CN108888604A - Delay CONTROLLED RELEASE OSMOTIC pump controlled-releasing tablet and preparation method thereof when a kind of Milnacipran is selected - Google Patents
Delay CONTROLLED RELEASE OSMOTIC pump controlled-releasing tablet and preparation method thereof when a kind of Milnacipran is selected Download PDFInfo
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- CN108888604A CN108888604A CN201810847100.6A CN201810847100A CN108888604A CN 108888604 A CN108888604 A CN 108888604A CN 201810847100 A CN201810847100 A CN 201810847100A CN 108888604 A CN108888604 A CN 108888604A
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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
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
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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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2086—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/2853—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers, poly(lactide-co-glycolide)
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
- A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- 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
Abstract
The present invention discloses delay CONTROLLED RELEASE OSMOTIC pump controlled-releasing tablet and preparation method thereof when a kind of Milnacipran is selected, and semi-permeable membrane of the controlled release tablet by label and with release hole forms, and the label is made of medicated layer and promoting layer, and the group of medicated layer becomes：Milnacipran and hot melt auxiliary material are prepared into hot-melt extruded object, preferably composition of the hot melt auxiliary material for PVP and PEG, weight ratio 4:1-10:1；The group of promoting layer becomes：Polyoxyethylene, osmotic pressure active material, povidone etc.；Medicated layer and promoting layer are pressed into packet semi-permeable membrane after double-layer tablets, punching.Technical solution of the present invention reaches effective controlled release of drug, and the drug effect blank phase occurs in reduction, and the osmotic pump controlled release tablet release in vitro prepared using hot-melt extruded method is more complete, more meets Zero order release feature, improves the bioavilability and stability of product.
Description
Technical field
Postpone CONTROLLED RELEASE OSMOTIC the present invention relates to pharmaceutical preparations technology field, in particular to when a kind of Milnacipran is selected and pumps controlled release
Piece and preparation method thereof.
Background technique
Milnacipran (milnacipran, trade name Ixel, chemistry entitled 1- phenyl -2- amine methyl cyclopropane-N, N-
Diethylformamide) it is a kind for the treatment of developed by French Pf Medicament and in listing in 1997
The drug of depression, Milnacipran belong to serotonin and norepinephrine reuptake inhibitors (SNRI), which is the 4th
For antidepressants, neuron can be inhibited simultaneously to the re-absorption of serotonin and norepinephrine, and action intensity is similar,
The product can be also used for the treatment of such as fatigue, pain, fibromyalgia and irritable bowel syndrome disease.But some meter Na Pu
The problems such as that there are stability is poor for preparation, the composition of logical sequence, and bioavilability is low.
Such as application No. is the applications for a patent for invention of CN1232387A to disclose the galenic of extended release meter Na Pulun a kind of
Preparation contains hydroxypropyl methyl cellulose in the particle of said preparation, outer to be distributed one layer of acrylic resin films, or uses propylene
Acid resin coating, wherein each ingredient of acrylic resin and meter Na Pulun particle respectively works respectively, and said preparation is not
The consistent effect of release behavior being able to achieve in gastric juice and intestinal juice.And occurring with the application of mass production while also some
Problem：Loss late is larger；Production efficiency is lower (yield is also with regard to 60-100kg within one day)；Mainly based on film control, stability is bad；
To the more demanding of worker operation, the training of long period is needed to practice to grasp.
Such as application No. is the applications for a patent for invention of CN102793683A to disclose a kind of sustained release containing left-handed Milnacipran
Composition, active constituent include left-handed Milnacipran or its pharmaceutically acceptable salt, which is characterized in that further comprise as parent
The high viscosity hydroxypropyl methylcellulose of aquogel type sustained-release matrix material and acrylic resin as pH adjusting agent；Its each component institute
Accounting for weight is：Left-handed Milnacipran or 10-70 parts of its pharmaceutically acceptable salt, 5-30 parts of hydroxypropyl methylcellulose, third
3.5-7.5 parts of olefin(e) acid resin；When preparation, have to mix left-handed Milnacipran, hydroxypropyl methylcellulose and acrylic resin equal
It is even.Though making moderate progress relative to already known processes scheme, also it is difficult to reach effective controlled release of drug, in fact it could happen that drug effect is empty
Bai Qi.
Summary of the invention
In view of the problems of the existing technology, the present invention, which provides, postpones CONTROLLED RELEASE OSMOTIC pump controlled-releasing tablet when a kind of Milnacipran is selected
And preparation method thereof.
To achieve the goals above, technical solution of the present invention is as follows：
Postpone CONTROLLED RELEASE OSMOTIC pump controlled-releasing tablet when a kind of Milnacipran is selected, is made of label and the semi-permeable membrane with release hole, institute
It states label to be made of medicated layer and promoting layer, wherein medicated layer and the weight ratio of promoting layer are [(110 ± 6)~(210 ± 15)]:
[(70 ± 5)~(86 ± 10)]；
The group of medicated layer becomes：Milnacipran and hot melt auxiliary material are prepared into hot-melt extruded object, heat auxiliary material and Milnacipran
Weight ratio be 20:1~3:1, hot melt auxiliary material is povidone (PVP) and/or polyethylene glycol (PEG)；
The group of promoting layer becomes：Molecular weight is 500-800 ten thousand and parts by weight are 10-200 parts polyoxyethylene, 5-250 parts
Osmotic pressure active material, 0.005-20 part povidone, 0-50 parts of modified celluloses, 0.005-20 parts of lubricants, 0-40 parts of oxidations
Iron oxide red；
Medicated layer and promoting layer are pressed into packet semi-permeable membrane after double-layer tablets, the vinegar that the semi-permeable membrane is 4-120 parts by parts by weight
The polyethylene glycol composition that acid cellulose and parts by weight are 2-80 parts and molecular weight is 2000-6000 ten thousand, semipermeable membrane weight is label
The 4-30% of weight uses 1-10 hole of machine drilling method or laser punching legal system, aperture control on the semi-permeable membrane of medicated layer side
It is made as 0.2mm-1mm.
Preferably, the osmotic pressure active material is selected from one of sodium chloride, potassium chloride, mannitol, sorbierite or more
Kind；The modified cellulose is selected from one of carboxymethyl cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose or a variety of.
Preferably, the hot melt auxiliary material is PVPS630：PEG2000=8:1, weight ratio 4:1~10:1.
Preferably, weight ratio is PVPS630 in the hot-melt extruded object：PEG2000：Milnacipran=8:1:1.
Postpone the preparation method of CONTROLLED RELEASE OSMOTIC pump controlled-releasing tablet when selecting the present invention also provides a kind of Milnacipran, including following
Step：
(1), Milnacipran and PVPS630, PEG2000 are crossed into 60 meshes respectively, after mixing, are placed in the loading hopper of extruder
In, revolving speed 20r/min is controlled, temperature is 120 DEG C, and material is squeezed out via head die hole with form of strips, and room temperature is cooling, with whole
Grain machine whole grain crosses 40 meshes, takes out, spare；
(2), each component in addition to lubricant of promoting layer is mixed respectively, is pelletized, lubricant is added after dry；
(3), medicated layer and propulsion are laminated into double-layer tablets；
(4), filmogen cellulose acetate is taken, acetone is added, solution is made, adding pore-foaming agent molecular weight is 2000-
Semi-permeable membrane coating solution is made in 6000 parts of polyethylene glycol, in double-layer tablets outsourcing semi-permeable membrane, until label weight gain 4%~30%, is containing
1~10 hole of machine drilling method or laser punching legal system is used on the semi-permeable membrane of medicine layer side, pore size control is 0.2mm~1mm.
Preferably, the dosage of pore-foaming agent and filmogen should be 1 in semi-permeable membrane in the step (4):9~3:7 range
It is interior.
Preferably, 1~4 hole is made in the step (4), pore size control is 0.4mm~0.5mm.
Using technical solution of the present invention, have the advantages that：Osmotic pump tablet, phase are provided by hot melt preparation method
For the osmotic pump tablet of non-hot-melt extruded, bioavilability can be improved using the osmotic pump tablet of hot-melt extruded；It wherein heats auxiliary
Expect PVPS630：PEG6000=8:When 1, the bioavilability highest of osmotic pump tablet.
The permeability and label that the dosage for reducing pore-foaming agent reduces semi-permeable membrane are extended using the polyoxyethylene of higher molecular weight
The hydration time of label, has the function that sustained release, seeps water to increase the surface area of tablet by lowering single dose
The area increase into label is penetrated into, in this way, ensure that can into the water in label in the case where reducing semi-transparent membrane permeability
To meet the needs of release.
Semi-permeable membrane of the invention is to control drug release time and rate of release since in osmotic pumps；Pore-foaming agent is logical
It crosses and forms small hole on semi-permeable membrane, to improve the permeability of semi-permeable membrane, in order to discharge drug within the time of selection,
And subsequent release is made to meet 0 grade of release rule.
Process due to reducing packet delay layer, reduces the dosage of organic solvent, reduces technology difficulty, improve work
The controllability of skill, at the same reduce organic solvent use and the harm to the pollution of environment and to operator's body, it is both simple
Change technical process, and greatly reduces production cost.
Detailed description of the invention
Fig. 1 is delay CONTROLLED RELEASE OSMOTIC pump controlled-releasing tablet schematic diagram when selecting of the invention.
Specific embodiment
Below in conjunction with the drawings and specific embodiments, the present invention is further described.
Embodiment 1
Shown in referring to Fig.1：
It is prepared by medicated layer 1：Milnacipran and PVPS630, PEG2000 are crossed into 60 meshes respectively, according to mass ratio=8：1：1
It after mixing, is placed in the loading hopper of extruder, revolving speed 20r/min, temperature is 120 DEG C, and material is via head die hole with strip
Object shape squeezes out, and room temperature is cooling, crosses 40 meshes with pelletizing machine whole grain, takes out, spare.
The preparation of promoting layer 2：Take polyoxyethylene (PEO, molecular weight：600 ten thousand) 75g, povidone k 300.5g, sodium chloride
8g, iron oxide red 2g are uniformly mixed, and add ethyl alcohol stirring granulation, in 45 DEG C of drying 2h, let cool to room temperature, take out, whole with 24 meshes
Magnesium stearate 0.42g is added in grain, mixes.
Tabletting：Using pressing the double-deck chip technology to suppress 100 double-layer tablets, resulting tablet medicated layer weight is 210mg ± 15mg
(Milnacipran 20mg specification)；Promoting layer weight is 86mg ± 10mg；Average plate core weight is 296mg ± 15mg.
The good double-layer tablets label packet semi-permeable membrane 3 of pressure：Cellulose acetate 45.0g is taken, acetone 1500ml is added, stirring makes molten
Solution.Another taking polyethylene glycol (molecular weight：4000) 10.0g is set in the measuring bottle of 100ml, after adding water 50ml to make it dissolve, adds water to quarter
Degree, shakes up, 90ml is taken to be added in above-mentioned 1500ml cellulose acetate acetone soln, stirring while adding, keeps polyethylene glycol whole
Coating solution is made in dissolution.Double-layer tablets obtained above are set in coating pan, leads to hot wind, maintains the temperature between 30-40 DEG C, are sprayed
Enter coating solution, until averagely every weight gain 46mg-55mg.
Drilling：The release hole for being 0.5mm with two apertures of laser or mechanical means system on the semi-permeable membrane of medicated layer side,
This preparation is made.
Embodiment 2
The preparation process of the present embodiment continues the preparation process of embodiment 1, the difference is that by Milnacipran with
PVPS630, PEG2000 cross 60 meshes respectively, according to mass ratio=8：2：1 mixes, other same as Example 1.
Embodiment 3
The preparation process of the present embodiment continues the preparation process of embodiment 1, the difference is that by Milnacipran with
PVPS630, PEG6000 cross 60 meshes respectively, according to mass ratio=8：1：1 mixes, other same as Example 1.
Embodiment 4
Medicated layer preparation：Milnacipran and PVPS630, PEG2000 are crossed into 60 meshes respectively, according to mass ratio=8：1：1
It after mixing, is placed in the loading hopper of extruder, revolving speed 20r/min, temperature is 120 DEG C, and material is via head die hole with strip
Object shape squeezes out, and room temperature is cooling, crosses 40 meshes with pelletizing machine whole grain, takes out, spare.
The preparation of promoting layer：Take polyoxyethylene (PEO, molecular weight：600 ten thousand) 75g, povidone k 300.5g, sodium chloride 8g,
Iron oxide red 2g is uniformly mixed, and ethyl alcohol stirring granulation is added to let cool in 45 DEG C of drying 2h to room temperature, taking-up, with 24 mesh sieves,
Magnesium stearate 0.42g is added, mixes.
Tabletting：Using pressing the double-deck chip technology to suppress 100 double-layer tablets, resulting tablet medicated layer weight is 210mg ± 15mg
(Milnacipran 20mg specification)；Promoting layer weight is 86mg ± 10mg；Average plate core weight is 296mg ± 15mg.
The double-layer tablets label packet semi-permeable membrane pressed：Cellulose acetate 30.0g is taken, adds acetone 1000ml, is stirred to dissolve.Separately
Taking polyethylene glycol (molecular weight：4000) 10.0g is set in the measuring bottle of 100ml, is added water 50ml to make to dissolve, is added water to scale, shakes up,
It takes 60ml to be added in above-mentioned 1000ml cellulose acetate acetone soln, stirs, make whole dissolutions, coating solution is made.Take bilayer
Piece is set in coating pan, is led to hot wind, is maintained the temperature between 30-40 DEG C, coating solution is sprayed into, until averagely every weight gain 26mg-
35mg。
Drilling：The release hole for being 0.5mm with two apertures of laser or mechanical means system on the semi-permeable membrane of medicated layer side,
This preparation is made.
Comparative example 1
Postpone CONTROLLED RELEASE OSMOTIC pump controlled-releasing tablet when Milnacipran is selected
Medicated layer preparation：PEO (molecular weight 1,000,000) 40g is taken, 60 meshes are crossed, sodium chloride 9g crosses 80 meshes, with meter Na Pu
Logical sequence 30g is uniformly mixed, and using 35ml ethyl alcohol as wetting agent, softwood processed crosses the granulation of 30 meshes, and magnesium stearate is added in 45 DEG C of drying 2h
1.05g is mixed, spare.
The preparation of promoting layer：Take polyoxyethylene (PEO, molecular weight：600 ten thousand) 75g, povidone k300.5g, sodium chloride 8g,
Iron oxide red 2g is uniformly mixed, and ethyl alcohol stirring granulation is added to let cool in 45 DEG C of drying 2h to room temperature, taking-up, with 24 mesh sieves,
Magnesium stearate 0.42g is added, mixes.
Tabletting：Using pressing the double-deck chip technology to suppress 100 double-layer tablets, resulting tablet medicated layer weight is 210mg ± 15mg
(Milnacipran 20mg specification)；Promoting layer weight is 86mg ± 10mg；Average plate core weight is 296mg ± 15mg.
The good double-layer tablets label packet semi-permeable membrane of pressure：Cellulose acetate 45.0g is taken, adds acetone 1500ml, is stirred to dissolve.
Another taking polyethylene glycol (molecular weight：4000) 10.0g is set in the measuring bottle of 100ml, after adding water 50ml to make it dissolve, adds water to scale,
It shakes up, 90ml is taken to be added in above-mentioned 1500ml cellulose acetate acetone soln, it is stirring while adding, keep polyethylene glycol all molten
Coating solution is made in solution.Double-layer tablets obtained above are set in coating pan, leads to hot wind, maintains the temperature between 30-40 DEG C, are sprayed into
Coating solution, until averagely every weight gain 46mg-55mg.
Drilling：The release hole for being 0.5mm with two apertures of laser or mechanical means system on the semi-permeable membrane of medicated layer side,
This preparation is made.
Comparative example 2
Postpone CONTROLLED RELEASE OSMOTIC pump controlled-releasing tablet when Milnacipran is selected
Medicated layer preparation：Milnacipran and PVPS630, PEG2000 are crossed into 60 meshes respectively, according to mass ratio=8：1：1
After mixing, 40 meshes are crossed with pelletizing machine whole grain, are taken out, it is spare.
The preparation of promoting layer：Take polyoxyethylene (PEO, molecular weight：600 ten thousand) 75g, povidone k300.5g, sodium chloride 8g,
Iron oxide red 2g is uniformly mixed, and ethyl alcohol stirring granulation is added to let cool in 45 DEG C of drying 2h to room temperature, taking-up, with 24 mesh sieves,
Magnesium stearate 0.42g is added, mixes.
Tabletting：Using pressing the double-deck chip technology to suppress 100 double-layer tablets, resulting tablet medicated layer weight is 210mg ± 15mg
(Milnacipran 20mg specification)；Promoting layer weight is 86mg ± 10mg；Average plate core weight is 296mg ± 15mg.
The good double-layer tablets label packet semi-permeable membrane of pressure：Cellulose acetate 45.0g is taken, adds acetone 1500ml, is stirred to dissolve.
Another taking polyethylene glycol (molecular weight：4000) 10.0g is set in the measuring bottle of 100ml, after adding water 50ml to make it dissolve, adds water to scale,
It shakes up, 90ml is taken to be added in above-mentioned 1500ml cellulose acetate acetone soln, it is stirring while adding, keep polyethylene glycol all molten
Coating solution is made in solution.Double-layer tablets obtained above are set in coating pan, leads to hot wind, maintains the temperature between 30-40 DEG C, are sprayed into
Coating solution, until averagely every weight gain 46mg-55mg.
Drilling：The release hole for being 0.5mm with two apertures of laser or mechanical means system on the semi-permeable membrane of medicated layer side,
This preparation is made.
Dissolution measurement
According to drug release determination method (two the first methods of annex XD of Chinese Pharmacopoeia version in 2010), using dissolution method first
The device of method, respectively with 0.1mol/L hydrochloric acid solution, phosphate buffer (pH6.8) for dissolution medium, revolving speed is per minute 100
Turn, operate according to methods, is sampled in 2h, 4h, 8h, 12h, according to UV-vis spectroscopy light method (Chinese Pharmacopoeia two annex of version in 2010
IVA it) measures absorbance respectively at the wavelength of 295nm, measures the every burst size in different time.As a result such as table 1, table 2：
Table 1
Table 2
From the above as it can be seen that co-action, makes left-handed Milnacipran in 0.1M using prescription and technique of the invention
Hydrochloric acid solution reaches consistent with phosphate buffer (pH6.8) release.And the release of each point of release is close, it is effective to realize
Timing and controlled release.Due to not using the releasing effect of hot melt material prescription and preparation.
Vivo efficacy measurement
In vivo assay Cells：With healthy male Beagle dog (10kg ± 0.5kg), the osmotic pump tablet of Milnacipran is taken orally
(20mg/ piece) 1；Before administration 0.25 after (0h), administration, 0.5,1,1.5,2,3,4,6,10,12, in dog forelimb take blood for 24 hours
2ml is placed in calparine pipe, centrifuging and taking supernatant, is set in refrigerator and is freezed for use, under the curve for calculating blood concentration-time in -35 DEG C
Area.
Table 3
Test result is shown in Table 3, it can be seen that technical solution of the present invention bioavilability is excellent.
Stability Determination
The illumination of 4500LX ± 500LX, 60 DEG C of ± 2 DEG C of high temperature, 92.5% ± 5% high humidity insulating box in place 10
It, total miscellaneous measurement result is as follows, and measuring method is the same as embodiment 5.
Table 4
Test result is shown in Table 4, it can be seen that technical solution of the present invention quality stability is excellent.
The above embodiment is a preferred embodiment of the present invention, but embodiments of the present invention are not by above-described embodiment
Limitation, other any changes, modifications, substitutions, combinations, simplifications made without departing from the spirit and principles of the present invention,
It should be equivalent substitute mode, be included within the scope of the present invention.
Claims (7)
1. postponing CONTROLLED RELEASE OSMOTIC pump controlled-releasing tablet when a kind of Milnacipran is selected, which is characterized in that by label and with the semi-transparent of release hole
Film composition, the label is made of medicated layer and promoting layer, wherein medicated layer and the weight ratio of promoting layer be [(110 ± 6)~
(210 ± 15)]: [(70 ± 5)~(86 ± 10)]；
The group of medicated layer becomes：Milnacipran and hot melt auxiliary material are prepared into hot-melt extruded object, heat the weight of auxiliary material and Milnacipran
Amount is than being 20:1~3:1, hot melt auxiliary material is povidone (PVP) and/or polyethylene glycol (PEG)；
The group of promoting layer becomes：Molecular weight is 500-800 ten thousand and parts by weight are 10-200 parts polyoxyethylene, 5-250 parts of infiltrations
Press active material, 0.005-20 parts of povidone, 0-50 parts of modified celluloses, 0.005-20 parts of lubricants, 0-40 parts of iron oxide reds；
Medicated layer and promoting layer are pressed into packet semi-permeable membrane after double-layer tablets, and the semi-permeable membrane is fine by the acetic acid that parts by weight are 4-120 parts
Dimension element and the polyethylene glycol composition that parts by weight are 2-80 parts and molecular weight is 2000-6000 ten thousand, semipermeable membrane weight are label weight
4-30%, 1-10 hole of machine drilling method or laser punching legal system is used on the semi-permeable membrane of medicated layer side, pore size control is
0.2mm-1mm。
2. postponing CONTROLLED RELEASE OSMOTIC pump controlled-releasing tablet when Milnacipran according to claim 1 is selected, which is characterized in that wherein described
Osmotic pressure active material is selected from one of sodium chloride, potassium chloride, mannitol, sorbierite or a variety of；The modified cellulose
Selected from one of carboxymethyl cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose or a variety of.
3. postponing CONTROLLED RELEASE OSMOTIC pump controlled-releasing tablet when Milnacipran according to claim 1 is selected, which is characterized in that wherein heat
Auxiliary material is PVPS630：PEG2000=8:1, weight ratio 4:1~10:1.
4. postponing CONTROLLED RELEASE OSMOTIC pump controlled-releasing tablet when Milnacipran according to claim 3 is selected, which is characterized in that hot-melt extruded
Weight ratio is PVPS630 in object：PEG2000：Milnacipran=8:1:1.
5. a kind of prepare the preparation side for postponing CONTROLLED RELEASE OSMOTIC pump controlled-releasing tablet when the described in any item Milnaciprans of claim 1-4 are selected
Method, which is characterized in that include the following steps：
(1), Milnacipran and PVPS630, PEG2000 are crossed into 60 meshes respectively, after mixing, are placed in the loading hopper of extruder,
Revolving speed 20r/min is controlled, temperature is 120 DEG C, and material is squeezed out via head die hole with form of strips, and room temperature is cooling, with whole grain
Machine whole grain crosses 40 meshes, takes out, spare；
(2), each component in addition to lubricant of promoting layer is mixed respectively, is pelletized, lubricant is added after dry；
(3), medicated layer and propulsion are laminated into double-layer tablets；
(4), filmogen cellulose acetate is taken, acetone is added, solution is made, adding pore-foaming agent molecular weight is 2000-6000
Part polyethylene glycol, semi-permeable membrane coating solution is made, in double-layer tablets outsourcing semi-permeable membrane, until label weight gain 4%~30%, in medicated layer
1~10 hole of machine drilling method or laser punching legal system is used on the semi-permeable membrane of side, pore size control is 0.2mm~1mm.
6. postponing the preparation method of CONTROLLED RELEASE OSMOTIC pump controlled-releasing tablet when Milnacipran according to claim 5 is selected, feature exists
In the dosage of pore-foaming agent and filmogen should be 1 in semi-permeable membrane in the step (4):9~3:In the range of 7.
7. postponing the preparation method of CONTROLLED RELEASE OSMOTIC pump controlled-releasing tablet when Milnacipran according to claim 5 is selected, feature exists
In 1~4 hole of system in the step (4), pore size control is 0.4mm~0.5mm.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810847100.6A CN108888604A (en) | 2018-07-27 | 2018-07-27 | Delay CONTROLLED RELEASE OSMOTIC pump controlled-releasing tablet and preparation method thereof when a kind of Milnacipran is selected |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810847100.6A CN108888604A (en) | 2018-07-27 | 2018-07-27 | Delay CONTROLLED RELEASE OSMOTIC pump controlled-releasing tablet and preparation method thereof when a kind of Milnacipran is selected |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN108888604A true CN108888604A (en) | 2018-11-27 |
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|---|---|---|---|
| CN201810847100.6A Pending CN108888604A (en) | 2018-07-27 | 2018-07-27 | Delay CONTROLLED RELEASE OSMOTIC pump controlled-releasing tablet and preparation method thereof when a kind of Milnacipran is selected |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
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| CN101152158A (en) * | 2007-08-21 | 2008-04-02 | 浙江大学 | Method of producing double-layer core permeation pump patch of medicament |
| CN104127401A (en) * | 2013-08-28 | 2014-11-05 | 山东绿叶制药有限公司 | Osmotic pump control-released composition containing desmethylvenlafaxine benzoate compound |
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