CN106955276A - A kind of venlafaxine hydrochloride slow-release capsule composition - Google Patents
A kind of venlafaxine hydrochloride slow-release capsule composition Download PDFInfo
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- CN106955276A CN106955276A CN201710192727.8A CN201710192727A CN106955276A CN 106955276 A CN106955276 A CN 106955276A CN 201710192727 A CN201710192727 A CN 201710192727A CN 106955276 A CN106955276 A CN 106955276A
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- slow
- release
- hydrojet
- venlafaxine hydrochloride
- venlafaxine
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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
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
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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
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4866—Organic macromolecular compounds
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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
- A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
- A61K9/5042—Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
Abstract
The present invention relates to field of medicaments, specifically related to a kind of venlafaxine hydrochloride slow-release capsule composition, the content of the spansule composition is the sustained release pellet being made up of load medicine micropill and slow release layer, carry VENLAFAXINE HCL of the medicine micropill by 58~66 parts by weight, the filler of 75~85 parts by weight, the adhesive composition of 8~12 parts by weight, slow release layer is made up of the Sustained release coating materials of 3.5~6 parts by weight and the pore-foaming agent of 18~27 parts by weight, and wherein the quality of slow release layer is the 14~17% of drug-loaded layer quality.Present invention also offers the preparation method of venlafaxine hydrochloride slow-release capsule composition, make load medicine micropill using fluid bed and carry out the obtained sustained release pellet of slow release layer coating.Venlafaxine hydrochloride slow-release capsule composition produced by the present invention can meet manufacturing condition without the auxiliary materials such as antiplastering aid, plasticizer, regulation fluidized-bed process, obtain grinding the close medicine of drug effect fruit with former, save cost, reduce technology difficulty.
Description
Technical field
The present invention relates to field of medicaments, specifically, it is related to a kind of venlafaxine hydrochloride slow-release capsule composition.
Background technology
Venlafaxine is a kind of brand-new antidepressants.Chemical name is (R/S) -1- [2- (dimethylamine) -1- (4- methoxies
Phenyl) ethyl] cyclohexanol, Venlafaxine is that its neurotransmitter is lived in enhancing central nervous system to the antidepression mechanism of human body
Property.Preclinical study shows that Venlafaxine and its major metabolite O-DMV (ODV) are serotonins and go first
The potent inhibitor of adrenaline reuptake.Intake of the Venlafaxine to dopamine also has slight inhibitory action.Zooscopy shows
Show only after tricyclic antidepressant is given for a long time, it is possible to decrease the reactivity of beta-adrenergic.However, single or long-term taking
After Venlafaxine, Venlafaxine and O-DMV can reduce the reactivity of beta-adrenergic.Venlafaxine and
O-DMV is similar to the inhibitory action of neurotransmitter re-uptake.
VENLAFAXINE HCL is a kind of novel antidepressant, with instant effect, better tolerance, in short term and long-term treatment effects
All good distinguishing feature, but there is half-life short (about 5 ± 2 hours), patient and need frequent drug administration in the Venlafaxine of ordinary preparation
(2~3 times/day), and side effect it is larger the problems such as.After the Venlafaxine conventional tablet of therapeutic dose is taken, medicine can be rapid
Dissolving, causes the blood concentration of active principle venlafaxine soon after administration to raise rapidly, reactive compound quilt after several hours
It is metabolized or drains, blood concentration declines rapidly, about 12 hours after administration, blood concentration, which has dropped to, is not enough to play treatment work
Level, it is therefore desirable to multiple dosing, after daily multiple dosing, most commonly seen side effect is exactly nausea, it is demonstrated experimentally that
Nausea occurs for the patient treated with Venlafaxine, about 45% patient, and about 17% patient even vomits.
Therefore there are many venlafaxine hydrochloride slow-release capsule (trade names set up and produced in Wyeth of the U.S.：" happy promise
Think ") on the basis of the sustained release of VENLAFAXINE HCL is studied, the Chinese patent of Application No. 201210583848.2 is related to one kind
Venlafaxine hydrochloride slow-release capsule, spansule content prepared by the invention is sustained release pellet, and the micropill composition is as follows：1)
Pellet core, is made up of the component of following weight/mass percentage composition：VENLAFAXINE HCL 28-45%, HPMC 0.5-
1.5%, microcrystalline cellulose 53.5-71.5%；2) clothing film is sustained, is made up of the component of following weight/mass percentage composition：
KollicoatSR30D 63-70% in terms of solid masses, talcum powder 22.5-31%, triethyl citrate 6-7.5%；Wherein wrap
Clothing quality is the 10~20% of capsule core.Venlafaxine hydrochloride slow-release capsule drug release prepared by the invention is steady, and organic solvent-free is residual
Problem is stayed, product takes safety, and production environment is friendly.But the sustained release pellet provided in the invention is provided and has used talcum
Powder easily causes " stifled rifle " phenomenon during fluid bed medicine-feeding, causes hydrojet not smooth, have impact on technological process as antiplastering aid
With the quality of medicine；Simultaneously according to Shen Ruifang document (antiplastering aid talcum powder pairNE 30D feature release-controlled films
Influence research,《He'nan University》, 2015) understand, coating micro-pill water absorption rate and weight-loss ratio experiment and the experiment of vitro release card
Bright, with the increase of amount of talc, membrane permeability increase, coating micro-pill water absorption increase, medicine dissolving is accelerated, and causes medicine
Release is accelerated, and micropill weight-loss ratio is accelerated.The slow release effect of medicine is caused to be unable to reach preferable state.
It is micro- that the Chinese patent of Application No. 20131060744.9 provides a kind of venlafaxine hydrochloride sustained-release for being resistant to alcohol
The preparation method of ball, the sustained release pellet is made up of VENLAFAXINE HCL pellet core, barrier gown layer and sustained-release coating layer, wherein slow
It is interpreted into membrane material and is selected from the mixing coating material that ethyl cellulose and polysaccharide are constituted, pore-foaming agent is selected from Hydroxypropyl methylcellulose, gathered
One or more of mixing in ethylene glycol, polyvinyl alcohol, KollicoatIR；Plasticizer is selected from triethyl citrate, SA two
One or more of mixing in butyl ester, diethyl phthalate；Antiplastering aid is in talcum powder, silica, magnesium stearate
One or more of mixing.Although plasticizer can play a part of adhesion between reduction micropill, if consumption controls bad, meeting
Cause high molecular polymer to overbate, equally cause adhesion.
In view of this, it is special to propose the present invention.
The content of the invention
The present invention is intended to provide a kind of venlafaxine hydrochloride sustained-release glue that to grind medicine release with VENLAFAXINE HCL original close
Capsule composition, by fluidized-bed process carry preparation and the coating of slow release layer of medicine micropill, without using antiplastering aid, plasticizer etc.
Auxiliary material, reach to original grind medicine slow release effect it is similar on the basis of, saving cost simultaneously reduces the purpose of technology difficulty.
To achieve the above object, the present invention is specifically adopted the following technical scheme that：
A kind of venlafaxine hydrochloride slow-release capsule composition, the content of the spansule composition is by load medicine micropill
The sustained release pellet constituted with slow release layer,
The load medicine micropill is made up of the composition of following parts by weight：
58~66 parts of VENLAFAXINE HCL
75~85 parts of filler
8~12 parts of adhesive
The slow release layer is made up of the composition of following parts by weight：
3.5~6 parts of pore-foaming agent
18~27 parts of Sustained release coating materials
The quality of the slow release layer is the 14~17% of drug-loaded layer quality.
The action principle of antiplastering aid is that insoluble composition is with the addition of in high molecular polymer, reduces the energy of film formation
Power, electric Microscopic observation, the ethyl cellulose surface containing antiplastering aid becomes coarse, compared with the prescription for being added without antiplastering aid,
Prescription containing antiplastering aid causes drug releasing rate to be accelerated.When plasticizer is added in high molecular polymer, high score will be penetrated into
Between subchain, reduce intermolecular or intramolecular active force, high molecular network structure is become loose, it is easy to film forming.Coating of pellets
When, suitable plasticizer can also play a part of adhesion between reduction micropill.But too increase the consumption of plasticizer, it can cause
High molecular polymer is overbated, and equally causes adhesion.
Therefore the invention provides a kind of Wen La for not containing antiplastering aid and plasticizer in medicine micropill and slow release layer is carried
The pungent sustained release pellet of method, will not influence the slow release effect of medicine because of the presence of above two auxiliary material.
The present invention further scheme be：The quality of the slow release layer is the 16% of drug-loaded layer quality.
When understanding slow release layer for carrying the weightening of medicine micropill in the range of 14%~17% through correlative study of the present invention work,
Self-control protracted release drug and original grind that medicine listing product release behavior is consistent, and 16% releasing effect of slow release layer weightening is optimal knowable to analysis.
The present invention further scheme be：In the slow release layer mass ratio of pore-foaming agent and Sustained release coating materials be 1.3~
3.2:10, preferred mass ratio is 2.22:10.
Present invention concern VENLAFAXINE HCL releasing effect, in the research process of the present invention, staff has found to work as and adjusted
When saving the coating material of slow release layer and the weight of pore-foaming agent for certain proportion, the releasing effect of capsule is the most similar to listing product,
Selection checking releasing effect is first carried out to the coating material of different component and pore-foaming agent, choose effect preferably ethyl cellulose and
HPMC E50 carry out Different Weight than releasing effect test, learn the optimal of pore-foaming agent and Sustained release coating materials
Weight ratio is 2.22:10.
The present invention further scheme be：The Sustained release coating materials are selected from makrolon, vinylacetate, hydroxypropyl
One kind in cellulose, ethyl cellulose, Sustained release coating materials are preferably ethyl cellulose.
The present invention further scheme be：The pore-foaming agent is selected from sodium chloride, potassium chloride, HPMC E50, poly-
One kind in vinylpyrrolidone, pore-foaming agent is preferably HPMC E50.
The pore-foaming agent in slow release layer and Sustained release coating materials are selected in such scheme, the application staff's warp
A large amount of creative works are crossed, the optimal proportion and most optimum materials for having obtained pore-foaming agent and Sustained release coating materials are selected, Ke Yida
Medicine extremely similar releasing effect is ground to former.
The present invention further scheme be：Described adhesive is selected from acrylic resin, HPMC, ethyl cellulose
One kind in element, adhesive is preferably HPMC.
In such scheme, HPMC is the HPMC product with low viscosity and low molecule amount,
It can realize while polymer solution concentration is increased, the viscosity of solution not dramatically increased.
The present invention further scheme be：The filler is one kind in sucrose, microcrystalline cellulose, starch, lactose, is filled out
Fill agent preferably microcrystalline cellulose.
Present invention also offers a kind of preparation method of venlafaxine hydrochloride slow-release capsule composition, comprise the following steps：
(1) by VENLAFAXINE HCL dissolving be slowly added to afterwards in ethanol adhesive stir and sieve obtain carry medicine medicine
Liquid；
(2) hydrojet is carried out to the surface of filler using drug-loaded layer decoction made from step (1) and the obtained load medicine that sieves is micro-
Ball；
(3) pore-foaming agent is added to the water into addition ethanol after stirring to be again stirring for uniformly, adding Sustained release coating materials stirring
Uniformly obtain slow release layer decoction；
(4) hydrojet and mistake are carried out using the medicine micropill surface that carries obtained to step (2) of slow release layer decoction made from step (3)
Sieve obtains sustained release pellet；
(5) sustained release pellet made from step (4) is loaded into capsule and obtains finished product；
According to above-mentioned preparation method, its preferred preparation process is as follows：
(1) recipe quantity ethanol is weighed, is placed in the container of cleaning, recipe quantity VENLAFAXINE HCL is added, is stirred to dissolve
Uniformly, recipe quantity adhesive is slow added into, strong stirring makes to be uniformly dispersed, crosses 100 mesh sieves, obtain drug-loaded layer decoction；
(2) filler is placed in fluid bed, sets intake air temperature, setpoint frequency after drying 30 minutes, sets certain
Atomizing pressure, nozzle needle pressure, regulation guide shell highly, makes filler fluidisation uniform, begins to use step after control material temperature
Suddenly drug-loaded layer decoction made from (1) carries out hydrojet to filler, control material temperature during hydrojet and after end, is further continued for
Dry 30 minutes, rear bearing medicine micropill will be dried and cross 16 mesh sieves, 40 sieves respectively, the load medicine micropill between 16~40 mesh is taken, it is standby；
(3) purified water (temperature is 80~100 DEG C) is weighed by recipe quantity, is slowly added to the pore-foaming agent of recipe quantity, side edged
Stirring, makes to be uniformly dispersed.Recipe quantity ethanol is added, after stirring, the Sustained release coating materials of recipe quantity is slowly added to, strongly stirs
Mix and be uniformly dispersed, obtain slow release layer decoction；
(4) medicine micropill will be carried to be placed in fluid bed, and will set intake air temperature, setpoint frequency after drying 30 minutes, sets one
Fixed atomizing pressure, nozzle needle pressure, regulation guide shell highly, make load medicine micropill fluidisation uniform, start to make after control material temperature
Hydrojet is carried out to carrying medicine micropill with slow release layer decoction made from step (3), control material temperature during hydrojet and after end,
It is further continued for drying 30 minutes, sustained release pellet after drying is crossed into 16 mesh sieves, 24 mesh sieves respectively, takes the load medicine between 16~24 mesh micro-
Ball, is filled in capsule, obtains venlafaxine hydrochloride slow-release capsule.
Wherein, the frequency of hydrojet described in step (2) and step (4) is 2~8Hz, and is realized using fluid bed.
Original grinds product preparation technology and is made spherical piller for extrusion spheronization method, and VENLAFAXINE HCL light weight, poor fluidity,
Account for large percentage in prescription, relevant staff of the invention two kinds of techniques of adding medicine to centrifugal granulating and micropill have been carried out pair
Than the inadequate rounding of pill as a result prepared by discovery centrifugal granulating, pill density are less than normal, and capsule filling machine track fails what is reached
Maximum loading amount is less than theoretical grain weight, and prepared pill can not meet capsule filling requirement, therefore finally determine to take micropill to fluidize
Bed medicine-feeding method technique.
And due to no use antiplastering aid and plasticizer, therefore reduce hydrojet frequency and at utmost reduce the adhesion of micropill
Phenomenon.
The present invention further scheme be：The original frequency of the hydrojet is 2~6Hz, and preferably original frequency is 3Hz.
The present invention further scheme be：Temperature of charge in the step (2) and step (4) before hydrojet is 35~45
DEG C, the temperature of charge in hydrojet is 30~45 DEG C, and the temperature of charge after hydrojet is 35~50 DEG C.
The present invention further scheme be：The intake air temperature of the fluid bed is 33~55 DEG C.
Guide shell is the core of fluidized bed coating, is the key position that material is contacted with coating solution here, if air inlet temperature
Atomization drying can be caused by spending height, and coating effect is undesirable, and intake air temperature is too low can cause the not smooth even material knot of fluidisation
Block；And the moisture evaporation deficiency of the too low decoction drop of temperature of charge also results in adhesion.Therefore selection intake air temperature is slightly above
Temperature of charge, and totally maintain at a lower temperature, above mentioned problem can be overcome.
Beneficial effects of the present invention are：
1. prevented in the venlafaxine hydrochloride slow-release capsule composition that the present invention is provided without addition antiplastering aid and plasticizer
Antiplastering aid influences the slow release effect of medicine, it also avoid the adhesion phenomenon that plasticizer is likely to result in；
2. the venlafaxine hydrochloride slow-release capsule composition that the present invention is provided is with former medicine phases of grinding than with approximate release effect
Really, the side effects of pharmaceutical drugs can be reduced；
3. the preparation method for the venlafaxine hydrochloride slow-release capsule composition that the present invention is provided will not because of auxiliary material addition
Complicated parameter adjustment is carried out, simply and stably.
Brief description of the drawings
Fig. 1 in the present invention with Different Weight than the slow release layer that constitutes of ethyl cellulose and HPMC E50
The release profiles that medicine lists product slow release layer are ground with former.
Fig. 2 is the different weightening slow release layers of the present invention and the former release profiles for grinding medicine listing product slow release layer weightening.
Fig. 3 is 75mg specifications embodiment 1 of the present invention and the former release profiles for grinding medicine listing product in water.
Fig. 4 is 75mg specifications embodiment 1 of the present invention and the former release profiles for grinding medicine listing product in pH1.0 hydrochloric acid.
Fig. 5 is that 75mg specifications embodiment 1 of the present invention and the former release for grinding medicine listing product in pH4.5 acetate buffers are bent
Line.
Fig. 6 is that 75mg specifications embodiment 1 of the present invention and the former release for grinding medicine listing product in pH6.8 phosphate buffers are bent
Line.
Fig. 7 is 150mg specifications embodiment 2 of the present invention and the former release profiles for grinding medicine listing product in water.
Fig. 8 is 150mg specifications embodiment 2 of the present invention and the former release profiles for grinding medicine listing product in pH1.0 hydrochloric acid.
Fig. 9 is 150mg specifications embodiment 2 of the present invention and the former release for grinding medicine listing product in pH4.5 acetate buffers
Curve.
Figure 10 is 150mg specifications embodiment 2 of the present invention and the former release for grinding medicine listing product in pH6.8 phosphate buffers
Curve.
Embodiment
Be below the embodiment of the present invention, described embodiment be in order to further describe the present invention, rather than
The limitation present invention.
Selection first to the slow release layer of the VENLAFAXINE HCL micropill of the present invention carries out prescription screening experiment, wherein pore
The weight ratio of agent and Sustained release coating materials is 1.6:10, from the pore-foaming agent and Sustained release coating materials of different materials, such as the institute of table 1
Show, selection, which is fixed into load sharing medicine micropill and is coated, obtains own product, and the releasing effect of own product and original are ground into medicine (" happy promise
Think ") it is compared and calculates burst size, the computing formula of burst size is as follows：
Note：At：The peak area of need testing solution Venlafaxine；
As：The peak area of reference substance solution Venlafaxine；
Wt：Test sample sample weighting amount, mg；
Dt：Test sample extension rate；
P：Venlafaxine reference substance content；
Cs：Venlafaxine reference substance solution concentration.
(1500, specification are made in the VENLAFAXINE HCL prescription screening table of table 1：75mg)
Table 1 understands that the releasing effect of own product 9 and listing product are closest.Therefore selection ethyl cellulose is used as sustained release coating
Material, selection HPMC E50 is used as pore-foaming agent.
Further to ethyl cellulose and HPMC E50 weight than selecting, the part by weight such as institute of table 2
Show, to grind the corresponding release profiles of medicine listing product as shown in Figure 1 for each scheme and original in table 2.
The slow release layer ethyl cellulose of table 2 and HPMC E50 part by weight selection schemes
From Fig. 1 and table 2, when the ethyl cellulose and HPMC E50 mass ratios using scheme 3, its
Release and listing product effect are closest, therefore pore-foaming agent HPMC E50 and Sustained release coating materials ethyl cellulose
The optimum quality ratio of element is 2.22:10.
The slow release layer of the VENLAFAXINE HCL micropill of the present invention is selected relative to the weightening for carrying medicine micropill again, respectively
Choose original and grind product, weightening 12%, 14%, 16%, 17%, 20% sustained release pellet carries out release test, test result such as table 3
Shown, the release profiles comparison diagram of difference weightening is as shown in Figure 2.
The layer weightening selection of the venlafaxine hydrochloride sustained-release of table 3
Understood by table 3 and Fig. 2 in the range of the actual weightening 14%~17% of slow release layer, own product and listing product release behavior
Unanimously, but analyzed from data, slow release layer 16% releasing effect of weightening is optimal.
Embodiment 1
According to above-mentioned the selection result, determine to use prescription (specification as follows：75mg) carry out spansule composition
Preparation：
Preparation method is as follows：
(1) 6660g ethanol is weighed, is placed in the container of cleaning, 1273g VENLAFAXINE HCLs are added, is stirred to dissolve
It is even, 225g Hydroxypropyl methylcelluloses are slow added into, strong stirring makes to be uniformly dispersed, cross 100 mesh sieves, obtain drug-loaded layer decoction；
(2) 1650g microcrystalline cellulose pellets capsule cores are placed in fluid bed, set intake air temperature as 39 DEG C, setting frequency
Rate, after drying 30 minutes, sets certain atomizing pressure, nozzle needle pressure, regulation guide shell highly, makes microcrystalline cellulose pellets ball
Core fluidisation is uniform, and control material temperature is to begin to use drug-loaded layer decoction made from step (1) to microcrystalline cellulose after 33~37 DEG C
Plain fine pellet core carries out hydrojet, and hydrojet frequency is initially set to 3Hz, and control hydrojet frequency must not exceed during 8Hz, hydrojet,
Temperature of charge is controlled between 33~37 DEG C.After hydrojet terminates, by temperature of charge control to 37 DEG C~41 DEG C, it is further continued for drying 30
Minute, rear bearing medicine micropill will be dried and cross 16 mesh sieves, 40 sieves respectively, the load medicine micropill between 16~40 mesh is taken, it is standby；
(3) purified water 921g (temperature is 80~100 DEG C) is weighed, 90g Hydroxypropyl methylcellulose E50, side edged is slowly added to
Stirring, makes to be uniformly dispersed.7831g ethanol is added, after stirring, 405g ethyl celluloses, strong stirring point is slowly added to
Dissipate uniform, obtain slow release layer decoction；
(4) medicine micropill will be carried to be placed in fluid bed, sets intake air temperature as 37 DEG C, setpoint frequency, after drying 30 minutes,
The certain atomizing pressure of setting, nozzle needle pressure, regulation guide shell highly, make load medicine micropill fluidisation uniformly, control material temperature is
Slow release layer decoction made from step (3) is begun to use to carry out hydrojet to carrying medicine micropill after 35~40 DEG C, hydrojet frequency is initially set up
For 3Hz, control hydrojet frequency be must not exceed during 8Hz, hydrojet, and temperature of charge is controlled between 31~36 DEG C.Hydrojet terminates
Afterwards, by temperature of charge control to 35 DEG C~40 DEG C, be further continued for dry 30 minutes, by sustained release pellet after drying respectively cross 16 mesh sieves,
24 mesh sieves, take the load medicine micropill between 16~24 mesh, are filled in capsule, obtain venlafaxine hydrochloride slow-release capsule, numbering is
130201A。
Respectively to own product 130201A (specifications：75mg) in water, in pH1.0 hydrochloric acid, in pH4.5 acetate buffers
With the release in pH6.8 phosphate buffers calculate obtaining release profiles, as illustrated in figures 3-6.
Embodiment 2
According to above-mentioned the selection result, determine to use prescription (specification as follows：150mg) carry out spansule composition
Preparation：
Preparation method is as follows：
(1) 6660g ethanol is weighed, is placed in the container of cleaning, 1273g VENLAFAXINE HCLs are added, is stirred to dissolve
It is even, 225g Hydroxypropyl methylcelluloses are slow added into, strong stirring makes to be uniformly dispersed, cross 100 mesh sieves, obtain drug-loaded layer decoction；
(2) 1650g microcrystalline cellulose pellets capsule cores are placed in fluid bed, set intake air temperature as 39 DEG C, setting frequency
Rate, after drying 30 minutes, sets certain atomizing pressure, nozzle needle pressure, regulation guide shell highly, makes microcrystalline cellulose pellets ball
Core fluidisation is uniform, and control material temperature is to begin to use drug-loaded layer decoction made from step (1) to microcrystalline cellulose after 33~37 DEG C
Plain fine pellet core carries out hydrojet, and hydrojet frequency is initially set to 4Hz, and control hydrojet frequency must not exceed during 8Hz, hydrojet,
Temperature of charge is controlled between 33~37 DEG C.After hydrojet terminates, by temperature of charge control to 37 DEG C~41 DEG C, it is further continued for drying 30
Minute, rear bearing medicine micropill will be dried and cross 16 mesh sieves, 40 sieves respectively, the load medicine micropill between 16~40 mesh is taken, it is standby；
(3) purified water 1313g (temperature is 80~100 DEG C) is weighed, 91g Hydroxypropyl methylcellulose E50, side edged is slowly added to
Stirring, makes to be uniformly dispersed.7439g ethanol is added, after stirring, 407g ethyl celluloses, strong stirring point is slowly added to
Dissipate uniform, obtain slow release layer decoction；
(4) medicine micropill will be carried to be placed in fluid bed, sets intake air temperature as 37 DEG C, setpoint frequency, after drying 30 minutes,
The certain atomizing pressure of setting, nozzle needle pressure, regulation guide shell highly, make load medicine micropill fluidisation uniformly, control material temperature is
Slow release layer decoction made from step (3) is begun to use to carry out hydrojet to carrying medicine micropill after 35~40 DEG C, hydrojet frequency is initially set up
For 3Hz, control hydrojet frequency be must not exceed during 8Hz, hydrojet, and temperature of charge is controlled between 31~36 DEG C.Hydrojet terminates
Afterwards, by temperature of charge control to 35 DEG C~40 DEG C, be further continued for dry 30 minutes, by sustained release pellet after drying respectively cross 16 mesh sieves,
24 mesh sieves, take the load medicine micropill between 16~24 mesh, are filled in capsule, obtain venlafaxine hydrochloride slow-release capsule, numbering is
130201B。
Respectively to own product 130201B (specifications：150mg) in water, in pH1.0 hydrochloric acid, in pH4.5 acetate buffers
With the release in pH6.8 phosphate buffers calculate obtaining release profiles, as shown in Fig. 7~10.
Embodiment 3
According to above-mentioned the selection result, determine to use prescription (specification as follows：75mg) carry out spansule composition
Preparation：
Preparation method is as follows：
(1) 9300g ethanol is weighed, is placed in the container of cleaning, 1867g VENLAFAXINE HCLs are added, is stirred to dissolve
It is even, 320g Hydroxypropyl methylcelluloses are slow added into, strong stirring makes to be uniformly dispersed, cross 100 mesh sieves, obtain drug-loaded layer decoction；
(2) 2337g microcrystalline cellulose pellets capsule cores are placed in fluid bed, set intake air temperature as 39 DEG C, setting frequency
Rate, after drying 30 minutes, sets certain atomizing pressure, nozzle needle pressure, regulation guide shell highly, makes microcrystalline cellulose pellets ball
Core fluidisation is uniform, and control material temperature is to begin to use drug-loaded layer decoction made from step (1) to microcrystalline cellulose after 33~37 DEG C
Plain fine pellet core carries out hydrojet, and hydrojet frequency is initially set to 3Hz, and control hydrojet frequency must not exceed during 8Hz, hydrojet,
Temperature of charge is controlled between 33~37 DEG C.After hydrojet terminates, by temperature of charge control to 37 DEG C~41 DEG C, it is further continued for drying 30
Minute, rear bearing medicine micropill will be dried and cross 16 mesh sieves, 40 sieves respectively, the load medicine micropill between 16~40 mesh is taken, it is standby；
(3) purified water 1284g (temperature is 80~100 DEG C) is weighed, 85g Hydroxypropyl methylcellulose E50, side edged is slowly added to
Stirring, makes to be uniformly dispersed.7275g ethanol is added, after stirring, 637g ethyl celluloses, strong stirring point is slowly added to
Dissipate uniform, obtain slow release layer decoction；
(4) medicine micropill will be carried to be placed in fluid bed, sets intake air temperature as 37 DEG C, setpoint frequency, after drying 30 minutes,
The certain atomizing pressure of setting, nozzle needle pressure, regulation guide shell highly, make load medicine micropill fluidisation uniformly, control material temperature is
Slow release layer decoction made from step (3) is begun to use to carry out hydrojet to carrying medicine micropill after 35~40 DEG C, hydrojet frequency is initially set up
For 3Hz, control hydrojet frequency be must not exceed during 8Hz, hydrojet, and temperature of charge is controlled between 31~36 DEG C.Hydrojet terminates
Afterwards, by temperature of charge control to 35 DEG C~40 DEG C, be further continued for dry 30 minutes, by sustained release pellet after drying respectively cross 16 mesh sieves,
24 mesh sieves, take the load medicine micropill between 16~24 mesh, are filled in capsule, obtain venlafaxine hydrochloride slow-release capsule, numbering is
130202A。
Embodiment 4
According to above-mentioned the selection result, determine to use prescription (specification as follows：150mg) carry out spansule composition
Preparation：
Preparation method is as follows：
(1) 3980g ethanol is weighed, is placed in the container of cleaning, 764g VENLAFAXINE HCLs are added, is stirred to dissolve
It is even, 122g Hydroxypropyl methylcelluloses are slow added into, strong stirring makes to be uniformly dispersed, cross 100 mesh sieves, obtain drug-loaded layer decoction；
(2) 1032g microcrystalline cellulose pellets capsule cores are placed in fluid bed, set intake air temperature as 39 DEG C, setting frequency
Rate, after drying 30 minutes, sets certain atomizing pressure, nozzle needle pressure, regulation guide shell highly, makes microcrystalline cellulose pellets ball
Core fluidisation is uniform, and control material temperature is to begin to use drug-loaded layer decoction made from step (1) to microcrystalline cellulose after 33~37 DEG C
Plain fine pellet core carries out hydrojet, and hydrojet frequency is initially set to 4Hz, and control hydrojet frequency must not exceed during 8Hz, hydrojet,
Temperature of charge is controlled between 33~37 DEG C.After hydrojet terminates, by temperature of charge control to 37 DEG C~41 DEG C, it is further continued for drying 30
Minute, rear bearing medicine micropill will be dried and cross 16 mesh sieves, 40 sieves respectively, the load medicine micropill between 16~40 mesh is taken, it is standby；
(3) purified water 441g (temperature is 80~100 DEG C) is weighed, 62g Hydroxypropyl methylcellulose E50, side edged is slowly added to
Stirring, makes to be uniformly dispersed.4053g ethanol is added, after stirring, 243g ethyl celluloses, strong stirring point is slowly added to
Dissipate uniform, obtain slow release layer decoction；
(4) medicine micropill will be carried to be placed in fluid bed, sets intake air temperature as 37 DEG C, setpoint frequency, after drying 30 minutes,
The certain atomizing pressure of setting, nozzle needle pressure, regulation guide shell highly, make load medicine micropill fluidisation uniformly, control material temperature is
Slow release layer decoction made from step (3) is begun to use to carry out hydrojet to carrying medicine micropill after 35~40 DEG C, hydrojet frequency is initially set up
For 3Hz, control hydrojet frequency be must not exceed during 8Hz, hydrojet, and temperature of charge is controlled between 31~36 DEG C.Hydrojet terminates
Afterwards, by temperature of charge control to 35 DEG C~40 DEG C, be further continued for dry 30 minutes, by sustained release pellet after drying respectively cross 16 mesh sieves,
24 mesh sieves, take the load medicine micropill between 16~24 mesh, are filled in capsule, obtain venlafaxine hydrochloride slow-release capsule, numbering is
130202B。
Comparative example 1
On the basis of the prescription and preparation method of embodiment 1, added simultaneously with adhesive in (1) the step of preparation method
Account for and carry talcum powder of the medicine micropill solid content percentage by weight for 5~10wt% as antiplastering aid, the step of preparation method in (3)
Triethyl citrate of the slow release layer solid content percentage by weight for 10~15wt% is accounted for as plasticizer with adding, obtained finished product
The rate of release of middle VENLAFAXINE HCL is faster than the former medicine that grinds and lists the finished product that product and numbering are 130201A, to find out its cause, being due to
Antiplastering aid contains antiplastering aid as the ability that polymer membrane formation is reduced in insoluble composition, electric Microscopic observation
Ethyl cellulose surface becomes coarse, compared with the prescription for being added without antiplastering aid, and the prescription containing antiplastering aid causes insoluble drug release
Speed is accelerated；And plasticizer will be penetrated between macromolecular chain when being added in high molecular polymer, reduce intermolecular or intramolecular
Active force, makes high molecular network structure become loose, and high molecular polymer can be caused to overbate, do not reach preferable release
Effect.And antiplastering aid is not contained in the load medicine micropill that provides of the present invention and slow release layer and the venlafaxine sustained-release of plasticizer is micro-
Ball, will not influence the slow release effect of medicine because of the presence of above two auxiliary material.
Above-mentioned experiment has also been carried out to the venlafaxine hydrochloride slow-release capsule composition prepared by other embodiments of the present invention,
The result that it is obtained is similar.
The present invention is described in detail above, its object is to allow those of ordinary skill in the art to understand this
The content of invention is simultaneously carried out, and it is not intended to limit the scope of the present invention, all Spirit Essence institutes according to the present invention
The equivalent change or modification done, should all cover within the scope of the present invention.
Claims (10)
1. a kind of venlafaxine hydrochloride slow-release capsule composition, it is characterised in that the content of the spansule composition is
The sustained release pellet being made up of load medicine micropill and slow release layer,
The load medicine micropill is made up of the composition of following parts by weight：
58~66 parts of VENLAFAXINE HCL
75~85 parts of filler
8~12 parts of adhesive
The slow release layer is made up of the composition of following parts by weight：
3.5~6 parts of pore-foaming agent
18~27 parts of Sustained release coating materials
The quality of the slow release layer is the 14~17% of drug-loaded layer quality.
2. venlafaxine hydrochloride slow-release capsule composition according to claim 1, it is characterised in that the matter of the slow release layer
Measure as the 16% of drug-loaded layer quality.
3. venlafaxine hydrochloride slow-release capsule composition according to claim 1 or 2, it is characterised in that the slow release layer
The mass ratio of middle pore-foaming agent and Sustained release coating materials is 1.3~3.2:10, preferred mass ratio is 2.22:10.
4. the venlafaxine hydrochloride slow-release capsule composition according to claims 1 to 3 any one, it is characterised in that
The Sustained release coating materials in makrolon, vinylacetate, HPMC, ethyl cellulose one
Kind, Sustained release coating materials are preferably ethyl cellulose；
The one kind of the pore-foaming agent in sodium chloride, potassium chloride, HPMC E50, polyvinylpyrrolidone, pore
Agent is preferably HPMC E50.
5. the venlafaxine hydrochloride slow-release capsule composition according to Claims 1 to 4 any one, it is characterised in that institute
The one kind of adhesive in acrylic resin, HPMC, ethyl cellulose is stated, adhesive is preferably hydroxypropyl
Cellulose.
6. the venlafaxine hydrochloride slow-release capsule composition according to Claims 1 to 5 any one, it is characterised in that institute
It is one kind in sucrose, microcrystalline cellulose, starch, lactose to state filler, and filler is preferably microcrystalline cellulose.
7. a kind of preparation method of venlafaxine hydrochloride slow-release capsule composition as described in claim 1~6 any one, bag
Include following steps：
(1) by VENLAFAXINE HCL dissolving be slowly added to afterwards in ethanol adhesive stir and sieve obtain carry medicine decoction；
(2) carry out hydrojet to the surface of filler using drug-loaded layer decoction made from step (1) and sieve to be made to carry medicine micropill；
(3) pore-foaming agent is added to the water into addition ethanol after stirring to be again stirring for uniformly, adding Sustained release coating materials and stirring
Obtain slow release layer decoction；
(4) hydrojet is carried out to the obtained load medicine micropill surface of step (2) using slow release layer decoction made from step (3) and sieved
To sustained release pellet；
(5) sustained release pellet made from step (4) is loaded into capsule and obtains finished product；
Characterized in that, the frequency of hydrojet described in step (2) and step (4) is 2~8Hz, and realized using fluid bed
's.
8. the preparation method of venlafaxine hydrochloride slow-release capsule composition according to claim 7, it is characterised in that described
The original frequency of hydrojet is 2~6Hz, and preferably original frequency is 3Hz.
9. the preparation method of the venlafaxine hydrochloride slow-release capsule composition according to claim 7 or 8, it is characterised in that
Temperature of charge in the step (2) and step (4) before hydrojet is 35~45 DEG C, and the temperature of charge in hydrojet is 30~45 DEG C,
Temperature of charge after hydrojet is 35~50 DEG C.
10. the preparation method of the venlafaxine hydrochloride slow-release capsule composition according to claim 7~9 any one, its
It is characterised by, the intake air temperature of the fluid bed is 33~55 DEG C.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN112402395A (en) * | 2020-10-28 | 2021-02-26 | 海南卫康制药(潜山)有限公司 | Venlafaxine sustained-release capsule composition and preparation process thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103054835A (en) * | 2013-01-30 | 2013-04-24 | 张晓明 | Venlafaxine sustained-release capsule and preparation process thereof |
| CN103191082A (en) * | 2013-04-19 | 2013-07-10 | 浙江美华鼎昌医药科技有限公司 | Venlafaxine hydrochloride spansule and preparation method thereof |
| CN103751151A (en) * | 2013-12-31 | 2014-04-30 | 北京万全德众医药生物技术有限公司 | Venlafaxine slow-release formulation capable of providing 24-h release result and preparation method of venlafaxine slow-release formulation |
| CN103919731A (en) * | 2013-11-29 | 2014-07-16 | 山东省医药工业研究所 | Preparation of alcohol tolerant venlafaxine hydrochloride sustained-release pellet |
-
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103054835A (en) * | 2013-01-30 | 2013-04-24 | 张晓明 | Venlafaxine sustained-release capsule and preparation process thereof |
| CN103191082A (en) * | 2013-04-19 | 2013-07-10 | 浙江美华鼎昌医药科技有限公司 | Venlafaxine hydrochloride spansule and preparation method thereof |
| CN103919731A (en) * | 2013-11-29 | 2014-07-16 | 山东省医药工业研究所 | Preparation of alcohol tolerant venlafaxine hydrochloride sustained-release pellet |
| CN103751151A (en) * | 2013-12-31 | 2014-04-30 | 北京万全德众医药生物技术有限公司 | Venlafaxine slow-release formulation capable of providing 24-h release result and preparation method of venlafaxine slow-release formulation |
Non-Patent Citations (1)
| Title |
|---|
| AKELESH T，ET AL.: "Formulation development and evaluation of Venlafaxine hydrochloride sustained release pellets", 《JOURNAL OF PHARMACY RESEARCH》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112402395A (en) * | 2020-10-28 | 2021-02-26 | 海南卫康制药(潜山)有限公司 | Venlafaxine sustained-release capsule composition and preparation process thereof |
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