CN101491505A - Ropinirole hydrochloride sustained-release preparation and preparation method thereof - Google Patents
Ropinirole hydrochloride sustained-release preparation and preparation method thereof Download PDFInfo
- Publication number
- CN101491505A CN101491505A CNA2008100565482A CN200810056548A CN101491505A CN 101491505 A CN101491505 A CN 101491505A CN A2008100565482 A CNA2008100565482 A CN A2008100565482A CN 200810056548 A CN200810056548 A CN 200810056548A CN 101491505 A CN101491505 A CN 101491505A
- Authority
- CN
- China
- Prior art keywords
- coating
- ropinirole hydrochloride
- coated granule
- slow releasing
- releasing preparation
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Images
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a ropinirole hydrochloride slow-release preparation. At least one layer of a coating membrance containing a hydrophobic substance and a plastic excipient or a coating membrance containing the compositions and an enteric-coated macromolecular substance is used to coat particles containing ropinirole hydrochloride so as to form coated particles; and the coated particles and other excipients and disintegrating agents are encapsulated into a hard capsule or pressed into a tablet together.
Description
Affiliated technical field
The present invention relates to ropinirole hydrochloride slow releasing preparation and preparation method thereof.Said preparation is made up of pastille coated granule and excipient; wherein the clothing film of medicine-containing particle contains hydrophobic film-forming material, enteric solubility filmogen and plasticizer; composition, coating amount by changing coating membrane and have the ratio of the coated granule mixture of different coating amounts can be adjusted in the rate of release of ropinirole hydrochloride a suitable scope.Can more help patient's clinical application and treatment in lasting steady release in 24 hours or longer time.
Background technology
Ropinirole hydrochloride is a dopamine d 3 agonists, and clinical trial shows that ropinirole can be used for the treatment of early stage parkinson separately, also can share therapeutic advance phase parkinson with levodopa, and can reduce the consumption of levodopa.Ropinirole hydrochloride is developed by Britain SmithKline Beecham company, in 1996 in Britain's Initial Public Offering, be used for the treatment of parkinson clinically.Soon, France, the U.S. also get permission listing, trade name Requip.
Parkinson is a kind of carrying out property nervous system disease, it is characterized in that the selective dopaminergic neuron forfeiture in the black substance district of brain.Levodopa is a dopamine precursor, and the past is the parkinsonian main medicine of treatment always, but the patient produces involuntary movement such as complication such as the dyskinesia and dystonia after the medication.Use the dopamine agonist auxiliary treatment for using the patient of behind the levodopa complication taking place, keeping traditionally.Dopamine agonist treatment parkinson can singly be used, and also can be used as adjuvant drug and reduces the levodopa consumption, thereby reduce side effect.
The dopamine-receptor stimulant of present domestic use mainly contains pergolide, bromocriptine, piribedil etc., can not satisfy clinical demand far away.Ropinirole hydrochloride is the non-Ergota class of a selectivity dopamine D 3 receptor agonist.Be different from other dopamine agonist, this product has the simple chemical constitution similar to natural dopamine, acts on postsynaptic receptor in the striatum, the receptor-selective height.To early stage and progressive stage parkinson good result is all arranged.Treatment function of nervous system forfeiture aspect is better than levodopa.This product curative effect height, untoward reaction is few, and world's sales volume maintains the leading position always.Therefore this medicine will have bigger market in China.
At present the ropinirole preparation of listing mainly is the normal packet garment piece, needs use in one 3 times, and that disturbances in patients with Parkinson disease shows as is handicapped, and for the Parkinsonian who needs long-term prescription, general formulation has been not suitable for clinical practice.
The invention provides a kind of slow releasing preparation of ropinirole hydrochloride, took once in 1st, can keep the stable of blood drug level, long action time reduces administration number of times, has improved patient's compliance, is fit to the needs of clinical application.
Summary of the invention
The invention provides a kind of slow releasing preparation of ropinirole hydrochloride, it is characterized in that the granule will be mainly be made up of ropinirole hydrochloride carries out coating with one deck coating membrane at least, make coated granule, described coating rete is made up of a kind of lyophobic dust and a kind of plasticizer, selectively contain a kind of enteric polymer, altogether be loaded in hard capsule or compacting with a kind of disintegrating agent and other excipient this granule then.
The medicine-containing particle of mainly being made up of ropinirole hydrochloride used among the present invention is made up of ropinirole hydrochloride and the acceptable excipient of pharmacy, and relative hardness is higher, preferred 50 to the 1500 μ m of particle diameter, more preferably 500 to 1000 μ m.Medicine-containing particle specifically is made up of ropinirole hydrochloride and pharmaceutic adjuvant, pharmaceutic adjuvant is carboxymethyl starch sodium, microcrystalline Cellulose, lactose, sucrose, starch, polyvidone or cross-linking sodium carboxymethyl cellulose etc. for example, the preparation method of medicine-containing particle can be these powder of uniform mixing, the method for granulating of using general then.
According to the present invention, the preparation method that is used to form the coating solution of coating membrane can be dissolving or disperse a kind of hydrophobic film-forming material and a kind of plasticizer in a kind of lower alcohol (as ethanol), the amount of hydrophobic film-forming material is preferably 3%～10%, and the amount of plasticizer is preferably 10%～30%; Also can use the Aquacoat sold on the market (
), EUDRAGIT NE 30 D EUDRAGIT NE 30D (Eudragit
) and other coating solution.Preferred, ethyl or ethyl acrylate-methyl methacrylate.
Can use triethyl citrate, fatty acid glyceride, castor oil hydrogenated, fatty acid oil ester, Polyethylene Glycol or diethyl phthalate, optimization citric acid triethyl as plasticizer.
As enteric material, can use methacrylic acid copolymer, hydroxypropylmethyl cellulose phthalate, carboxymethylethylcellulose or acetyl cellulose phthalate etc., preferable methyl acrylic copolymer or hydroxypropylmethyl cellulose phthalate.
According to the present invention, utilize above-mentioned coating solution film forming on medicine-containing particle, can use conventional coating method, as fluidized bed coating etc.
The coating solution that is used for coating can wrap one or more layers clothing, and is in general preferably two-layer.For example when coating, water based coatings agent coating granule, further use alcohol radical coating solution coating, or with water based coatings liquid coating again behind the alcohol radical coating solution coating.Reuse alcohol radical coating solution coating behind the preferred water based coatings liquid coating.The weight ratio of coating is preferred 5%～60% in the coated granule, and more preferably 10%～30%.
Adopt method commonly used, with the coated granules hard capsule (gelatine capsule) of packing into, or with pack into hard capsule or be pressed into tablet of other excipient, wherein excipient can be carboxymethyl starch sodium, microcrystalline Cellulose, lactose, sucrose, starch, polyvidone or cross-linking sodium carboxymethyl cellulose etc.Coated granule can be made up of the different coated granules and the mixture of two or more types, and described dissimilar coated granule is as having different coating amounts, having different the coating composition or the different coating numbers of plies.
Ropinirole hydrochloride slow releasing preparation of the present invention is characterised in that when carrying out the dissolution in vitro test, disintegrate is coated granule and disperses immediately that medicine discharges gradually, plays slow releasing function from disintegrate and dispersed coated granule after on-test.By changing composition, the thickness of coating membrane and the ratio of the granulate mixture of different coating amounts of coating material, the dissolution rate of medicine can be adjusted in the suitable scope.
Slow releasing preparation of the present invention is easy to control the dissolution rate of ropinirole hydrochloride, so that when actual administration, be easy to a kind of like this slow releasing preparation of design, it can reach the optimal blood level rapidly after administration, keep effective haemoconcentration for a long time, the purpose that reached a day or be administered once at interval for more time.
Description of drawings
Accompanying drawing is ropinirole hydrochloride slow releasing tablet and capsular release in vitro curve chart.
The specific embodiment
The present invention now further describes embodiment as follows, but the scope of the invention is not limited to these embodiment.
Embodiment 1
(1) with 140g ropinirole hydrochloride powder, 40g carboxymethyl starch sodium and 800g lactose mix homogeneously, granulate with 10% 30 POVIDONE K 30 BP/USP 30, form medicine-containing particle, with the granule granulate, obtaining the 800g particle diameter is 16 to 30 purpose granules.
(2) use fluidized-bed coating machine, the coating solution atomizing that 180g is contained following composition is sprayed on the above-mentioned granule of 300g, makes coated granule, has used in the coating solution
With Eudragit L100-
Form weight (%)
Ethyl cellulose 11.6
Sodium lauryl sulphate 0.5
Triethyl citrate 4.7
Methacrylic acid copolymer 2.7
Distilled water 80.5
Amount to 100.0
(3) use fluidized-bed coating machine, the coating solution atomizing that 180g is contained following composition is sprayed on the above-mentioned granule of 300g, makes coated granule.
Form weight (%)
Ethyl cellulose 12.0
Sodium lauryl sulphate 0.5
Triethyl citrate 4.8
Methacrylic acid copolymer 2.0
Distilled water 80.7
Amount to 100.0
(4) use fluidized-bed coating machine, the coating solution atomizing that 150g is contained following composition is sprayed on the granule that obtains among the 200g (2), makes two-layer coated granule.
Form weight (%)
Ethyl cellulose 5.5
Hydroxypropylmethyl cellulose phthalate 2.5
Triethyl citrate 4.0
Distilled water 10.0
Ethanol 78.0
Amount to 100.0
(5) in the mode identical with (4), the atomizing of 150g coating solution is sprayed on the coated granule that obtains among the 200g (3), make and be surrounded by two-layer coated granule.
(6) with 600g lactose, carboxymethyl starch sodium 32g, 170g microcrystalline Cellulose mixing, be binding agent with 10% 30 POVIDONE K 30 BP/USP 30, wet granulation makes granule, behind the granulate, obtains 18 to 40 purpose granules.
(7) with the granule mix homogeneously that obtains among the coated granule that obtains among the 45g (4) and the 50g (3), then in flakes with the tablet machine compacting, heavy 200m (sheet 1) g of sheet.
(8) with the granule mix homogeneously that obtains among the coated granule that obtains among the 45g (4) and the 50g (3), then in flakes with the tablet machine compacting, the heavy 200mg of sheet.(sheet 2)
(9) coated granule that obtains in (4) directly is filled in the snap fit capsule loading amount 100mg (capsule 1).
(10) coated granule that obtains in (5) directly is filled in the snap fit capsule loading amount 100mg (capsule 2).
(11) the coated granule mix homogeneously that obtains in (4) and (5) with equivalent weight directly is filled in the snap fit capsule, loading amount 100mg (capsule 3).
Test example 1
Get this product, according to dissolution method (two appendix X of Chinese Pharmacopoeia version in 2005 C, the three therapeutic methods of traditional Chinese medicine), with 0.01mol/L hydrochloric acid solution 900ml is dissolution medium, and rotating speed is that per minute 50 changes, operation in accordance with the law, get solution 10ml in different time points, filter, get subsequent filtrate as need testing solution.Detect burst size with liquid chromatography, the result as shown in the figure.
From result shown in the figure as can be seen, the rate of release of sheet 1 and sheet 2, capsule 1 and capsule 2 has tangible different, but the release behavior of sheet 1 and capsule 1, sheet 2 and capsule 2 much at one, and the release behavior of capsule 3 is between capsule 1 and capsule 2.That is to say, might be by changing
With Eudragit L100-
Proportion of composing and arbitrarily change the release behavior of ropinirole hydrochloride, or change the ratio of the granulate mixture of different coating amounts, the dissolution rate of medicine can be adjusted in the suitable scope.And identical coated granule or be pressed into tablet or incapsulate, its release behavior can be owing to the pressure change of tabletting.
Ropinirole hydrochloride slow releasing preparation of the present invention is formed or the mixed proportion of the coated granule of coating amount by the different coatings of having of two or more types, and the release behavior of ropinirole hydrochloride can suitably be adjusted to required stripping behavior.And, might be easy to design the preparation that was administered once in a day.
Claims (8)
1. ropinirole hydrochloride slow releasing preparation, comprise (1) medicine-containing particle, mainly contain ropinirole hydrochloride and excipient, (2) one deck coating membrane layer at least, be made up of a kind of lyophobic dust and a kind of plasticity excipient, to form coated granule, wherein the coating amount in this coated granule accounts for 5%～60% of granule gross weight, (3) other excipient, described coated granule are loaded into hard capsule or are loaded into hard capsule or tablet forming together with excipient.
2. ropinirole hydrochloride slow releasing preparation according to claim 1, wherein this coated granule is to get by the granule of the hydrochloric ropinirole of one deck coating membrane coating at least, and described coating membrane is made up of a kind of hydrophobic material, a kind of enteric polymer and a kind of plasticizer.
3. ropinirole hydrochloride slow releasing preparation according to claim 1 and 2, wherein this coated granule is surrounded by two-layer.
4. ropinirole hydrochloride slow releasing preparation according to claim 1 and 2, wherein this coated granule is at least two kinds of mixture with coated granule of different coatings compositions or coating amount.
5. ropinirole hydrochloride slow releasing preparation according to claim 1 and 2, wherein the hydrophobic film-forming material 7 in the coating of this coated granule is a kind of insoluble polymers that are selected from ethyl cellulose and a kind of EUDRAGIT NE 30 D EUDRAGIT NE 30D.
6. ropinirole hydrochloride slow releasing preparation according to claim 1 and 2, wherein the plasticizer in the coating of this coated granule is triethyl citrate, castor oil hydrogenated, fatty acid glyceride, Polyethylene Glycol or diethyl phthalate.
7. ropinirole hydrochloride slow releasing preparation according to claim 2, wherein enteric material is a kind of methacrylic acid copolymer or hydroxypropylmethyl cellulose phthalate in the coating of this coated granule.
8. ropinirole hydrochloride slow releasing preparation according to claim 1, wherein excipient is carboxymethyl starch sodium, microcrystalline Cellulose, lactose, sucrose, starch, polyvidone or cross-linking sodium carboxymethyl cellulose.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2008100565482A CN101491505A (en) | 2008-01-22 | 2008-01-22 | Ropinirole hydrochloride sustained-release preparation and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2008100565482A CN101491505A (en) | 2008-01-22 | 2008-01-22 | Ropinirole hydrochloride sustained-release preparation and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101491505A true CN101491505A (en) | 2009-07-29 |
Family
ID=40922409
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2008100565482A Pending CN101491505A (en) | 2008-01-22 | 2008-01-22 | Ropinirole hydrochloride sustained-release preparation and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101491505A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102940605A (en) * | 2012-10-30 | 2013-02-27 | 开封白云制药有限公司 | Piribedil sustained release preparation and preparation method thereof |
-
2008
- 2008-01-22 CN CNA2008100565482A patent/CN101491505A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102940605A (en) * | 2012-10-30 | 2013-02-27 | 开封白云制药有限公司 | Piribedil sustained release preparation and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US5496561A (en) | Controlled release-initiation and controlled release-rate pharmaceutical composition | |
| CA2304110C (en) | Theophylline sustained release tablet | |
| RU2141822C1 (en) | New controlled-release granules and pharmaceutical preparations containing such granules | |
| MX2012011022A (en) | Controlled release dosage forms for high dose, water soluble and hygroscopic drug substances. | |
| TWI747810B (en) | Methods and compositions particularly for treatment of attention deficit disorder | |
| BRPI0714915A2 (en) | pharmaceutical compositions; pharmaceutical dosage forms; and process for the preparation of a pharmaceutical composition | |
| WO2000009133A1 (en) | Sustained release oral preparations of fasudil hydrochloride | |
| JPH0759506B2 (en) | Pharmaceutical formulation | |
| US20110311626A1 (en) | Controlled release compositions comprising anti-cholinergic drugs | |
| CN102369000A (en) | Pharmaceutical composition comprising one or more fumaric acid esters | |
| Pan et al. | Novel compaction techniques with pellet-containing granules | |
| KR20120130292A (en) | Extended release Formulations of Rasagiline and Uses thereof | |
| AU2010277207A1 (en) | Multi-layered, multiple unit pharmaceutical compositions | |
| TW201206501A (en) | Pharmaceutical compositions comprising hydromorphone and naloxone | |
| CA2697437A1 (en) | Pharmaceutical combination of aliskiren and valsartan | |
| CN110123782A (en) | Hollow particle containing drug | |
| WO2012101653A2 (en) | Modified release pharmaceutical compositions memantine | |
| CN101646422A (en) | Extended-release dosage form | |
| MX2010011409A (en) | Solid oral form with dual release profile, containing multiparticulates. | |
| TW202143972A (en) | A multiple formulation of ticagrelor | |
| CN101636153A (en) | Time-specific delayed/pulsatile release dosage forms | |
| CN101099762B (en) | Blood pressue lowering sustained-release preparation with chrysanthemum flower and pearl | |
| CN101491505A (en) | Ropinirole hydrochloride sustained-release preparation and preparation method thereof | |
| CN102247326B (en) | Oral chronopharmacologic drug delivery mini-pill preparation of propranolol and its salts | |
| CN101953833A (en) | Slowly-controlled release formulation containing rizatriptan benzoate, preparation method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C12 | Rejection of a patent application after its publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20090729 |