CN103191082A - Venlafaxine hydrochloride spansule and preparation method thereof - Google Patents
Venlafaxine hydrochloride spansule and preparation method thereof Download PDFInfo
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- CN103191082A CN103191082A CN 201310137906 CN201310137906A CN103191082A CN 103191082 A CN103191082 A CN 103191082A CN 201310137906 CN201310137906 CN 201310137906 CN 201310137906 A CN201310137906 A CN 201310137906A CN 103191082 A CN103191082 A CN 103191082A
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Abstract
The invention discloses a venlafaxine hydrochloride spansule and a preparation method thereof. According to the existing method, aqueous dispersion is used for coating, and venlafaxine hydrochloride generates migration during the coating process due to high water solubility of venlafaxine hydrochloride, so that venlafaxine hydrochloride is possible to become a pore-forming agent to result in overquick release of venlafaxine hydrochloride if the thickness of a coating film is insufficient. The venlafaxine hydrochloride spansule disclosed by the invention is characterized in that the medicated micro-pill comprises a medicated pill core, an isolating layer coating the medicated pill core and a release control layer coating the isolating layer, wherein the medicated pill core is prepared from the following ingredients in percentage by weight: 30-60% of venlafaxine hydrochloride, 30-80% of filler, 1-20% of release skeleton material and 1-10% of adhesive. According to the invention, such technical problems as potential safety hazard to operators and high demands on equipment caused by utilizing organic solvents, namely dichloromethane and ethanol, for coating are completely solved.
Description
Technical field
The present invention relates to the slow releasing capsule field, specifically a kind of venlafaxine hydrochloride sustained-release capsule and preparation method thereof.
Background technology
VENLAFAXINE HCL, its chemistry is by name: (±)-1-[2-(dimethylamino)-the 1-(4-anisyl) ethyl]-cyclohexanol hydrochloridumi, be a kind of novel antidepressants, be that first of clinical practice has both the medicine of 5-hydroxy tryptamine (5-HT) and norepinephrine (NE) reuptake inhibition, but almost do not have affinity with epinephrine al, a2, beta receptor, M cholinoceptor and histamine H l receptor.Because its special pharmacological action, VENLAFAXINE HCL has obtained extensive use clinically in psychiatric department, is used for the treatment of all kinds depression, comprises the depression with anxiety, and VENLAFAXINE HCL is the first-line treatment medicine of serious symptom depression at present.
Chinese patent CN97109594.9 discloses a kind of preparation method of venlafaxine hydrochloride sustained-release capsule, behind VENLAFAXINE HCL, microcrystalline Cellulose and hydroxypropyl emthylcellulose mix homogeneously, prepare micropill by extruding round as a ball method, adopt dichloromethane and dehydrated alcohol to make solvent then, ethyl cellulose dissolved and hydroxypropyl emthylcellulose are done coating material.The organic solvent dichloromethane that the method adopts contains severe toxicity, and ethanol is inflammable and explosive, and there is potential safety hazard in operator, and also higher to the requirement of equipment.
Because VENLAFAXINE HCL is soluble in water, dissolubility is 1.5g/mL in the water, so in order to prevent that medicine from moving in experimentation, Chinese patent CN200910162006.8 mentions in the micropill prescription and adds the sustained-release matrix material, be that binding agent prepares micropill with the acrylic resin aqueous dispersion then, reach the purpose of slow release in skin bag controlled release layer, extrude the adhesive tacky that round as a ball heat radiation causes in order to reduce, also need further to improve and extrude spheronizator, its process complexity, and having relatively high expectations to equipment.Chinese patent CN201010588764.9 mentions and adopts ball core medicine-feeding legal system to be equipped with the venlafaxine hydrochloride sustained-release micropill, crude drug, microcrystalline Cellulose, ethyl cellulose, dextrin etc. are mixed as the medicine-feeding layer, wherein ethyl cellulose is as blocker in the medicine-feeding layer, and the external acrylic resin reaches the purpose of slow release as controlled release layer.Chinese patent CN201110270903.8 discloses and has adopted sealing coat and controlled release layer bilayer to control the way of drug release.Above-mentioned patent all is to adopt aqueous dispersion to carry out coating, because the highly-water-soluble of VENLAFAXINE HCL, cause VENLAFAXINE HCL when coating, to move, under the situation of coating membrane thickness low LCL, VENLAFAXINE HCL may become to the hole agent, cause the release of VENLAFAXINE HCL too fast, can cause cost too high and increase coating thickness.
Summary of the invention
Technical problem to be solved by this invention is to overcome the defective that above-mentioned prior art exists, a kind of venlafaxine hydrochloride sustained-release capsule is provided, said preparation is to design at the character characteristics of VENLAFAXINE HCL, and can satisfy every requirements such as slow release in 24 hours, stability, industrial-scale production simultaneously.
For this reason, the present invention adopts following technical scheme: a kind of venlafaxine hydrochloride sustained-release capsule, comprise capsule shells and place the pastille micropill of capsule shells, it is characterized in that described pastille micropill comprises and contain pill core, wrap in and contain the outer sealing coat of pill core and wrap in the outer controlled release layer of sealing coat
The described pill core that contains is made by the component of following weight percentage ratio:
VENLAFAXINE HCL 30-60%,
Filler 30-80%,
Sustained-release matrix material 1-20%,
Binding agent 1-10%;
The filler that contains in the pill core of the present invention is one or more in microcrystalline Cellulose, lactose, the pregelatinized Starch; The sustained-release matrix material is one or more in full-bodied hydroxypropyl emthylcellulose, ethyl cellulose, the acrylic resin; Binding agent is one or more in low viscous hydroxypropyl emthylcellulose, Aquacoat, the acrylic resin aqueous dispersion.
It is that 0-10%(is to contain pill core weight that sealing coat of the present invention comprises weight ratio) full-bodied hydroxypropyl emthylcellulose.Find that by a large amount of experiment the size of hydroxypropyl emthylcellulose molecular weight in the sealing coat and content have bigger influence to the release of venlafaxine, wherein the influence to VENLAFAXINE HCL under the situation of high-load of low viscous hydroxypropyl emthylcellulose is also little, and full-bodied hydroxypropyl emthylcellulose has remarkable influence to the release of the VENLAFAXINE HCL of the zero hour.As long as control the coating parameter of controlled release layer and the purpose that coatings thickness also can reach slow release well even do not add sealing coat.Do not having to need more outer coating and more accurate coating operation under the situation of sealing coat.
It is that 10-50%(is in the ground floor coat weight that controlled release layer of the present invention comprises weight) the extended release coatings film, described extended release coatings film comprises: insoluble polymer 50-70%; To the hole agent be 0-10%, antiplastering aid 20-40%.Insoluble polymer of the present invention is one or several in Aquacoat, the acrylic resin aqueous dispersion; To the hole agent be in hydroxypropyl emthylcellulose, lactose, sodium chloride, potassium chloride, Polyethylene Glycol, the polyvinylpyrrolidone one or more; Antiplastering aid is one or more in Pulvis Talci, the glyceryl monostearate.
The preparation method of capsule of the present invention is as follows:
1) with behind VENLAFAXINE HCL, filler and the slow release framework material mix homogeneously, use centrifugal granulation or extrude spheronization to prepare micropill, in the micropill preparation process, add binding agent, micropill is dried, sieving obtains containing pill core;
2) will contain pill core and place fluid bed, and adopt the method for end spray to wrap sealing coat and controlled release layer respectively, heat treatment obtains the pastille micropill of VENLAFAXINE HCL;
3) during being incapsulated, the pastille micropill namely gets the venlafaxine hydrochloride sustained-release capsule.
The present invention adopts centrifugal granulating and extrudes the pill core that contains that round as a ball two kinds of technologies prepare VENLAFAXINE HCL, and adopt aqueous dispersion film control packaging technique that this ball core is carried out coating, thoroughly solved original employing organic solvent dichloromethane, ethanol is made solvent and is carried out coating, cause and require a high-technology difficult problem to what operator existed potential safety hazard and equipment, and reached to imported medicine " Efexor XR " and had similar release curve, be easy to suitability for industrialized production, used cost of supplementary product is cheap, be easy to get, and quality is more stable.
Description of drawings
Fig. 1 is product and the stripping curve comparison diagram of Efexor XR in water of the embodiment of the invention 1 gained.
Fig. 2 is product and the stripping curve comparison diagram of Efexor XR in water of the embodiment of the invention 2 gained.
Fig. 3 is product and the stripping curve comparison diagram of Efexor XR in water of the embodiment of the invention 3 gained.
Fig. 4 is product and the stripping curve comparison diagram of Efexor XR in water of the embodiment of the invention 4 gained.
Fig. 5 is product and the stripping curve comparison diagram of Efexor XR in water of the embodiment of the invention 5 gained.
Fig. 6 is product and the stripping curve comparison diagram of Efexor XR in water of the embodiment of the invention 6 gained.
Fig. 7 is product and the stripping curve comparison diagram of Efexor XR in water of the embodiment of the invention 7 gained.
The specific embodiment
The invention will be further described below in conjunction with Figure of description and embodiment.
Embodiment 1
The prescription that contains pill core:
Preparation method is as follows:
With microcrystalline Cellulose, hydroxypropyl emthylcellulose and VENLAFAXINE HCL mix homogeneously.Put in the extruder with 5% polyvinylpyrrolidonesolution solution soft material processed and to extrude (screen cloth diameter 0.8mm, extruded velocity: 25rpm), with extruded material as for round as a ball in the spheronizator (rotating speed 600-1000rpm, 500 seconds round as a ball time).With material in air dry oven 40 ℃-60 ℃ dry 2-4 hour, sieve, screen out greater than 16 orders and be less than 30 purpose ball cores.
The coating prescription:
The coating solution method for making: hydroxypropyl emthylcellulose is added to the water, adds Pulvis Talci under the cutter effect, this solution is added among the Eudragit NE30D, stirring gets final product.
Coating operation: get 500g and contain pill core and adopt the capable coating of spirt at the bottom of the fluid bed, preparation slow-release micro-pill.The coating weightening finish is (calculating by polymer weight) 30%, 40%, 50%.
Release is investigated: carry out release by the product of Chinese import of drugs registered standard X20000237 and investigate, and compare with Wyeth pharmaceuticals product Efexor XR (Efexor XR).
The release of table 1 embodiment 1
Embodiment 2
The prescription that contains pill core:
Preparation method: with microcrystalline Cellulose and VENLAFAXINE HCL mix homogeneously.Do binding agent with 3% Gonak, use centrifugal granulation to prepare micropill.With material in air dry oven 40 ℃-60 ℃ dry 2-4 hour, sieve, screen out greater than 16 orders and be less than 30 purpose ball cores.
The coating prescription:
Coating operation: the 30-16 purpose of getting 500g embodiment 2 preparations contains pill core, with the method for end spray respectively with sealing coat and controlled release layer coating, the preparation slow-release micro-pill.Coating weightening finish (calculating by polymer weight) 30%, 40%.
Release is investigated: carry out release by the product of Chinese import of drugs registered standard X20000237 and investigate, and compare with Wyeth pharmaceuticals product Efexor XR (Efexor XR).
The release of table 2 embodiment 2
Embodiment 3
The prescription that contains pill core:
Preparation method: with microcrystalline Cellulose and VENLAFAXINE HCL mix homogeneously.Do binding agent with 3% Gonak, use centrifugal granulation to prepare micropill.With material in air dry oven 40 ℃-60 ℃ dry 2-4 hour, sieve, screen out greater than 16 orders and be less than 30 purpose ball cores.
The coating prescription:
Coating operation: get the 30-16 purpose ball core of 500g embodiment 3 preparations, with the method for end spray respectively with sealing coat and controlled release layer coating, the preparation slow-release micro-pill.Coating weightening finish (calculating by polymer weight) 30%, 40%.
Release is investigated: carry out release by the product of Chinese import of drugs registered standard X20000237 and investigate, and compare with Wyeth pharmaceuticals product Efexor XR (Efexor XR).
The release of table 3 embodiment 3
The prescription that contains pill core:
Preparation method: with microcrystalline Cellulose and VENLAFAXINE HCL mix homogeneously.Do binding agent with 3% Gonak, use centrifugal granulation to prepare micropill.With material in air dry oven 40 ℃-60 ℃ dry 2-4 hour, sieve, screen out greater than 16 orders and be less than 30 purpose ball cores.
The coating prescription:
Coating operation: get the 30-16 purpose ball core of 500g embodiment 4 preparations, with the method for end spray respectively with sealing coat and controlled release layer coating, the preparation slow-release micro-pill.Coating weightening finish (calculating by polymer weight) 20%, 30%.
Release is investigated: carry out release by the product of Chinese import of drugs registered standard X20000237 and investigate, and compare with Wyeth pharmaceuticals product Efexor XR (Efexor XR).
The release profiles of table 4 embodiment 4
Embodiment 5
The prescription that contains pill core:
Preparation method: with microcrystalline Cellulose and VENLAFAXINE HCL mix homogeneously.Do binding agent with 3% Gonak, use centrifugal granulation to prepare micropill.With material in air dry oven 40 ℃-60 ℃ dry 2-4 hour, sieve, screen out greater than 16 orders and be less than 30 purpose ball cores.
The coating prescription:
Coating operation: get the 30-16 purpose ball core of 500g embodiment 5 preparations, with the method for end spray respectively with sealing coat and controlled release layer coating, the preparation slow-release micro-pill.Coating weightening finish (calculating by polymer weight) 30%.
Release is investigated: carry out release by the product of Chinese import of drugs registered standard X20000237 and investigate, and compare with Wyeth pharmaceuticals product Efexor XR (Efexor XR).
The release profiles of table 5 embodiment 5
Embodiment 6
The prescription that contains pill core:
Preparation method: with microcrystalline Cellulose and VENLAFAXINE HCL mix homogeneously.Do binding agent with the solution that contains Surelease and hydroxypropyl emthylcellulose, use centrifugal granulation to prepare micropill.With material in air dry oven 40 ℃-60 ℃ dry 2-4 hour.Sieve, screen out greater than 16 orders and be less than 30 purpose ball cores.
The coating prescription:
Coating operation: get the 30-16 purpose ball core of 500g embodiment 5 preparations, with the method for end spray respectively with sealing coat and controlled release layer coating, the preparation slow-release micro-pill.Coating weightening finish (calculating by polymer weight) 14%, 20%, 24%, 28%.
Release is investigated: carry out release by the product of Chinese import of drugs registered standard X20000237 and investigate, and compare with Wyeth pharmaceuticals product Efexor XR (Efexor XR).
The release profiles of table 6 embodiment 6
Embodiment 7
The prescription that contains pill core:
Preparation method: with microcrystalline Cellulose and VENLAFAXINE HCL mix homogeneously.Do binding agent with 3% Gonak, use centrifugal granulation to prepare micropill.With material in air dry oven 40 ℃-60 ℃ dry 2-4 hour, sieve, screen out greater than 16 orders and be less than 30 purpose ball cores.
The coating prescription:
Coating operation: get the 30-16 purpose ball core of 500g embodiment 5 preparations, with the method for end spray respectively with sealing coat and controlled release layer coating, the preparation slow-release micro-pill.Coating weightening finish (calculating by polymer weight) 30%.
Release is investigated: carry out release by the product of Chinese import of drugs registered standard X20000237 and investigate, and compare with Wyeth pharmaceuticals product Efexor XR (Efexor XR).
The release profiles of table 7 embodiment 7
Claims (5)
1. venlafaxine hydrochloride sustained-release capsule comprises capsule shells and places the pastille micropill of capsule shells, it is characterized in that described pastille micropill comprises to contain pill core, wrap in and contain the outer sealing coat of pill core and wrap in the outer controlled release layer of sealing coat,
The described pill core that contains is made by the component of following weight percentage ratio:
VENLAFAXINE HCL 30-60%,
Filler 30-80%,
Sustained-release matrix material 1-20%,
Binding agent 1-10%;
The described filler that contains in the pill core is one or more in microcrystalline Cellulose, lactose, the pregelatinized Starch; The sustained-release matrix material is one or more in full-bodied hydroxypropyl emthylcellulose, ethyl cellulose, the acrylic resin; Binding agent is one or more in low viscous hydroxypropyl emthylcellulose, Aquacoat, the acrylic resin aqueous dispersion;
Described sealing coat comprises the full-bodied hydroxypropyl emthylcellulose that weight ratio is 0-10%, to contain pill core weight;
Described controlled release layer comprises the extended release coatings film that weight is 10-50%, in the ground floor coat weight; Described extended release coatings film comprise insoluble polymer 50-70%, to the hole agent be 0-10% and antiplastering aid 20-40%.
2. venlafaxine hydrochloride sustained-release capsule according to claim 1 is characterized in that, described insoluble polymer is one or several in Aquacoat, the acrylic resin aqueous dispersion.
3. venlafaxine hydrochloride sustained-release capsule according to claim 1 is characterized in that, described to the hole agent be in hydroxypropyl emthylcellulose, lactose, sodium chloride, potassium chloride, Polyethylene Glycol, the polyvinylpyrrolidone one or more.
4. venlafaxine hydrochloride sustained-release capsule according to claim 1 is characterized in that, described antiplastering aid is one or more in Pulvis Talci, the glyceryl monostearate.
5. the preparation method of each described venlafaxine hydrochloride sustained-release capsule of claim 1-4, its step is as follows:
1) with behind VENLAFAXINE HCL, filler and the slow release framework material mix homogeneously, use centrifugal granulation or extrude spheronization to prepare micropill, in the micropill preparation process, add binding agent, micropill is dried, sieving obtains containing pill core;
2) will contain pill core and place fluid bed, and adopt the method for end spray to wrap sealing coat and controlled release layer respectively, heat treatment obtains the pastille micropill of VENLAFAXINE HCL;
3) during being incapsulated, the pastille micropill namely gets the venlafaxine hydrochloride sustained-release capsule.
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| Application Number | Priority Date | Filing Date | Title |
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| CN 201310137906 CN103191082A (en) | 2013-04-19 | 2013-04-19 | Venlafaxine hydrochloride spansule and preparation method thereof |
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| CN 201310137906 CN103191082A (en) | 2013-04-19 | 2013-04-19 | Venlafaxine hydrochloride spansule and preparation method thereof |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104739775A (en) * | 2013-12-26 | 2015-07-01 | 广州医药研究总院有限公司 | Novel venlafaxine hydrochloride sustained release pill and preparation method thereof |
| CN105982875A (en) * | 2014-12-27 | 2016-10-05 | 辽宁药联制药有限公司 | Venlafaxine sustained release preparation using waxy material as skeleton and having sustained release effect and preparation method thereof |
| CN106955276A (en) * | 2017-03-28 | 2017-07-18 | 海南合瑞制药股份有限公司 | A kind of venlafaxine hydrochloride slow-release capsule composition |
| CN113041235A (en) * | 2019-12-27 | 2021-06-29 | 西安远大德天药业股份有限公司 | Venlafaxine hydrochloride sustained release preparation, preparation method thereof, venlafaxine hydrochloride sustained release capsule and application thereof |
| CN114288273A (en) * | 2022-02-11 | 2022-04-08 | 桂林华信制药有限公司 | Venlafaxine hydrochloride sustained-release capsule and production process thereof |
-
2013
- 2013-04-19 CN CN 201310137906 patent/CN103191082A/en active Pending
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104739775A (en) * | 2013-12-26 | 2015-07-01 | 广州医药研究总院有限公司 | Novel venlafaxine hydrochloride sustained release pill and preparation method thereof |
| CN105982875A (en) * | 2014-12-27 | 2016-10-05 | 辽宁药联制药有限公司 | Venlafaxine sustained release preparation using waxy material as skeleton and having sustained release effect and preparation method thereof |
| CN106955276A (en) * | 2017-03-28 | 2017-07-18 | 海南合瑞制药股份有限公司 | A kind of venlafaxine hydrochloride slow-release capsule composition |
| CN106955276B (en) * | 2017-03-28 | 2019-12-13 | 海南合瑞制药股份有限公司 | Venlafaxine hydrochloride sustained-release capsule composition |
| CN113041235A (en) * | 2019-12-27 | 2021-06-29 | 西安远大德天药业股份有限公司 | Venlafaxine hydrochloride sustained release preparation, preparation method thereof, venlafaxine hydrochloride sustained release capsule and application thereof |
| CN114288273A (en) * | 2022-02-11 | 2022-04-08 | 桂林华信制药有限公司 | Venlafaxine hydrochloride sustained-release capsule and production process thereof |
| CN114288273B (en) * | 2022-02-11 | 2022-10-18 | 桂林华信制药有限公司 | Venlafaxine hydrochloride sustained-release capsule and production process thereof |
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Application publication date: 20130710 |