CN101756934A - Preparation method for venlafaxine sustained-release preparations - Google Patents
Preparation method for venlafaxine sustained-release preparations Download PDFInfo
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- CN101756934A CN101756934A CN200810204299A CN200810204299A CN101756934A CN 101756934 A CN101756934 A CN 101756934A CN 200810204299 A CN200810204299 A CN 200810204299A CN 200810204299 A CN200810204299 A CN 200810204299A CN 101756934 A CN101756934 A CN 101756934A
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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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- 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
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
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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
- A61K9/5026—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
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Abstract
The invention provides a preparation method for venlafaxine sustained-release preparations, which adopts a preparation technique of squeezing granulating to pulverize the active ingredients of medicines, controlling the particle size range, taking a sugar core as a carrier, pasting the active ingredients of medicines uniformly on the sugar core, and then coating the obtained pellets. The preparation method for venlafaxine sustained-release preparations realizes to control coating films and pellet spherality, and guarantees to control the venlafaxine sustained-release stability and repeatability under the situation of guaranteeing that the venlafaxine crystal form is not changed. The preparation of the invention provides continuous release in 24 hours in the form of single dose, reduces disgusting degree and generation of sickness, and can realize more compact curative effect concentration scope control. The technique of the invention is simple and easy to be implemented, and is suitable for industrial production.
Description
Technical field
The present invention relates to the preparation method of pharmaceutical preparation, be specifically related to the preparation method of venlafaxine sustained-release preparations.
Background technology
Venlafaxine is mainly used in treatment all kinds depression, comprises depression and generalized anxiety disorder with anxiety.Because advantage such as have determined curative effect, untoward reaction is few, onset is rapid, interact between the medicine less has been widely used in depression, especially the treatment of serious symptom depression at present.Venlafaxine also has treatment geratic period depression, obsession, attention deficit hyperactivity disorder, anxiety neurosis, social phobia, schizoid curative effect in the treatment depression.Use and improve drug effect, the long-acting slow-release capsule preparations listing of existing venlafaxine for ease of the patient.Existing commercially available venlafaxine sustained-release capsule employing is extruded round as a ball mode and made the pastille micropill, micropill is carried out the preparation process of sustained release coating again, and is too loaded down with trivial details, is unfavorable for suitability for industrialized production.
Summary of the invention
The technical problem to be solved in the present invention is to overcome above-mentioned weak point, sets up a kind of preparation method of long-acting slow-release capsule preparations of venlafaxine, and quality controllable to this preparation process.
The invention provides a kind of preparation method of venlafaxine sustained-release preparations.This method comprises the following steps:
(1) medicine-feeding: venlafaxine hydrochloride is micronized to the 0-20 micron, with 150-180 part isopropyl alcohol as the medicine-feeding disperse medium, the solvent medicine-feeding, 60 parts of venlafaxine hydrochlorides and binding agent 2-5 part ethyl cellulose, 0-3 part hydroxypropyl methylcellulose are dispersed in the isopropyl alcohol, in 25-45 part specification of under 25-35 ℃ the temperature solvent spray being added medicine to is on the 30-35 purpose sucrose ball core, dry 5-10 minute, obtain the piller of adding medicine to:
(2) coating: 10-15 part Pulvis Talci is dispersed in the water, form uniform Pulvis Talci suspension, mix with 30-50 part polyacrylic resin aqueous dispersion, under 25-35 ℃ temperature with this coating solution spraying 70-80 part medicine-feeding piller of adding medicine to, sampling respectively, dry 5-10 minute, obtain coated micropill;
(3) make capsule: coated micropill and Pulvis Talci is even with 50: 1 mixed, put into 50-55 ℃ of baking oven, aging 24 hours, sieve, sieve removes unnecessary Pulvis Talci, keeps the micropill of 0.71-1.2 millimeter, in the hard gelatin capsule of packing into according to a conventional method.
Compare with the preparation process of existing extruder grain, technology of the present invention is more simple, saves cost, and can be controlled greatly to the rate of release of medicine.
The present invention is with the active constituents of medicine fine-powdered, and the controlling particle size scope is a carrier with sugared core, the medicine-feeding, with active constituents of medicine evenly attached on the sugared core, then to gained micropill coating.Because drug releasing rate is relevant with coating membrane thickness, the drug release uniformity is near spherical relevant with micropill, the present invention has realized coating membrane and spherical be somebody's turn to do controlled of micropill, just can guarantee to carry out controlled to the stable repeatability that venlafaxine discharges under the situation that the venlafaxine crystal formation do not transform.
According to the inventive method, provide to contain the encapsulated preparation of venlafaxine hydrochloride as the lasting release of active medicine component, said preparation provides in 24 hours scope with single dose form and continues to discharge.By taking venlafaxine sustained-release preparations of the present invention, with every day repeatedly medication compare, reduced nauseating degree and the vomiting followed when repeatedly taking medicine every day by adaptations and taken place, can realize curative effect concentration range control more closely.
Concrete effect of the present invention is as follows:
Under the condition that does not change crystal formation, the fine-powdered pharmaceutically active substance evenly adds medicine to sugared core to the 0-20 micron, is illustrated in fig. 1 shown below: medicine-feeding back medicated core farthest is evenly spherical, thereby it is controlled to guarantee that spraying adds in the membrane process uniformity of film.Rate of release at the dispose procedure Chinese medicine of medicine is decided by film, and the uniformity of film is controlled, has guaranteed the repeatability of pharmaceutical preparation technology and the stability of pharmaceutical preparation.Simultaneously in order to increase the lubricated and anti-adhesion effectiveness between the granule, will add medicine to afterwards that granule mixes with Pulvis Talci, mix and sieve after drug particles as shown in Figure 2.
The present invention adopts the preparation process of extruder grain, compares, and technology of the present invention is more simple, saves cost, and can be controlled greatly to the rate of release of medicine, is suitable for suitability for industrialized production.
Description of drawings
Medicated core form after Fig. 1 adds medicine to
Fig. 2 adds the medicated core form behind the Pulvis Talci
Fig. 3 is by embodiment gained related data, with existing brand medicine
The stripping data compare, dissolution rate is controlled within the specific limits.
Wherein legend key is successively from top to bottom: embodiment 1, the brand medicine, and embodiment 2.
Abscissa be dissolution time (hour): length overall is 24 hours, is spaced apart 2 hours.
Vertical coordinate is principal agent rate of release (%): length overall is 100, is spaced apart 10.
Fig. 4 embodiment product, 3 months accelerated tests stability experiments, the stripping curve contrast, it is stable that rate of release keeps.
Wherein legend key is successively from top to bottom: 0 month, and January, February, March.
Abscissa be dissolution time (hour): length overall is 24 hours, is spaced apart 2 hours.
Vertical coordinate is principal agent rate of release (%): length overall is 100, is spaced apart 10.
The specific embodiment
Embodiment 1:
(1) solvent medicine-feeding: the venlafaxine hydrochloride fine-powdered is arrived the 15-20 micron, get the 300g venlafaxine hydrochloride and binding agent 25g ethyl cellulose is dispersed in the isopropyl alcohol, the 175g sucrose ball core (specification is the 30-35 order) of under 30 ℃ temperature, solvent spray being added medicine to, dry 5-10 minute, obtain the piller of adding medicine to.
(2) coating: the 70g Pulvis Talci is dispersed in the water, form uniform Pulvis Talci suspension, mix with 233g polyacrylic resin aqueous polymer dispersion, under 30 ℃ temperature with this coating solution spraying 360g medicine-feeding piller of adding medicine to, in coating weightening finish 12%-28% sampling, dry 5-10 minute, obtain micropill.
(3) preparation capsule: the micropill behind the coating and Pulvis Talci with 50: 1 weight ratio mix homogeneously, are put into 50-55 ℃ of baking oven, aging 24 hours, sieve, sieve removes unnecessary Pulvis Talci, and the micropill of reservation 0.71-1.2 millimeter is in its hard gelatin capsule of packing in a usual manner.
| Medicine-feeding piller venlafaxine content | ??41.54％ |
| Venlafaxine content in the micropill behind the coating | ??37.2％ |
Embodiment 2:
(1) solvent medicine-feeding: 300g venlafaxine hydrochloride and binding agent 25g ethyl cellulose are dispersed in the isopropyl alcohol, and the 175g sucrose ball core (specification is the 30-35 order) of under 30 ℃ temperature solvent spray being added medicine to dry 5-10 minute, obtains the piller of adding medicine to.
(2) coating: the 55g Pulvis Talci is dispersed in the water, form uniform Pulvis Talci suspension, mix with the aqueous polymer dispersion that contains the 183g polyacrylic resin, under 30 ℃ temperature with this coating solution spraying 390g medicine-feeding piller of adding medicine to, in coating weightening finish 12%-28% sampling, dry 5-10 minute, obtain micropill.
(3) preparation capsule: the micropill behind the coating and Pulvis Talci with 50: 1 weight ratio mix homogeneously, are put into 50-55 ℃ of baking oven, aging 24 hours, sieve, sieve removes unnecessary Pulvis Talci, and the micropill of reservation 0.71-1.2 millimeter is in its hard gelatin capsule of packing in a usual manner.
| Medicine-feeding piller venlafaxine content | ??47.2％ |
| Venlafaxine content in the micropill of coating weightening finish back | ??37.2％ |
Embodiment 3:
(1) solvent medicine-feeding: 300g venlafaxine hydrochloride and binding agent 25g ethyl cellulose, 10g hydroxypropyl methylcellulose are dispersed in the isopropyl alcohol, the 165g part sucrose ball core (specification is the 30-35 order) of under 30 ℃ temperature, solvent spray being added medicine to, dry 5-10 minute, obtain the piller of adding medicine to.
(2) coating: the 70g Pulvis Talci is dispersed in the water, form uniform Pulvis Talci suspension, mix with the aqueous polymer dispersion that contains the 233g polyacrylic resin, under 30 ℃ temperature with this coating solution spraying 360g medicine-feeding piller of adding medicine to, in coating weightening finish 12%-28% sampling, dry 5-10 minute, obtain micropill.
(3) preparation capsule: the micropill behind the coating and Pulvis Talci with 50: 1 weight ratio mix homogeneously, are put into 50-55 ℃ of baking oven, aging 24 hours, sieve, sieve removes unnecessary Pulvis Talci, and the micropill of reservation 0.71-1.2 millimeter is in its hard gelatin capsule of packing in a usual manner.
| Medicine-feeding piller venlafaxine content | ??47.8％ |
| Venlafaxine content in the micropill behind the coating | ??38.1％ |
By the foregoing description gained related data, with existing brand medicine
The stripping data compare, dissolution rate is controlled within the specific limits.(see figure 3)
3 months accelerated tests stability experiments of embodiment, stripping curve contrasts as shown in Figure 4, and it is stable that rate of release keeps.
Claims (2)
1. the preparation method of a venlafaxine sustained-release preparations is characterized in that, this method comprises the following steps:
(1) medicine-feeding: venlafaxine hydrochloride, with 150-180 part isopropyl alcohol as the medicine-feeding disperse medium, the solvent medicine-feeding, 50-70 part venlafaxine hydrochloride and binding agent 2-5 part ethyl cellulose, 0-3 part hydroxypropyl methylcellulose are dispersed in the isopropyl alcohol, 25-45 part sucrose ball core specification of under 25-35 ℃ temperature solvent spray being added medicine to is the 30-35 order, dry 5-10 minute, obtain the piller of adding medicine to;
(2) coating: 10-15 part Pulvis Talci is dispersed in the water, form uniform Pulvis Talci suspension, mix with 30-50 part polyacrylic resin aqueous dispersion, under 25-35 ℃ temperature with this coating solution spraying 70-80 part medicine-feeding piller of adding medicine to, sampling respectively, dry 5-10 minute, obtain coated micropill;
(3) make capsule: coated micropill and Pulvis Talci is even with 50: 1 mixed, put into 50-55 ℃ of baking oven, aging 24 hours, sieve, remove Pulvis Talci, keep the micropill of 0.71-1.2 millimeter, in the hard gelatin capsule of packing into according to a conventional method.
2. according to the preparation method of the described venlafaxine sustained-release preparations of claim 1, it is characterized in that, during described step (1) medicine-feeding, earlier venlafaxine hydrochloride is micronized to the 0-20 micron.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200810204299A CN101756934A (en) | 2008-12-10 | 2008-12-10 | Preparation method for venlafaxine sustained-release preparations |
| PCT/CN2009/075096 WO2010066159A1 (en) | 2008-12-10 | 2009-11-23 | A preparation method of venlafaxine sustained release formulation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200810204299A CN101756934A (en) | 2008-12-10 | 2008-12-10 | Preparation method for venlafaxine sustained-release preparations |
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| Publication Number | Publication Date |
|---|---|
| CN101756934A true CN101756934A (en) | 2010-06-30 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200810204299A Pending CN101756934A (en) | 2008-12-10 | 2008-12-10 | Preparation method for venlafaxine sustained-release preparations |
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| Country | Link |
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| CN (1) | CN101756934A (en) |
| WO (1) | WO2010066159A1 (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102085197A (en) * | 2010-12-14 | 2011-06-08 | 北京万生药业有限责任公司 | Venlafaxine slow-release preparation and preparation method thereof |
| CN103054835A (en) * | 2013-01-30 | 2013-04-24 | 张晓明 | Venlafaxine sustained-release capsule and preparation process thereof |
| CN109200032A (en) * | 2018-10-29 | 2019-01-15 | 湖南洞庭药业股份有限公司 | High drug load venlafaxine hydrochloride sustained-release pellet composition and spansule and preparation method |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103893153B (en) * | 2014-04-17 | 2016-04-13 | 石家庄市华新药业有限责任公司 | A kind of venlafaxine hydrochloride slow-release capsule and preparation method thereof |
| CN113041235B (en) * | 2019-12-27 | 2023-05-02 | 西安远大德天药业股份有限公司 | Venlafaxine hydrochloride sustained release agent, preparation method thereof, venlafaxine hydrochloride sustained release capsule and application thereof |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0307277D0 (en) * | 2003-03-28 | 2003-05-07 | Biochemie Gmbh | Organic compounds |
| US7470435B2 (en) * | 2003-11-17 | 2008-12-30 | Andrx Pharmaceuticals, Llc | Extended release venlafaxine formulation |
| BRPI0418283A (en) * | 2004-02-04 | 2007-05-02 | Alembic Ltd | prolonged release formulation and process for preparing an extended release formulation |
-
2008
- 2008-12-10 CN CN200810204299A patent/CN101756934A/en active Pending
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2009
- 2009-11-23 WO PCT/CN2009/075096 patent/WO2010066159A1/en active Application Filing
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102085197A (en) * | 2010-12-14 | 2011-06-08 | 北京万生药业有限责任公司 | Venlafaxine slow-release preparation and preparation method thereof |
| CN102085197B (en) * | 2010-12-14 | 2013-08-14 | 北京万生药业有限责任公司 | Venlafaxine slow-release preparation and preparation method thereof |
| CN103054835A (en) * | 2013-01-30 | 2013-04-24 | 张晓明 | Venlafaxine sustained-release capsule and preparation process thereof |
| CN103054835B (en) * | 2013-01-30 | 2014-07-23 | 张晓明 | Venlafaxine sustained-release capsule and preparation process thereof |
| CN109200032A (en) * | 2018-10-29 | 2019-01-15 | 湖南洞庭药业股份有限公司 | High drug load venlafaxine hydrochloride sustained-release pellet composition and spansule and preparation method |
| CN109200032B (en) * | 2018-10-29 | 2022-01-14 | 湖南洞庭药业股份有限公司 | High drug-loading venlafaxine hydrochloride sustained-release pellet composition, sustained-release capsule and preparation method |
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| Publication number | Publication date |
|---|---|
| WO2010066159A1 (en) | 2010-06-17 |
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Open date: 20100630 |