant is selected from sodium stearyl fumarate, stearic acid
Magnesium, Pulvis Talci one or both.
10. the preparation method of the arbitrary described ramelteon dispersible tablet of claim 1 to 9, including:
(1) by ramelteon and mannitol powder altogether；
(2) by (1) gained powder thing altogether and other auxiliary materials and mixing, 30% alcohol granulation；
(3) (2) being pelletized with 10-24 mesh, dry at 40-55 DEG C, moisture control, below 3%, obtains granule；
(4) by (3) gained granule additional material tabletted.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610197765.8A CN105853379A (en) | 2016-03-31 | 2016-03-31 | Ramelteon dispersible tablet and preparation process thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610197765.8A CN105853379A (en) | 2016-03-31 | 2016-03-31 | Ramelteon dispersible tablet and preparation process thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105853379A true CN105853379A (en) | 2016-08-17 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610197765.8A Pending CN105853379A (en) | 2016-03-31 | 2016-03-31 | Ramelteon dispersible tablet and preparation process thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105853379A (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103429223A (en) * | 2011-01-17 | 2013-12-04 | 武田药品工业株式会社 | Orally dispersible tablet |
| CN104546770A (en) * | 2015-01-07 | 2015-04-29 | 万特制药(海南)有限公司 | Azilsartan orally-disintegrating tablet and preparation method thereof |
-
2016
- 2016-03-31 CN CN201610197765.8A patent/CN105853379A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103429223A (en) * | 2011-01-17 | 2013-12-04 | 武田药品工业株式会社 | Orally dispersible tablet |
| CN104546770A (en) * | 2015-01-07 | 2015-04-29 | 万特制药(海南)有限公司 | Azilsartan orally-disintegrating tablet and preparation method thereof |
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Application publication date: 20160817 |