CN102772390B - Venlafaxine hydrochloride sustained release capsule and preparation method thereof - Google Patents

Abstract

The invention belongs to the field of pharmaceutical preparations, and discloses a venlafaxine hydrochloride sustained release capsule and a preparation method thereof. The content of the sustained release capsule is a sustained release micro pill, wherein the sustained release pill is successively provided with a pill core, an isolating layer and a sustained release layer from the interior to the exterior, the pill core is prepared from the following constituents according to weight percentage composition: 45-48% of venlafaxine hydrochloride, 15-18% of bulking agent, 3-3.5% of disintegrating agent, 4-6% of povidone K 30, 24-26% of absolute ethyl alcohol and the balance being water; the isolating layer is prepared from the following constituents according to weight percentage composition: 11-13% povidone K30, 83-86% of absolute ethyl alcohol and the balance being talcum powder; the sustained release layer is prepared from the following constituents according to weight percentage composition: 38-42% of ethocel suspension, 0.1-1.0% of polyethylene glycol-60000 and the balance being water, wherein the ethocel accounts for 20-30% of the ethocel suspension in mass; and the preparation method provided by the invention has the following steps of preparing the pill core, packing the isolating layer, packing the sustained release layer and filling a capsule, thus obtaining the sustained release capsule. The venlafaxine hydrochloride sustained release capsule provided by the invention adopts the ethocel, the flammability is low, the hygroscopicity is small, good film formation property can be achieved, the material is stable and is easy to control, and the venlafaxine hydrochloride sustained release capsule is safe and environment-friendly.

Description

A kind of venlafaxine hydrochloride sustained-release capsule and preparation method thereof

Technical field

The invention belongs to technical field of medicine, be specifically related to a kind of venlafaxine hydrochloride sustained-release capsule and preparation method thereof.

Background technology

VENLAFAXINE HCL is a kind of effective antianxiety drugs and antidepressants, and the form with hydrochlorate in medicament exists, its chemical name: (±)-1-[2-(dimethylamino)-1-(4-anisyl) ethyl] the Hexalin hydrochlorate, the chemical structural formula formula is as follows:

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Venlafaxine belongs to the ethylamine derivant, is norepinephrine and serotonin reuptake transporter double inhibitor, always for the first-line treatment of depression, is mainly used in all kinds depression, comprises depression and generalized anxiety disorder with anxiety.

U.S. Wyeth number of patent application: 97109594.9, patent name: slow releasing preparation, wherein use the organic solvents such as dichloromethane.Patent 200910162006.8, patent name: Venlafaxine hydrochloride sustained-release pellet capsules extended release coatings film adopts polyacrylic resin, and this slow-release material price is expensive, and the pharmaceutical production cost is high.

Summary of the invention

For overcoming the deficiencies in the prior art part, the object of the present invention is to provide a kind of venlafaxine hydrochloride sustained-release capsule and preparation method thereof.

For achieving the above object, the technical scheme that the present invention takes is as follows:

A kind of venlafaxine hydrochloride sustained-release capsule, the content of this slow releasing capsule is slow-release micro-pill, this slow-release micro-pill is followed successively by ball core, sealing coat, slow release layer from the inside to the outside, wherein, the ball core is made by the composition of following weight percent: VENLAFAXINE HCL 45-48%, filler 15-18%, disintegrating agent 3-3.5%, PVP K30 4-6%, dehydrated alcohol 24-26%, and surplus is water; Sealing coat is made by the composition of following weight percent: PVP K30 11-13%, dehydrated alcohol 83-86%, and surplus is Pulvis Talci; Slow release layer is made by the composition of following weight percent: ethylcellulose mixed suspension liquid 38-42%, PEG-4000 0.1-1.0%, and surplus is water, the ethyl cellulose mass content of described ethylcellulose mixed suspension liquid is 20-30%.

Described filler is starch, sucrose or both combinations.

Described disintegrating agent is sodium carboxymethyl cellulose.

Preparation method is characterized in that step is as follows:

(1) prepare the ball core: after VENLAFAXINE HCL, filler, disintegrating agent are pulverized respectively, by the recipe quantity mix homogeneously, obtain mixed powder; The PVP K30 of recipe quantity is added in dehydrated alcohol and makes its even expansion, and the limit edged stirs, then adds water and stir, and room temperature is standing to be dissolved it to obtain binding agent fully; Mixed powder adds in pellet processing machine, sprays into the wet ball of binding agent preparation simultaneously, dries, and obtains the ball core;

(2) bag sealing coat: will be after the PVP K30 of recipe quantity, dehydrated alcohol and Pulvis Talci mix homogeneously contagion gown liquid, the ball core of step (1) is carried out to Cotton seeds;

(3) bag slow release layer: will be after the ethylcellulose mixed suspension liquid of recipe quantity, PEG-4000 and water mix homogeneously extended release coatings liquid, the ball core of step (2) is carried out to Cotton seeds, obtain slow-release micro-pill;

(4) filled capsules: the slow-release micro-pill of step (3) is filled in Capsules, obtains slow releasing capsule.

The slow-release material that the present invention adopts is ethyl cellulose, on the one hand in the situation that guarantee the slow release drug effect, avoided the residual of organic solvent to become to produce cost (domestic 380 yuan/kilogram of ethyl cellulose with having reduced, 526/ kilogram of imported from America, polyacrylic resin is mainly used 900/ kilogram of German import); The combustibility of ethyl cellulose is low on the other hand, and hygroscopicity is little, has good film property, and the ethyl cellulose suspension stable material quality of using in production process is easily controlled, and water slurry is safer and environmental protection.

The specific embodiment

Embodiment 1

A kind of venlafaxine sustained-release capsule, the content of this slow releasing capsule is slow-release micro-pill, this slow-release micro-pill is followed successively by ball core, sealing coat, slow release layer from the inside to the outside, ball core, sealing coat, slow release layer prescription as table 1-1, table 1-2, table 1-3.

drug release determination

Get embodiment 1 product, according to drug release determination method (two appendix X D first methods of Chinese Pharmacopoeia version in 2010), adopt the device of dissolution method (two appendix X C first methods of Chinese Pharmacopoeia version in 2010), take water 900ml as release medium, rotating speed is per minute 100 to turn, operation in accordance with the law, in the time of 2,4,8,12,24 hours, get respectively solution 5ml, filter, and the instant water that supplements the uniform temp equal volume in process container, get subsequent filtrate as need testing solution; Another precision takes the VENLAFAXINE HCL reference substance, accurately weighed, makes in every 1ml and approximately contains venlafaxine 70 μ g(specifications with water dissolution quantitative dilution: solution 75mg), product solution in contrast.According to high performance liquid chromatography (two appendix V D of Chinese Pharmacopoeia version in 2010), measure: with octadecylsilane chemically bonded silica, be filler, (get triethylamine 10ml with acetonitrile-triethylamine buffer solution, be diluted with water to 1000ml, with phosphorus acid for adjusting pH to 3.0) (20:80) be mobile phase, the detection wavelength is 225nm, number of theoretical plate calculates and should be not less than 1000 by the venlafaxine peak, and tailing factor should be not more than 2.0.Precision measures test sample liquid and each 20 μ l injection liquid chromatographies of contrast solution, records chromatogram, by external standard method, with calculated by peak area, obtains.Calculate respectively every burst size at different time.Computing formula:

In formula:

A _sample: need testing solution collection of illustrative plates Venlafaxine peak area;

A _right: reference substance solution collection of illustrative plates Venlafaxine peak area;

C _right: reference substance solution concentration;

0.8838: the conversion coefficient of VENLAFAXINE HCL and venlafaxine.

Repeat 6 tests, result of the test is in Table 4, and the burst size of this product in the time of 2,4,8,12,24 hours should be respectively below 30% of corresponding labelled amount, 30%～55%, 55%～80%, more than 65%～90% and 80%, all should be up to specification.

Claims (2)

1. a venlafaxine hydrochloride sustained-release capsule, it is characterized in that: the content of this slow releasing capsule is slow-release micro-pill, this slow-release micro-pill is followed successively by ball core, sealing coat, slow release layer from the inside to the outside, wherein, the ball core is made by the composition of following weight percent: VENLAFAXINE HCL 45-48%, filler 15-18%, disintegrating agent 3-3.5%, PVP K30 4-6%, dehydrated alcohol 24-26%, and surplus is water; Sealing coat is made by the composition of following weight percent: PVP K30 11-13%, dehydrated alcohol 83-86%, and surplus is Pulvis Talci; Slow release layer is made by the composition of following weight percent: ethylcellulose mixed suspension liquid 38-42%, PEG-4000 0.1-1.0%, and surplus is water, the ethyl cellulose mass content of described ethylcellulose mixed suspension liquid is 20-30%; Wherein, described filler is starch, sucrose or both combinations, and described disintegrating agent is sodium carboxymethyl cellulose.

2. a method for preparing venlafaxine hydrochloride sustained-release capsule as claimed in claim 1 is characterized in that step is as follows:

(1) prepare the ball core: after VENLAFAXINE HCL, filler, disintegrating agent are pulverized respectively, by the recipe quantity mix homogeneously, obtain mixed powder; The PVP K30 of recipe quantity is added in dehydrated alcohol and makes its even expansion, and the limit edged stirs, then adds water and stir, and room temperature is standing to be dissolved it to obtain binding agent fully; Mixed powder adds in pellet processing machine, sprays into the wet ball of binding agent preparation simultaneously, dries, and obtains the ball core;

(2) bag sealing coat: will be after the PVP K30 of recipe quantity, dehydrated alcohol and Pulvis Talci mix homogeneously contagion gown liquid, the ball core of step (1) is carried out to Cotton seeds;

(3) bag slow release layer: will be after the ethylcellulose mixed suspension liquid of recipe quantity, PEG-4000 and water mix homogeneously extended release coatings liquid, the ball core of step (2) is carried out to Cotton seeds, obtain slow-release micro-pill;

(4) filled capsules: the slow-release micro-pill of step (3) is filled in Capsules, obtains slow releasing capsule.