CN107693502A - 9-hydroxy-risperidone increment type release osmotic pump tablet and preparation method thereof - Google Patents
9-hydroxy-risperidone increment type release osmotic pump tablet and preparation method thereof Download PDFInfo
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- CN107693502A CN107693502A CN201610659909.7A CN201610659909A CN107693502A CN 107693502 A CN107693502 A CN 107693502A CN 201610659909 A CN201610659909 A CN 201610659909A CN 107693502 A CN107693502 A CN 107693502A
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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
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/284—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
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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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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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
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
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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
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2086—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat
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Abstract
The invention belongs to technical field of medicine, discloses a kind of 9-hydroxy-risperidone increment type release osmotic pump tablet and preparation method thereof.The osmotic pump tablet is made up of double-deck core (being made up of medicated layer and boosting layer), the controlled release clothing (pellicle) with release hole and film-coating.Wherein, high molecular weight peo (mean molecule quantity 5,000,000~7,000,000) and a certain proportion of osmotic pressure active material have been used in medicated layer；2208 type hydroxypropyl methylcelluloses (3000~5600mPas of viscosity) and a certain proportion of osmotic pressure active material are used in boosting layer, realizes that active component is up to 24h incremental release using the water penetration of label every layer of different hydration rate and pellicle.Said preparation simplifies preparation technology, reduces technology difficulty, being capable of smooth industrialized production.
Description
Technical field
The invention belongs to technical field of medicine, is related to a kind of 9-hydroxy-risperidone increment type release osmotic pump tablet and its preparation side
Method.
Background technology
The problem of central nervous system (CNS) clinical drug application is present：1) adverse reaction is relatively common, and some adverse reactions can
Aggravate original nervous system cardinal symptom, patient tolerability is poor, and easily midway disables；2) ordinary preparation, which is taken, needs slowly initial stage
Incremental dose, reduces the generation of adverse reaction, but takes inconvenience；Increment type release system can be very good solve this problem,
It can steadily raise blood concentration, reduce blood plasma peak valley fluctuation of concentration, and Clinical practice does not need dose titration process, and keeps steady
The effect of determining and less adverse reaction, take simple, good patient compliance.
9-hydroxy-risperidone (9-hydroxy-risperidone), it is Risperidone active metabolite, is the derivative of benzoisoxazole, mainly passes through resistance
Disconnected serotonin 2A (5-HT2A) acceptor and dopamine D2(DA2) the psychotolytic effect of acceptor performance；9-hydroxy-risperidone is orally absolute
Bioavilability is 28%, and the half-life period that end eliminates phase is about 23h, apparent volume of distribution 487L, racemic 9-hydroxy-risperidone
Plasma protein binding rate be 74%, main adverse reaction includes cathisophobiaing with extrapyramidal system obstacle etc., external existing at present
The incremental release osmotic pump tablet listing of the medicine.
Typical Representative of the osmotic pump type controlled release preparation as sustained-release preparation, it is using osmotic pressure as drug release power, is released with zero level
Put a kind of preparation technique that dynamics is characterized.
Controlled releasing penetrant pump feature is obvious, can be really achieved the ideal effect that constant speed incrementally discharges, so that blood concentration temperature
Degree reduces peak valley phenomenon, substantially increases medication effect within the scope for the treatment of concentration；Spy with zero-order release
Sign, and rate of releasing drug is influenceed small, inside and outside drug release correlation by factors such as the pH value of media environment, gastrointestinal motility and foods
It is good；Blood medicine is steady, and adverse reaction is small；The advantages that medicining times are few, and patient's compliance is high.
United States Patent (USP) US20040092534 discloses a kind of three layers of osmotic pump tablet, is produced by Janssen companies, the tablet contains
One boosting layer and the different medicated layer of two content of dispersion, the semi-transparent clothing film of outsourcing is, it is necessary to which three layers are beaten chip technology and special three layers
Tablet machine equipment, complex process.
Chinese patent CN200910199425 disclose it is a kind of early stage about 5h can be incremented by and discharge, the later stage keeps constant delivery pa
Risperdal double-layer osmotic pumping system, its label are made up of promoting layer and medicated layer, outsourcing water solubility barrier gown and semi-transparent clothing film, control
Barrier gown thickness processed is to control the infiltration of moisture, and so as to reach the effect incrementally discharged early stage, but incremental release is only capable of maintaining 5h.
Chinese patent CN201110060811 discloses a kind of 9-hydroxy-risperidone osmotic pump tablet that can overcome pellicle aging phenomenon,
The patent research finds, using ethyl cellulose and PVP as pellicle filmogen, preferably with asymmetric type,
Pellicle aging phenomenon can be overcome, obtain stable rate of release, and reduce medicament residue, the patent mainly protects the bag
Clothing technique and prescription, the problem of not mentioning incremental release.
Chinese patent CN103271889 discloses double-deck incremental osmotic pump controlled release tablet of a kind of 9-hydroxy-risperidone and preparation method thereof, should
Patent research shows, in label medicated layer using intermediate molecular weight polyoxyethylene (mean molecule quantity 900,000~1,000,
000) with a certain proportion of osmo active substance, it may be such that medicine layer hydration rate is moderate, utilize double-deck core single coats
Make the release of active medicine that incremental releasing trend be presented substantially, and can maintain incrementally to discharge 14~24h, but point in its medicated layer
Son amount is the polyoxyethylene of middle-molecular-weihydroxyethyl.
At present with plug-type double layer osmotic pump maturation, optimum industry metaplasia the most in the osmotic pump preparation of release insoluble drug
Production, wherein high polymer material polyoxyethylene is most widely used, generally use low molecule amount polyoxyethylene as medicine layer supensoid agent,
High molecular weight peo promotes medicated layer drug suspension to be released from small delivery aperture as boosting layer intumescent material, boosting layer
Put, good release behavior can be achieved.
The content of the invention
The present invention be surprised to find when medicated layer polyoxyethylene molecular weight bring up to HMW (i.e. mean molecule quantity 5,000,
000~7,000,000) when, with reference to the controlled release mechanism technology of double layer osmotic pump, release, which is presented, is significantly incremented by releasing effect, this
Invention provides a kind of composition and preparation method of the double-layer osmotic pump tablet that can realize the release of 9-hydroxy-risperidone increment type.
Polyoxyethylene model and the mean molecule quantity table of comparisons used in the present invention is as follows：
| Sequence number | Model | Molecular weight |
| 1 | WSR Coagulant | 5,000,000 |
| 2 | WSR 303 | 7,000,000 |
The 9-hydroxy-risperidone increment type release osmotic pump tablet that the present invention is previously mentioned, it includes medicated layer and the double-layer tablets of boosting layer composition
Core and the semi-transparent clothing film of control release type.
Medicated layer is located in clothing film, adjoins release hole, and the drug containing layer composition includes active constituents of medicine, high-molecular-weight poly
Oxygen ethene and osmo active substance, and lubricant.
Active constituents of medicine includes 9-hydroxy-risperidone and its pharmaceutically acceptable salt, ester, its institute's accounting in drug containing layer composition
Example is 1%~20% (w/w), preferably 2%~10% (w/w).
The mean molecule quantity of high molecular weight peo is 5,000,000~7,000,000, and polyoxyethylene is in drug containing layer composition
Middle proportion is 10%~60% (w/w), preferably 10%~40% (w/w).
Osmo active substance includes sodium chloride, magnesium chloride, potassium chloride, magnesium sulfate, lactose, mannitol, sorbierite, glucose, sugarcane
Sugar, fructose or their mixture, proportion is 30%~90% (w/w) in drug containing layer composition, preferably 50%~
80% (w/w).
Lubricant includes stearic acid, magnesium stearate, talcum powder, sodium stearyl fumarate, rilanit special and their mixture,
Lubricant proportion in drug containing layer composition is 0~3% (w/w), preferably 0.1%~1.5% (w/w).
Boosting layer is located in clothing film, and away from release hole one end, boosting layer is by expanding material and nonessential osmotically active thing
Matter, colouring agent, lubricant.
Expanding material be hydroxypropyl methylcellulose, high molecular weight peo (mean molecule quantity 5,000,000~7,000,000) or
Their mixture, expanding material proportion in layer composition is promoted are 30%~100% (w/w), preferably 40%~
100% (w/w)
Osmo active substance includes sodium chloride, magnesium chloride, potassium chloride, magnesium sulfate, lactose, mannitol, sorbierite, grape
Sugar, sucrose, fructose or their mixture, proportion is 0~40% (w/w) in drug containing layer composition, preferably 5%~
30% (w/w).
Colouring agent can use the one or more in red ferric oxide, yellow ferric oxide, Brown Ferric Oxide, purple iron oxide, Black Rouge, with
And their mixture, proportion is 0~2% (w/w), preferably 0.1%~1% (w/w) in boosting layer composition.
Lubricant includes stearic acid, magnesium stearate, talcum powder, sodium stearyl fumarate, rilanit special and their mixture,
Lubricant proportion in drug containing layer composition is 0~3% (w/w), preferably 0.5%~2% (w/w).
Semipermeable clothing film is made up of control release type composition, comprising semipermeable polymer cellulose acetate and it is non-must
The pore-foaming agent needed, one or more release holes are equipped with medicated layer end surface,
Semi permeability clothing film can be dissolved in suitable solvent by control release type composition and be prepared into coating solution, using high-efficiency coating
Coating solution is sprayed to after label to dry and formed by machine.
Suitable solvent for preparing controlled release coat liquid includes water, acetone, ethanol, isopropanol, methanol, dichloromethane, acetic acid second
Ester, and their mixture.
Cellulose acetate proportion in control release type composition is 80%~100% (w/w), preferably 90%~100% (w/
w)。
Add pore-foaming agent in semi permeability clothing film, including it is polyethylene glycols, hydroxypropyl methylcellulose, polyvinyl alcohol, propane diols, sweet
Oil, PVP, and their mixture, for adjusting the Water permeability of semi permeability clothing film, the dosage of pore-foaming agent is 0~30%
(w/w), preferably 0~10% (w/w).
The time cycle that 9-hydroxy-risperidone increment type release osmotic pump tablet of the present invention can provide incremental rate of releasing drug is 14
~24h, preferably 16~20h.
" being incremented by rate of releasing drug " of the present invention refers to：Using drug release determination method, from described half within a period of time
The speed of active material is discharged in permeability clothing film, is increased over time, drug releasing rate increase.
Present invention also offers the method for preparing described 9-hydroxy-risperidone increment type release osmotic pump tablet, the preparation method include with
Under several steps：
1st, 9-hydroxy-risperidone, high molecular weight peo, osmo active substance are sieved, above material is weighed by recipe quantity, mixed
Uniformly；Wetting agent is prepared, prepares particle；The lubricant after sieving is weighed by recipe quantity, is well mixed with particle after above-mentioned drying,
For medicated layer particle；
2nd, dilatancy high polymer material, osmo active substance, colouring agent are sieved, weighs above material by recipe quantity, mixing is equal
It is even；Adhesive is prepared, prepares particle；The lubricant after sieving is weighed by recipe quantity, is well mixed with particle after above-mentioned whole grain, is
Boosting layer particle；
3rd, medicated layer particle and boosting layer particle are pressed into double-deck core using bi-layer tablet press；
4th, semipermeable polymers cellulose acetate, pore-foaming agent, water and acetone are weighed by recipe quantity, pore-foaming agent are dissolved in the water,
Acetone is added under being stirred in above-mentioned solution, is slowly added to cellulose acetate, stirring is formulated as controlled release coat liquid to dissolving；
5th, dried after label coating and remove residual solvent；
6th, a diameter of one or more holes are beaten in coating tablet medicated layer side laser or power auger, 9-hydroxy-risperidone is produced and is incremented by
Type discharges osmotic pump tablet.
Beneficial effects of the present invention are embodied in：
1st, medicine is discharged with Zero order rate, has unique release behavior, and medicine is discharged with progressively incremental rate of releasing drug all the time
Active constituents of medicine, therefore make blood concentration is stable to be maintained in the range for the treatment of concentration, peak valley phenomenon is reduced, makes medicine blood
Toxicity caused by concentration fluctuation is reduced to minimum, while can avoid the dose titration at medication initial stage again, significantly carries
The compliance of high patient；
2nd, reduce and take number, facilitate patient, be greatly enhanced the compliance of security, validity and patient that medicine uses；
3rd, rate of releasing drug is influenceed small by factors such as the pH value of media environment, gastrointestinal motility and foods, inside and outside drug release correlation
It is good；
4th, the present invention realizes incremental release using the osmosis pump control-release system of one layer of control release type clothing film of double-deck core outsourcing, prepares
Technique beats piece equipment and technology without using special three layers, without bag barrier gown process, significantly simplifies preparation technology,
Technology difficulty is reduced, can smoothly realize industrialized production.
Brief description of the drawings
Fig. 1 is the releasing curve diagram of embodiment 1, and incremental release is presented.
Fig. 2 is the releasing curve diagram of embodiment 2, and incremental release is presented.
Fig. 3 is the releasing curve diagram of embodiment 3, and incremental release is presented.
Fig. 4 is the releasing curve diagram of embodiment 4, and incremental release is presented.
Fig. 5 is the releasing curve diagram of commercially available 9-hydroxy-risperidone sustained release tablets (Rui reaches, 3mg specifications), and incremental release is presented.
Fig. 6 is the average rate of release figure of commercially available 9-hydroxy-risperidone sustained release tablets (Rui reaches, 3mg specifications)
Embodiment
The present invention will be further described in following examples：
Embodiment 1
Core formulation：
Medicated layer：
Pellicle prescription：
Cellulose acetate 50g
Macrogol 4000 1g
51g
Semi-transparent membrane solvent prescription：
Acetone 854.1g
Water 94.9g
Preparation technology：
(1) pre-process：Sodium chloride be crushed into 60 mesh sieves, red ferric oxide and magnesium stearate cross 60 mesh sieves respectively, standby；
(2) medicated layer：Supplementary material is weighed by recipe quantity, is well mixed；
(3) boosting layer：HPMC K4M, sodium chloride and red ferric oxide are weighed by recipe quantity, is well mixed, adds bonding
Agent is pelletized, and is dried, whole grain, is added magnesium stearate, is well mixed；
(4) medicated layer and boosting are laminated into double-layer tablets using bi-layer tablet press
(5) cellulose acetate and Macrogol 4000 are dissolved with acetone and water respectively, mixed.By label to high-efficiency coating machine
In, coating solution spray coating simultaneously increases weight to 14%, continues to dry to remove coating solvent.
(6) 9-hydroxy-risperidone increment type is produced in the laminated small delivery aperture for making a call to an a diameter of 1mm of drug containing using laser-beam drilling machine
Discharge osmotic pump tablet.
Press《Chinese Pharmacopoeia》Four dissolution rates of general rule 0931 of version in 2015 and drug release determination method, are filled using the second method (paddle method)
Put, with 0.1mol/L hydrochloric acid solutions, 500ml is dissolution medium, rotating speed 50rpm, medium temperature (37 ± 0.5) DEG C.Respectively at 2,
4th, 8,12,14,18 and 24h samples 5ml, while supplements mutually synthermal dissolution medium 5ml, 0.45 μm of miillpore filter of dissolution fluid
Filter laggard liquid phase detection.
Embodiment 2
Core formulation：
Medicated layer：
Pellicle prescription：
Cellulose acetate 50g
Macrogol 4000 1g
51g
Semi-transparent membrane solvent prescription：
Acetone 854.1g
Water 94.9g
Preparation technology：With embodiment 1, coating weight gain 14%.
Embodiment 3
Core formulation：
Medicated layer：
Pellicle prescription：
Cellulose acetate 50g
Macrogol 4000 1g
51g
Semi-transparent membrane solvent prescription：
Acetone 854.1g
Water 94.9g
Preparation technology：
(1) pre-process：Sodium chloride be crushed into 60 mesh sieves, red ferric oxide and magnesium stearate cross 60 mesh sieves respectively, standby；
(2) medicated layer：Supplementary material is weighed by recipe quantity, is well mixed；
(3) boosting layer：Auxiliary material is weighed by recipe quantity, is well mixed；
(4) medicated layer and boosting are laminated into double-layer tablets using bi-layer tablet press
(5) cellulose acetate and Macrogol 4000 are dissolved with acetone and water respectively, mixed.By label to high-efficiency coating machine
In, coating solution spray coating simultaneously increases weight to 14%, continues to dry to remove coating solvent.
(6) 9-hydroxy-risperidone increment type is produced in the laminated small delivery aperture for making a call to an a diameter of 1mm of drug containing using laser-beam drilling machine
Discharge osmotic pump tablet.
Embodiment 4
Core formulation：
Medicated layer：
Pellicle prescription：
Cellulose acetate 50g
Macrogol 4000 1g
51g
Semi-transparent membrane solvent prescription：
Acetone 854.1g
Water 94.9g
Preparation technology：With embodiment 3, coating weight gain 14%.
Claims (10)
1. a kind of 9-hydroxy-risperidone increment type discharges osmotic pump tablet, it includes double-deck core, controlled release clothing (band release hole) and film-coating,
It is characterized in that：Label is made up of medicated layer and boosting layer, and semipermeable clothing film is equipped with one in medicated layer end surface
Release hole, prepared by control release type composition, including semipermeable polymer cellulose acetate, described medicated layer, including medicine
Active component, high molecular weight peo and osmo active substance, boosting layer include expanding material；In described medicated layer
High molecular weight peo, its mean molecule quantity are 5,000,000~7,000,000.
A kind of 2. 9-hydroxy-risperidone increment type release osmotic pump tablet as claimed in claim 1, it is characterised in that：Active constituents of medicine,
Including 9-hydroxy-risperidone and its pharmaceutically acceptable salt, ester, its proportion in drug containing layer composition is 1%~10%.
A kind of 3. 9-hydroxy-risperidone increment type release osmotic pump tablet as claimed in claim 1, it is characterised in that：Described HMW
Polyoxyethylene, its mean molecule quantity be 5,000,000~7,000,000, in drug containing layer composition proportion be 10%~
60%.
A kind of 4. 9-hydroxy-risperidone increment type release osmotic pump tablet as claimed in claim 1, it is characterised in that：Described osmotically active
Material, including sodium chloride, potassium chloride, lactose, mannitol, sorbierite, glucose, sucrose, fructose or their mixture, containing
Proportion is 30%~90% in medicine layer composition.
A kind of 5. 9-hydroxy-risperidone increment type release osmotic pump tablet as claimed in claim 1, it is characterised in that：Described medicated layer bag
Containing lubricant, including stearic acid, magnesium stearate, talcum powder, sodium stearyl fumarate, rilanit special and their mixture,
Proportion is 0~3% in drug containing layer composition.
A kind of 6. 9-hydroxy-risperidone increment type release osmotic pump tablet as claimed in claim 1, it is characterised in that：Described boosting layer,
In clothing film, away from release hole one end, it is made up of, expands expanding material, osmo active substance, colouring agent and lubricant
Material includes hydroxypropyl methylcellulose, high molecular weight peo and their mixture, and expanding material is in layer composition is promoted
Proportion is 30%~100%, and osmo active substance includes sodium chloride, magnesium chloride, potassium chloride, magnesium sulfate, lactose, sweet dew
Alcohol, sorbierite, glucose, sucrose, fructose or their mixture, proportion is 0~40% in boosting layer composition,
Toner can use the one or more in red ferric oxide, yellow ferric oxide, Brown Ferric Oxide, purple iron oxide, Black Rouge, and they
Mixture, proportion is 0~2% in boosting layer composition, and lubricant includes stearic acid, magnesium stearate, talcum powder, hard
Fat fumaric acid sodium, rilanit special and their mixture, lubricant proportion in drug containing layer composition is 0~3%.
A kind of 7. 9-hydroxy-risperidone increment type release osmotic pump tablet as claimed in claim 1, it is characterised in that：Described semi permeability control
Release and contain pore-foaming agent in clothing film.
A kind of 8. 9-hydroxy-risperidone increment type release osmotic pump tablet as claimed in claim 1, it is characterised in that：Described is semipermeable
Clothing film, it is that can be dissolved in suitable solvent to be prepared into coating solution by control release type composition, will be wrapped using high-efficiency coating machine
Clothing liquid dries formation after spraying to label.
A kind of 9. 9-hydroxy-risperidone increment type release osmotic pump tablet as claimed in claim 8, it is characterised in that：It is described suitable molten
Agent is selected from water, acetone, ethanol, isopropanol, methanol, dichloromethane, ethyl acetate, and their mixture.
A kind of 10. preparation method of 9-hydroxy-risperidone increment type release osmotic pump tablet as claimed in claim 1, it is characterised in that including
Following steps：
(1) by 9-hydroxy-risperidone, high molecular weight peo, osmo active substance, it is well mixed, prepares particle；Add recipe quantity
Lubricant, it is well mixed with particle after above-mentioned drying, is medicated layer particle；Described high molecular weight peo, its average mark
Son amount is 5,000,000~7,000,000；
(2) dilatancy high polymer material, osmo active substance, colouring agent are well mixed, prepare particle, add the profit of recipe quantity
Lubrication prescription, it is well mixed with particle after above-mentioned whole grain, is boosting layer particle；
(3) medicated layer particle and boosting layer particle are pressed into double-deck core using bi-layer tablet press；
(4) semipermeable polymers cellulose acetate, pore-foaming agent, water and acetone are weighed by recipe quantity, pore-foaming agent are dissolved in the water,
Acetone is added under being stirred in above-mentioned solution, is slowly added to cellulose acetate, stirring is formulated as controlled release coat liquid to dissolving；
(5) dried after label coating and remove residual solvent；
(6) a diameter of one or more holes are beaten in coating tablet medicated layer side laser or power auger, 9-hydroxy-risperidone is produced and passs
Increasing type discharges osmotic pump tablet.
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| CN201610659909.7A CN107693502A (en) | 2016-08-08 | 2016-08-08 | 9-hydroxy-risperidone increment type release osmotic pump tablet and preparation method thereof |
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| CN201610659909.7A CN107693502A (en) | 2016-08-08 | 2016-08-08 | 9-hydroxy-risperidone increment type release osmotic pump tablet and preparation method thereof |
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| CN114983960A (en) * | 2021-12-29 | 2022-09-02 | 微研优仿医药科技(江苏)有限公司 | Pharmaceutical composition and preparation method thereof |
| CN115025058A (en) * | 2021-02-23 | 2022-09-09 | 成都同道慧宜生物医药科技有限公司 | Zero-order sustained release medicament and preparation method thereof |
| CN115350160A (en) * | 2022-10-20 | 2022-11-18 | 华润双鹤利民药业（济南）有限公司 | Paliperidone sustained-release preparation and preparation method thereof |
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| CN103271889A (en) * | 2013-05-23 | 2013-09-04 | 沈阳药科大学 | Novel paliperidone progressively-increased release osmotic pump preparation and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115025058A (en) * | 2021-02-23 | 2022-09-09 | 成都同道慧宜生物医药科技有限公司 | Zero-order sustained release medicament and preparation method thereof |
| CN115025058B (en) * | 2021-02-23 | 2024-01-26 | 成都同道慧宜生物医药科技有限公司 | Zero-order slow release medicament and preparation method thereof |
| CN114983960A (en) * | 2021-12-29 | 2022-09-02 | 微研优仿医药科技(江苏)有限公司 | Pharmaceutical composition and preparation method thereof |
| CN114983960B (en) * | 2021-12-29 | 2024-01-30 | 微研优仿医药科技(江苏)有限公司 | Pharmaceutical composition and preparation method thereof |
| CN115350160A (en) * | 2022-10-20 | 2022-11-18 | 华润双鹤利民药业（济南）有限公司 | Paliperidone sustained-release preparation and preparation method thereof |
| CN115350160B (en) * | 2022-10-20 | 2023-01-10 | 华润双鹤利民药业（济南）有限公司 | Paliperidone sustained-release preparation and preparation method thereof |
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Application publication date: 20180216 |