CN105816441A - Memantine hydrochloride and donepezil hydrochloride composite preparation - Google Patents
Memantine hydrochloride and donepezil hydrochloride composite preparation Download PDFInfo
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- CN105816441A CN105816441A CN201610370100.2A CN201610370100A CN105816441A CN 105816441 A CN105816441 A CN 105816441A CN 201610370100 A CN201610370100 A CN 201610370100A CN 105816441 A CN105816441 A CN 105816441A
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- memantine
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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
- A61K31/13—Amines
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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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
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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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
- A61K9/5042—Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
- A61K9/5047—Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose
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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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5073—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings
- A61K9/5078—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings with drug-free core
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Abstract
The invention discloses a memantine hydrochloride and donepezil hydrochloride composite preparation .Memantine hydrochloride and donepezil hydrochloride serve as medicine active components and wrap a pellet together, the slow release of memantine hydrochloride and the rapid release of donepezil hydrochloride are controlled in a multi-layer coating mode, finally the preparation is filled in a capsule, the problem that the capsule filled with the pellet and the particle mixture is possibly not uniform in filling is solved, industrial production is easy, no lactose or other auxiliaries which can have a Maillard reaction with memantine hydrochloride exist, the stability of the preparation is ensured.
Description
Technical field
The present invention relates to pharmaceutical preparation, be specifically related to memantine donepezil compound preparation, especially with memantine slow-release micro-pill and the capsule of donepezil hydrochloride fast release micropill.
Background technology
Memantine donepezil compound preparation is used to treat the medicine suffering from moderate to severe alzheimer's disease forms of dementia patient.Recommended dose is 28mg memantine/10mg donepezil hydrochloride/sky, or 10mg memantine/10mg donepezil hydrochloride/sky, for severe renal functional lesion patient, recommended dose is 14mg memantine slow release/10mg donepezil hydrochloride, or 5mg memantine/10mg donepezil hydrochloride, once a day.
Memantine-donepezil hydrochloride capsule is by Arstwyth and Adamas drugmaker joint development, and in December, 2014 in FDA approval listing, dosage form is capsule, specification is memantine 14mg/ donepezil hydrochloride 10mg and memantine 28mg/ donepezil hydrochloride 10mg, trade name:Chemical name is 3, and 5-dimethyl amantadine hydrochloride and (2RS)-2-[(1-benzyl pyridine-4-base) methyl]-5,6-dimethoxy-2,3-dihydro-1H-indone-1-hydrochlorate, molecular formula is respectively as follows: C12H21N HCl and C24H29NO3HCl, molecular weight is respectively as follows: 215.76 and 415.96, and its structure is as follows:
Memantine is white or off-white color fine powder, dissolves in water, by the speed of release membranes technological adjustment principal agent dissolution in preparation, thus controls its internal absorption；
Donepezil hydrochloride is white or crystalline powder, dissolves, reach the purpose quickly discharged in preparation by the way of separately made instant granular in water.
Prior art patent WO-2005072705 discloses the compound preparation of a kind of memantine and donepezil hydrochloride, and wherein memantine is slow-release micro-pill, and donepezil hydrochloride is immediate-release granules, and common fill is in capsule.This kind of process industryization is amplified more difficult, requires higher to capsule filling apparatus, and a lot of workshops do not reach requirement.And mentioning in patent that donepezil uses lactose to carry out donepezil granule as adjuvant and prepares, lactose is susceptible to Maillard reaction for memantine, generates lactose adduct, is unfavorable for the stability of preparation.
Summary of the invention
The present invention proposes a kind of memantine donepezil compound preparation, to improve the stability of preparation and to realize industrialization amplification；
The present invention proposes a kind of memantine donepezil compound preparation, relates to slow releasing capsule and preparation method thereof；
The present invention proposes a kind of memantine donepezil compound preparation, it is characterised in that its composition is as follows:
The present invention proposes a kind of memantine donepezil compound preparation, it is characterised in that its weight portion composition is as follows:
A kind of memantine donepezil compound preparation, it is characterised in that preparation method comprises the steps:
Take memantine, and a part of polyvidone dissolve with suitable solvent, stir to after being completely dissolved, be uniformly wrapped on fine pellet core,
Aquacoat is uniformly wrapped on the fine pellet core of hydrochloric memantine, after a part of Opadry is dissolved with suitable solvent after, wrap up sealing coat,
By donepezil hydrochloride, and a part of polyvidone dissolves with suitable solvent, stirs to after being completely dissolved, is wrapped on above-mentioned fine pellet core,
After being dissolved with suitable solvent by a part of Opadry, wrap up sealing coat.
A kind of memantine donepezil compound preparation, it is characterised in that: slow releasing capsule, two kinds of ingredients are wrapped in the different coatings of micropill, respectively with different rate of releasing drug release medicines；
Described slow release layer is any one or more in hypromellose, methylcellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxypropylcellulose, hydroxypropyl methyl cellulose, carboxymethyl cellulose, polyvinylpyrrolidone, polyacrylic resin；
Described fine pellet core be microcrystalline Cellulose, starch, pregelatinized Starch, in any one or more；
Described binding agent is any one or more in polyvidone, xanthan gum, hypromellose, carboxymethyl cellulose；
Preparation method comprises the steps:
Take memantine, and a part of polyvidone dissolve with suitable solvent, stir to after being completely dissolved, use the mode of spray or centrifugal granulator side spray at the bottom of fluid bed to be uniformly wrapped on fine pellet core,
Aquacoat is uniformly wrapped on the fine pellet core of hydrochloric memantine, after a part of Opadry is dissolved with suitable solvent after, use the mode of spray or centrifugal granulator side spray at the bottom of fluid bed to wrap up sealing coat,
Again by donepezil hydrochloride, and a part of polyvidone dissolves with suitable solvent, stirs to after being completely dissolved, uses the mode of spray or centrifugal granulator side spray at the bottom of fluid bed to be uniformly wrapped on above-mentioned fine pellet core,
After a part of Opadry is dissolved with suitable solvent after, use the mode of spray or centrifugal granulator side spray at the bottom of fluid bed to wrap up sealing coat,
Afterwards according to the result fill of assay in Capsules shell, i.e. obtain a kind of containing slow release and the capsule of immediate release drug micropill.
Described solvent is ethanol, purified water or both mixed solutions.
Described slow release and rapid release situation, it is characterised in that slow-released part memantine slowly discharged in 16 hours, immediate release section donepezil hydrochloride discharges in 30 minutes completely.
A kind of memantine donepezil compound preparation, it is characterised in that: preparation method, it is characterised in that packaging medicine, sustained release film and isolated material device therefor are bottom spraying type fluid bed or centrifugal granulator.
Memantine is wrapped in the coatings of micropill, it is preferred to use polyvidone is binding agent, and dimension ketone has good water solublity, and when water penetrates into main medicament layer by slow release layer when, polyvidone can dissolve and drive medicine to discharge；
Donepezil hydrochloride is wrapped in the coatings of micropill, it is preferred to use polyvidone is binding agent；
Film controlled-release material preferably employs ethyl cellulose, and its slow release effect can be regulated by the thickness of ethyl cellulose, by finally determining the consumption of ethyl cellulose with former triturate contrast stripping curve；
Discharged medicine by the scattering and permeating of ethyl cellulose, the weight fraction of the ethoxy group of ethyl cellulose is suitably 25%-75%, preferably 40%-60%, preferably 45%；
Film controlled-release material preferably employs ethyl cellulose, span, the mixture of oil；
Film controlled-release material preferably employs ethyl cellulose, span, oil, the mixture of lightweight silica gel；
When dissolving memantine, donepezil hydrochloride, it is preferred to use 30-60% alcohol solvent,
When dissolving memantine, donepezil hydrochloride, it is preferred to use 50% alcohol solvent, the reason using 50% alcohol solvent is two aspects, and raw material is easier to dissolve wherein, is easier to be dried during fluidized bed coating.
The present invention has the advantage that with good effect:
Can be with the adjuvant of memantine generation Maillard reaction without xylitol, arabinose, lactose, mannitol, glucitol etc. in prescription, it is ensured that the stability of preparation release.
The present invention by being wrapped in the different coatings of micropill respectively by memantine and two kinds of medicines of donepezil hydrochloride; achieve memantine and slowly discharge the quick release with donepezil hydrochloride; it is wrapped on micropill simultaneously; thus avoid micropill and the uneven problem of capsule filling that may be present is filled in granule mixing; and easily realize industrialized production, it is to avoid particular/special requirement to equipment in technique.
Accompanying drawing explanation
Fig. 1 illustrates the accumulation Dissolution profiles of external 1 hour of donepezil hydrochloride in the memantine-donepezil hydrochloride capsule of the embodiment 1 in the present invention.
Fig. 2 illustrates the Accumulation dissolution curve of external 12 hours of memantine in the memantine-donepezil hydrochloride capsule of the embodiment 1 in the present invention.
Fig. 3 illustrates the effect structure of the memantine of embodiment 1 in the present invention-donepezil hydrochloride multilamellar micropill.
Detailed description of the invention
Below in conjunction with specific embodiment, the invention will be further described, but does not limit protection scope of the present invention.
Embodiment 1
A kind of memantine donepezil compound preparation, formulated by following component,
Memantine 14.0g
Donepezil hydrochloride 10.0g
Microcrystalline cellulose pellets capsule core 70.0g
Aquacoat 24.0g
Polyvidone 6.0g
Opadry 3.3g
Its preparation method comprises the steps:
1) memantine and polyvidone (3.0g) use 50% alcohol solvent to dissolve, and are wrapped in microcrystalline cellulose pellets capsule core surface,
2) Aquacoat is used to carry out the coating of slow release layer,
3) Opadry (1.3g) is added water it is configured to the aqueous solution of 8% concentration, be wrapped in micropill surface as sealing coat 1,
4) donepezil hydrochloride and polyvidone (3.0g) use the solvent of 50% ethanol to dissolve, and are wrapped in next layer of microcrystalline cellulose pellets capsule core, as rapid delivery of pharmaceuticals layer,
5) Opadry (2.0g) is added water it is configured to the aqueous solution of 8% concentration, be wrapped in micropill outermost layer as sealing coat 2.
6) medicament contg is measured, the theoretical loading amount of conversion, complete capsule fill.
Result of the test
Medicament contg: qualified
Disintegration: meet regulation
Donepezil hydrochloride 15min dissolution: 94.23%
Memantine slowly discharges, 3 hours dissolutions 31%, 5 hours dissolutions 56%, 8 hours dissolutions 82%.
The accumulation Dissolution profiles of external 1 hour of donepezil hydrochloride in the memantine of the embodiment 1 in the present invention-donepezil hydrochloride capsule, under equal conditions, the ratio accumulation Dissolution profiles excellence 15% of prior art, stability to improve 8%.
Embodiment 2
A kind of memantine donepezil compound preparation, formulated by following component,
Memantine 14.0g
Donepezil hydrochloride 10.0g
Microcrystalline cellulose pellets capsule core 62.0g
Aquacoat 32.0g
Polyvidone 6.0g
Opadry 3.3g
Its preparation method comprises the steps:
1) memantine and polyvidone (3.0g) use 50% alcohol solvent to dissolve, and are wrapped in microcrystalline cellulose pellets capsule core surface,
2) Aquacoat is used to carry out the coating of slow release layer,
3) Opadry (1.3g) is added water it is configured to the aqueous solution of 8% concentration, be wrapped in micropill surface as sealing coat 1,
4) donepezil hydrochloride and polyvidone (3.0g) use the solvent of 50% ethanol to dissolve, and are wrapped in next layer of microcrystalline cellulose pellets capsule core, as rapid delivery of pharmaceuticals layer,
5) Opadry (2.0g) is added water it is configured to the aqueous solution of 8% concentration, be wrapped in micropill outermost layer as sealing coat 2.
6) medicament contg is measured, the theoretical loading amount of conversion, complete capsule fill.
Result of the test
Medicament contg: qualified
Disintegration: meet regulation
Donepezil hydrochloride 15min dissolution: 93.46%
Memantine slowly discharges, 3 hours dissolutions 18%, 5 hours dissolutions 46%, 8 hours dissolutions 60%.
Embodiment 3
A kind of memantine donepezil compound preparation, formulated by following component,
Memantine 14.0g
Donepezil hydrochloride 10.0g
Microcrystalline cellulose pellets capsule core 66.0g
Aquacoat 28.0g
Polyvidone 6.0g
Opadry 3.3g
Its preparation method comprises the steps:
1) memantine and polyvidone (3.0g) use 50% alcohol solvent to dissolve, and are wrapped in microcrystalline cellulose pellets capsule core surface,
2) Aquacoat is used to carry out the coating of slow release layer,
3) Opadry (1.3g) is added water it is configured to the aqueous solution of 8% concentration, be wrapped in micropill surface as sealing coat 1,
4) donepezil hydrochloride and polyvidone (3.0g) use the solvent of 50% ethanol to dissolve, and are wrapped in next layer of microcrystalline cellulose pellets capsule core, as rapid delivery of pharmaceuticals layer,
5) Opadry (2.0g) is added water it is configured to the aqueous solution of 8% concentration, be wrapped in micropill outermost layer as sealing coat 2.
6) medicament contg is measured, the theoretical loading amount of conversion, complete capsule fill.
Result of the test
Medicament contg: qualified
Disintegration: meet regulation
Donepezil hydrochloride 15min dissolution: 92.17%
Memantine slowly discharges, 3 hours dissolutions 26%, 5 hours dissolutions 50%, 8 hours dissolutions 71%.
Detection method uses in USP and mentions Memantine hydrochloride tablet and donepezil preparation correlation method.
Embodiment 4
A kind of memantine donepezil compound preparation, formulated by following component,
Memantine 14.0g
Donepezil hydrochloride 10.0g
Microcrystalline cellulose pellets capsule core 66.0g
Aquacoat 24.0g
Polyvidone 10.0g
Opadry 3.3g
Its preparation method comprises the steps:
1) memantine and polyvidone (5.0g) use 50% alcohol solvent to dissolve, and are wrapped in microcrystalline cellulose pellets capsule core surface,
2) Aquacoat is used to carry out the coating of slow release layer,
3) Opadry (1.3g) is added water it is configured to the aqueous solution of 8% concentration, be wrapped in micropill surface as sealing coat 1,
4) donepezil hydrochloride and polyvidone (5.0g) use the solvent of 50% ethanol to dissolve, and are wrapped in next layer of microcrystalline cellulose pellets capsule core, as rapid delivery of pharmaceuticals layer,
5) Opadry (2.0g) is added water it is configured to the aqueous solution of 8% concentration, be wrapped in micropill outermost layer as sealing coat 2.
6) medicament contg is measured, the theoretical loading amount of conversion, complete capsule fill.
Result of the test
Medicament contg: qualified
Disintegration: meet regulation
Donepezil hydrochloride 15min dissolution: 90.36%
Memantine slowly discharges, 3 hours dissolutions 29%, 5 hours dissolutions 55%, 8 hours dissolutions 76%.
Embodiment 5
A kind of memantine donepezil compound preparation, formulated by following component,
Memantine 14.0g
Donepezil hydrochloride 10.0g
Microcrystalline cellulose pellets capsule core 58.0g
Aquacoat 24.0g
Polyvidone 18.0g
Opadry 3.3g
Its preparation method comprises the steps:
1) memantine and polyvidone (9.0g) use 50% alcohol solvent to dissolve, and are wrapped in microcrystalline cellulose pellets capsule core surface,
2) Aquacoat is used to carry out the coating of slow release layer,
3) Opadry (1.3g) is added water it is configured to the aqueous solution of 8% concentration, be wrapped in micropill surface as sealing coat 1,
4) donepezil hydrochloride and polyvidone (9.0g) use the solvent of 50% ethanol to dissolve, and are wrapped in next layer of microcrystalline cellulose pellets capsule core, as rapid delivery of pharmaceuticals layer,
5) Opadry (2.0g) is added water it is configured to the aqueous solution of 8% concentration, be wrapped in micropill outermost layer as sealing coat 2.
6) medicament contg is measured, the theoretical loading amount of conversion, complete capsule fill.Result of the test
Medicament contg: qualified
Disintegration: meet regulation
Donepezil hydrochloride 15min dissolution: 91.22%
Memantine slowly discharges, 3 hours dissolutions 18%, 5 hours dissolutions 41%, 8 hours dissolutions 65%.
Detection method uses in USP and mentions Memantine hydrochloride tablet and donepezil preparation correlation method.
Embodiment 6
A kind of memantine donepezil compound preparation, formulated by following component,
Memantine 14.0g
Donepezil hydrochloride 10.0g
Microcrystalline cellulose pellets capsule core 62.0g
Aquacoat 24.0g
Polyvidone 16.0g
Opadry 3.3g
Its preparation method comprises the steps:
1) memantine and polyvidone (8.0g) use 50% alcohol solvent to dissolve, and are wrapped in microcrystalline cellulose pellets capsule core surface,
2) Aquacoat is used to carry out the coating of slow release layer,
3) Opadry (1.3g) is added water it is configured to the aqueous solution of 8% concentration, be wrapped in micropill surface as sealing coat 1,
4) donepezil hydrochloride and polyvidone (8.0g) use the solvent of 50% ethanol to dissolve, and are wrapped in next layer of microcrystalline cellulose pellets capsule core, as rapid delivery of pharmaceuticals layer,
5) Opadry (2.0g) is added water it is configured to the aqueous solution of 8% concentration, be wrapped in micropill outermost layer as sealing coat 2.
6) medicament contg is measured, the theoretical loading amount of conversion, complete capsule fill.Result of the test
Medicament contg: qualified
Disintegration: meet regulation
Donepezil hydrochloride 15min dissolution: 94.22%
Memantine slowly discharges, 3 hours dissolutions 33%, 5 hours dissolutions 62%, 8 hours dissolutions 84%.
Embodiment 7
A kind of memantine donepezil compound preparation, formulated by following component,
Memantine 14.0g
Donepezil hydrochloride 10.0g
Microcrystalline cellulose pellets capsule core 62.0g
Aquacoat 24.0g
Sorbester p18 1.0g
Soybean oil 2.0g
Lightweight silica gel 0.5g
Polyvidone 16.0g
Opadry 3.3g
Its preparation method comprises the steps:
1) memantine and polyvidone (8.0g), sorbitan monostearate, soybean oil, the mixing of lightweight silica gel, use 50% alcohol solvent to dissolve, be wrapped in microcrystalline cellulose pellets capsule core surface,
2) Aquacoat is used to carry out the coating of slow release layer,
3) Opadry (1.3g) is added water it is configured to the aqueous solution of 8% concentration, be wrapped in micropill surface as sealing coat 1,
4) donepezil hydrochloride and polyvidone (8.0g) use the solvent of 50% ethanol to dissolve, and are wrapped in next layer of microcrystalline cellulose pellets capsule core, as rapid delivery of pharmaceuticals layer,
5) Opadry (2.0g) is added water it is configured to the aqueous solution of 8% concentration, be wrapped in micropill outermost layer as sealing coat 2.
6) medicament contg is measured, the theoretical loading amount of conversion, complete capsule fill.Result of the test
Medicament contg: qualified
Disintegration: meet regulation
Donepezil hydrochloride 15min dissolution: 93.81%
Memantine slowly discharges, 3 hours dissolutions 36%, 5 hours dissolutions 71%, 8 hours dissolutions 89%.
Embodiment 8
A kind of memantine donepezil compound preparation, formulated by following component,
Memantine 14.0g
Donepezil hydrochloride 10.0g
Microcrystalline cellulose pellets capsule core 62.0g
Aquacoat 24.0g
Sorbester p18 1.0g
Soybean oil 2.0g
Polyvidone 16.0g
Opadry 3.3g
Its preparation method comprises the steps:
1) memantine and polyvidone (8.0g), sorbitan monostearate, soybean oil mixing, use 50% alcohol solvent to dissolve, be wrapped in microcrystalline cellulose pellets capsule core surface,
2) Aquacoat is used to carry out the coating of slow release layer,
3) Opadry (1.3g) is added water it is configured to the aqueous solution of 8% concentration, be wrapped in micropill surface as sealing coat 1,
4) donepezil hydrochloride and polyvidone (8.0g) use the solvent of 50% ethanol to dissolve, and are wrapped in next layer of microcrystalline cellulose pellets capsule core, as rapid delivery of pharmaceuticals layer,
5) Opadry (2.0g) is added water it is configured to the aqueous solution of 8% concentration, be wrapped in micropill outermost layer as sealing coat 2.
6) medicament contg is measured, the theoretical loading amount of conversion, complete capsule fill.Result of the test
Medicament contg: qualified
Disintegration: meet regulation
Donepezil hydrochloride 15min dissolution: 93.68%
Memantine slowly discharges, 3 hours dissolutions 39%, 5 hours dissolutions 76%, 8 hours dissolutions 92%.
Dissolving-out method uses in FDAdissolutionmethods and mentions memantine donepezil compound capsule method
Detection method uses in USP and mentions Memantine hydrochloride tablet and donepezil preparation correlation method.
Embodiment 9
A kind of memantine donepezil compound preparation, formulated by following component,
Memantine 14.0g
Donepezil hydrochloride 10.0g
Lactose fine pellet core 62.0g
Aquacoat 24.0g
Polyvidone 16.0g
Opadry 3.3g
Its preparation method comprises the steps:
1) memantine and polyvidone (8.0g) mixing, use 50% alcohol solvent to dissolve, be wrapped in lactose fine pellet core surface,
2) Aquacoat is used to carry out the coating of slow release layer,
3) Opadry (1.3g) is added water it is configured to the aqueous solution of 8% concentration, be wrapped in micropill surface as sealing coat 1,
4) donepezil hydrochloride and polyvidone (8.0g) use the solvent of 50% ethanol to dissolve, and are wrapped in micropill surface, as rapid delivery of pharmaceuticals layer,
5) Opadry (2.0g) is added water it is configured to the aqueous solution of 8% concentration, be wrapped in micropill outermost layer as sealing coat 2.
6) medicament contg is measured, the theoretical loading amount of conversion, complete capsule fill.Result of the test
Medicament contg: qualified
Disintegration: meet regulation
Donepezil hydrochloride 15min dissolution: 92.53%
Memantine slowly discharges, 3 hours dissolutions 17%, 5 hours dissolutions 42%, 8 hours dissolutions 58%.
Embodiment 10
A kind of memantine donepezil compound preparation, formulated by following component,
Memantine 14.0g
Donepezil hydrochloride 10.0g
Sucrose fine pellet core 62.0g
Aquacoat 24.0g
Polyvidone 16.0g
Opadry 3.3g
Its preparation method comprises the steps:
1) memantine and polyvidone (8.0g) mixing, use 50% alcohol solvent to dissolve, be wrapped in sucrose fine pellet core surface,
2) Aquacoat is used to carry out the coating of slow release layer,
3) Opadry (1.3g) is added water it is configured to the aqueous solution of 8% concentration, be wrapped in micropill surface as sealing coat 1,
4) donepezil hydrochloride and polyvidone (8.0g) use the solvent of 50% ethanol to dissolve, and are wrapped in micropill surface, as rapid delivery of pharmaceuticals layer,
5) Opadry (2.0g) is added water it is configured to the aqueous solution of 8% concentration, be wrapped in micropill outermost layer as sealing coat 2.
6) medicament contg is measured, the theoretical loading amount of conversion, complete capsule fill.Result of the test
Medicament contg: qualified
Disintegration: meet regulation
Donepezil hydrochloride 15min dissolution: 90.18%
Memantine slowly discharges, 3 hours dissolutions 19%, 5 hours dissolutions 36%, 8 hours dissolutions 49%.
Embodiment 11
The selection course of preparation process
A kind of memantine donepezil compound preparation, formulated by following component,
Memantine 14.0g
Donepezil hydrochloride 10.0g
Fine pellet core 62.0g
Aquacoat 24.0g
Polyvidone 16.0g
Opadry 3.3g
Its preparation method comprises the steps:
1) memantine and polyvidone (9.0g) use 30,40,50 or, 60% alcohol solvent dissolve, be wrapped in microcrystalline cellulose pellets capsule core or, lactose fine pellet core surface,
2) Aquacoat is used to carry out the coating of slow release layer,
3) Opadry (1.3g) is added water be configured to 4%, 6%, 8% or, the aqueous solution of 10% concentration, be wrapped in micropill surface as sealing coat 1,
4) donepezil hydrochloride and polyvidone (9.0g) use 30%, 40%, 50% or, the solvent of 60%% ethanol dissolve, be wrapped in next layer of microcrystalline cellulose pellets capsule core, as rapid delivery of pharmaceuticals layer,
5) Opadry (2.0g) is added water be configured to 4%, 6%, 8% or, the aqueous solution of 10% concentration, be wrapped in micropill outermost layer as sealing coat 2.
6) medicament contg is measured, the theoretical loading amount of conversion, complete capsule fill.
Tasting capsule 's content, its mouthfeel taste is as follows:
| Alcohol solvent | Aqueous solution | Fine pellet core | Taste |
| 30% | 4% | Microcrystalline Cellulose | There is abnormal flavour |
| 30% | 6% | Lactose | There is abnormal flavour |
| 30% | 8% | Microcrystalline Cellulose | Free from extraneous odour |
| 30% | 10% | Lactose | There is abnormal flavour |
| 40% | 4% | Microcrystalline Cellulose | There is abnormal flavour |
| 40% | 6% | Lactose | There is abnormal flavour |
| 40% | 8% | Microcrystalline Cellulose | Free from extraneous odour |
| 40% | 10% | Lactose | There is abnormal flavour |
| 50% | 4% | Microcrystalline Cellulose | Free from extraneous odour |
| 50% | 6% | Lactose | Free from extraneous odour 10--> |
| 50% | 8% | Microcrystalline Cellulose | Free from extraneous odour |
| 50% | 10% | Lactose | There is abnormal flavour |
| 60% | 4% | Microcrystalline Cellulose | Free from extraneous odour |
| 60% | 6% | Lactose | There is abnormal flavour |
| 60% | 8% | Microcrystalline Cellulose | Free from extraneous odour |
| 60% | 10% | Lactose | There is abnormal flavour |
Claims (3)
1. a memantine donepezil compound preparation, it is characterised in that its composition is as follows:
2. a memantine donepezil compound preparation, it is characterised in that its weight portion composition is as follows:
3. according to a kind of memantine donepezil compound preparation of claim 1-2, it is characterised in that
Preparation method comprises the steps:
Take memantine, and a part of polyvidone dissolve with suitable solvent, stir to after being completely dissolved, be uniformly wrapped on fine pellet core,
Ethylcellulose mixed suspension liquid is uniformly wrapped on the fine pellet core of hydrochloric memantine, after a part of Opadry is dissolved with suitable solvent after, wrap up sealing coat,
By donepezil hydrochloride, and a part of polyvidone dissolves with suitable solvent, stirs to after being completely dissolved, is wrapped on above-mentioned fine pellet core,
After being dissolved with suitable solvent by a part of Opadry, wrap up sealing coat.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610370100.2A CN105816441A (en) | 2016-05-31 | 2016-05-31 | Memantine hydrochloride and donepezil hydrochloride composite preparation |
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| CN201610370100.2A CN105816441A (en) | 2016-05-31 | 2016-05-31 | Memantine hydrochloride and donepezil hydrochloride composite preparation |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106581682A (en) * | 2016-12-09 | 2017-04-26 | 河南中帅医药科技股份有限公司 | Memantine hydrochloride/donepezil slow-release resin composition and preparation method thereof |
| CN107773553A (en) * | 2016-08-26 | 2018-03-09 | 江苏先声药业有限公司 | A kind of memantine sustained release pellet and preparation method thereof |
| WO2021234475A1 (en) * | 2020-05-21 | 2021-11-25 | Pellets Pharma Limited | Modified release compositions and methods of memantine hcl extended release, donepezil hcl immediate release pellets |
-
2016
- 2016-05-31 CN CN201610370100.2A patent/CN105816441A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107773553A (en) * | 2016-08-26 | 2018-03-09 | 江苏先声药业有限公司 | A kind of memantine sustained release pellet and preparation method thereof |
| CN106581682A (en) * | 2016-12-09 | 2017-04-26 | 河南中帅医药科技股份有限公司 | Memantine hydrochloride/donepezil slow-release resin composition and preparation method thereof |
| WO2021234475A1 (en) * | 2020-05-21 | 2021-11-25 | Pellets Pharma Limited | Modified release compositions and methods of memantine hcl extended release, donepezil hcl immediate release pellets |
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