CN100463676C - Control releasing venlafaxine hydrochloride tablet and its prepn - Google Patents
Control releasing venlafaxine hydrochloride tablet and its prepn Download PDFInfo
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- CN100463676C CN100463676C CNB2004100906563A CN200410090656A CN100463676C CN 100463676 C CN100463676 C CN 100463676C CN B2004100906563 A CNB2004100906563 A CN B2004100906563A CN 200410090656 A CN200410090656 A CN 200410090656A CN 100463676 C CN100463676 C CN 100463676C
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Abstract
The present invention discloses one kind of control releasing venlafaxine hydrochloride tablet and its preparation process. The control releasing venlafaxine hydrochloride tablet consists of medicine core of venlafaxine hydrochloride and semi-permeable coating with pores. The medicine core consists of venlafaxine hydrochloride 75 weight portions, stuffing 30-250 weight portions, osmotic pressure promoter 1-50 weight portions, adhesive 1-20 weight portions and lubricant 0.1-20 weight portions. The preparation has reasonable composition, excellent control releasing effect, long effective time, less side effect on gastrointestinal tract, less differential personal effect, high safety and good compliance.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, exactly relate to a kind of controlled-release tablet preparation of novel antidepressant VENLAFAXINE HCL, and relate to the preparation method of this controlled-release tablet preparation.
Background technology
Venlafaxine is a kind of novel antidepressant, has instant effect (4 days-1 weeks), better tolerance, short-term and all good distinguishing feature of long-term treatment effect.At present, gone on the market both at home and abroad or the Effexor of existing report has the ordinary preparation and the slow releasing preparation of different size, as conventional capsule agent, slow releasing tablet, slow releasing capsule and slow-release pill etc.But the venlafaxine of ordinary preparation exists half-life short (about 5 ± 2 hours), patient to need problems such as frequent drug administration (every day 2-3 times) and side effect are bigger.Need the problem of frequent drug administration (only need take medicine once every day) though slow releasing preparation has solved above-mentioned ordinary preparation, also can reduce gastrointestinal side effect to a certain extent; But, because slow releasing preparation is non-lentamente constant release, the release of medicine and infiltration rate also are subjected to the influence of factor such as gastric juice or intestinal juice in the patient body, be difficult to control and expectation, so its blood drug level still has bigger fluctuation, has certain unstability, the size of its effective persistent period and gastrointestinal side effect also varies with each individual, the influence of individual variation is bigger, has uncontrollability.Patient is also often because need frequently take medicine or side effect is big and compliance is poor.
1974, Theeuwes proposed the notion and the structure of elementary elementary osmotic pump, made osmotic pump preparation move towards suitability for industrialized production and clinical practice application.The principle of osmotic pump preparation be utilize the permeability of medicine self and some osmotic pressure promoter be used for provide power for release, in use, in moisture sucks sheet from semipermeable membrane, make to form very high osmotic pressure in the sheet, thereby the saturated aqueous solution that makes medicine in the sheet is disengaged by the aperture on sheet surface; Because semipermeable membrane does not have ductility, the volume in the film remains constant, thus if solid drugs not dissolving fully as yet in the sheet, its saturated solution will be released continuously, thereby reach the effect of constant speed release medicine.But, if different concrete medicines is made the preferable osmotic pump preparation of controlled-release effect, still have many problems that need solution and overcome, comprise that as adjuvant the kind of osmotic pressure promoter, filler, binding agent, lubricant etc. is selected and consumption is selected, and the proportioning between concrete medicine and the various adjuvant or the like.
Summary of the invention
Purpose of the present invention just provides a kind of VENLAFAXINE HCL controlled-release tablet preparation, said preparation is formed rationally, can be reached controlled-release effect preferably, and effectively longer duration, every day only need take medicine once, gastrointestinal side effect is littler, the influence of individual variation is less, safety good, patient dependence is good.
Another object of the present invention provides a kind of preparation method of VENLAFAXINE HCL controlled-release tablet preparation.
The technical solution adopted for the present invention to solve the technical problems is: a kind of VENLAFAXINE HCL controlled-release tablet preparation is provided, be made of medicine label that comprises VENLAFAXINE HCL and the semi permeability film coating that has aperture, its Chinese medicine label is made up of 75 parts of VENLAFAXINE HCL, 30-250 part filler, 1-50 part osmotic pressure promoter, 1-20 part binding agent and 0.1-20 part lubricant; The semi permeability film coating is made up of 5-15 part semipermeable membrane coating material and 1 part of plasticizer, more than and part be weight portion hereinafter described, weight can represent with any unit of weight, as milligram, gram, kilogram, ton.
Wherein, osmotic pressure promoter is meant any one or more than one the mixture of potassium chloride, sodium chloride, magnesium chloride, potassium sulfate, sodium sulfate, magnesium sulfate etc., in preferred potassium chloride, sodium chloride, the magnesium chloride any one or more than one; Filler is meant any one or more than one the mixture of microcrystalline Cellulose, dextrin, starch and derivant thereof, mannitol, sorbitol, lactose, sucrose etc., preferably microcrystalline cellulose; Binding agent is meant any one or more than one the mixture of the mixed solution of polyvidone, methylcellulose, sodium carboxymethyl cellulose, carboxylic propyl methocel, water, water or alcohol etc.; Lubricant is meant magnesium stearate etc.
The semipermeable membrane coating material is meant any one or more than one the mixture of cellulose acetate, ethyl cellulose, cellulose propionate, Merlon, polyethylene, polyvinyl alcohol, vinylacetate etc.; Plasticizer is meant any one or more than one the mixture of phthalate, glyceride, succinate, benzoate, phosphate ester, adipate ester, tartrate, polyethylene glycols etc., any one or more than one the mixture of preferred diethyl phthalate, polyethylene glycol 1500 or Macrogol 4000 etc.
The medicine label can be made up of following components in weight percentage: 75 parts of VENLAFAXINE HCL, 30-250 part microcrystalline Cellulose, 1-50 part sodium chloride, 1-20 part 30 POVIDONE K 30 BP/USP 30,0.1-20 part magnesium stearate.
The composition optimum ratio of medicine label is: 75 parts of VENLAFAXINE HCL, 100-120 part microcrystalline Cellulose, 1-30 part sodium chloride, 1-15 part 30 POVIDONE K 30 BP/USP 30,0.1-10 part magnesium stearate.More preferably proportioning is: 75 parts of VENLAFAXINE HCL, 112-116 part microcrystalline Cellulose, 3-5 part sodium chloride, 5-7 part 30 POVIDONE K 30 BP/USP 30,0.5-2 part magnesium stearate.
The best proportioning of the composition of medicine label is: 75 parts of VENLAFAXINE HCL, 114 parts of microcrystalline Cellulose, 4 parts of sodium chloride, 30,1 part of magnesium stearate of 6 parts of 30 POVIDONE K 30 BP/USPs.
The semi permeability film coating can be made up of following components in weight percentage: 5-15 part cellulose acetate, 0.6-0.9 part diethyl phthalate and 0.1-0.4 part polyethylene glycol 1500; Optimum ratio is: 6-12 part cellulose acetate, 0.6-0.9 part diethyl phthalate and 0.1-0.4 part polyethylene glycol 1500; More preferably proportioning is: 8-10 part cellulose acetate, 0.75-0.80 part diethyl phthalate and 0.20-0.25 part polyethylene glycol 1500; Best proportioning is: 9 parts of cellulose acetate, 0.78 part of diethyl phthalate and 0.22 part of polyethylene glycol 1500.
Wherein, the film-coated weight proportion of medicine label and semi permeability is 1:0.02-0.05; Optimum ratio is 1:0.03-0.04.
On the semi permeability film coating of above-mentioned VENLAFAXINE HCL controlled release preparation, can one or more small delivery aperture, preferred one of little hole number be arranged with laser or additive method preparation; Its diameter is 0.2-1.0mm, preferred 0.4-0.8mm.
Above-mentioned VENLAFAXINE HCL controlled-release tablet preparation can prepare by the method that may further comprise the steps:
(1) preparation medicine label: get VENLAFAXINE HCL, filler, osmotic pressure promoter and the binding agent of described proportioning, mix homogeneously is granulated according to a conventional method, the lubricant that adds described proportioning again, mixing, tabletting promptly makes the medicine label that contains VENLAFAXINE HCL;
(2) preparation coating solution: get the semipermeable membrane coating material and the plasticizer of described proportioning, mix homogeneously adds an amount of coating solvent, mixing, and it is standby to make coating solution;
(3) coating: the coating solution that the medicine label that makes of (1) step and (2) step are made places coating pan, and coating makes coated tablet according to a conventional method, and coated tablet is dry under 30-60 ℃ of condition, obtains exsiccant coated tablet;
(4) punch: go on foot on the exsiccant coated tablet that makes in (3) with laser or additive method and beat the aperture that one or more diameters are 0.2-1.0mm, promptly make the VENLAFAXINE HCL controlled-release tablet preparation.
Wherein, the coating solvent described in (2) step can be that volume ratio is acetone-water solution or the acetone-alcoholic solution of 4-20:1, also can be other coating solvents commonly used such as a certain proportion of methylene chloride-methanol solution; (3) the little hole number described in the step is preferred one, the preferred 0.4-0.8mm of its diameter.
Filler mannitol in the medicine label of being mentioned among the present invention, sorbitol, lactose, sucrose etc. mainly are as filler, but also have the effect of osmotic pressure promoter simultaneously concurrently; Polyethylene glycol 1500 mainly is as plasticizer in the semi permeability film coating, but also has the effect of porogen simultaneously concurrently, and it can improve the permeability of coating membrane, promotes the release of drug solution.
Produce above each embodiment VENLAFAXINE HCL controlled-release tablet preparation in a small amount as a trial, products obtained therefrom all meets the provisions of the relevant regulations issued by the State through researchs such as release investigation, assay, related substance inspection and solvent residual amount tests.
In order to reach ideal controlled-release effect, realize goal of the invention, the inventor is to influencing the kind and the consumption of bigger filler, the plasticizer in the coating membrane etc. to the pharmaceutical preparation release in the adjuvant, proportioning between VENLAFAXINE HCL and the various adjuvant, and the ratio of medicine label and coating membrane etc. carried out detailed investigation, obtained comparatively ideal results.
1, the selection of osmotic pressure promoter kind and consumption
It is reported that osmotic pressure promoter commonly used has inorganic salts such as sodium chloride, potassium chloride, magnesium chloride, potassium sulfate, sodium sulfate, magnesium sulfate etc., low molecule saccharide such as glucose, mannitol, sorbitol, lactose, sucrose, fructose etc.But through investigating, low molecule saccharide consumption as osmotic pressure promoter the time is very big, is not suitable among the present invention; Though Sulfates can be selected for use, its permeability is also poor, so preferably select hydrochlorates such as sodium chloride, potassium chloride or magnesium chloride in the present invention for use, can reach comparatively ideal controlled-release effect.
Show by the The effects result to the different amounts hydrochlorate: select the sodium chloride of 1-4%, the burst size of gained preparation and release wire sexual relationship are all better.
2, the selection of filler
In various adjuvants, the consumption of filler is relatively large, and its kind and consumption are bigger to the release influence of made tablet, so its selection is extremely important.
By to the investigating of filleies such as starch, dextrin, microcrystalline Cellulose, mannitol, sorbitol, lactose, sucrose, experimental result shows: comparatively desirable with the less microcrystalline Cellulose of disintegration etc., consumption is best with 40-70%.If the disintegration of filler is excessive, medicine is disintegrate rapidly in vivo, does not then reach the purpose of controlled release.
3, the selection of plasticizer in the coating membrane
Plasticizer is all influential to the coating outward appearance of preparation finished product and release etc., selects suitable plasticizer, can reach ideal outward appearance, dissolubility, permeability and release.The result shows by experiment: the selection molecular weight is 1500 or 4000 Polyethylene Glycol, when its consumption is 18-25%, medicament appearance is evenly smooth, discharge better, especially ideal with polyethylene glycol 1500, it has the effect of porogen simultaneously concurrently, makes coating membrane can form spongiform membrane structure after suction, improve the permeability of film, promote the release of drug solution.
4, the proportioning between VENLAFAXINE HCL and the various adjuvant
The inventor is by Orthogonal Experiment and Design and research, and repeated screening has been determined as optimum ratio between described VENLAFAXINE HCL of technical scheme part and the various adjuvant and best proportioning, and is safe and effective to guarantee final products, can reach the controlled release requirement simultaneously.
5, the selection of medicine label and coating membrane ratio
By investigation to the pharmaceutical preparation release of different clothing film weight, the result shows: when the weightening finish of control clothing film is 3-4%, the drug release curve is comparatively desirable, and can both guarantee the steady quality of product, so determine that the preferable range of preparation technology underpants film weightening finish is 3-4%.
For the release conditions of medicine of the present invention is described, the inventor has also carried out the release inspection, and its method is as follows:
Get three batches in the embodiment of the invention one prepared example pharmaceuticals preparation, according to 2000 editions two appendix XD drug release determinations of Chinese Pharmacopoeia method, first method, adopt the device of dissolution method, with distilled water 500ml is solvent, rotating speed is that per minute 50 changes, operation in accordance with the law, got solution 6ml respectively at the 2nd hour, 4 hours, 6 hours, 8 hours and 12 hours, 0.8 μ m filtering with microporous membrane, and in process container, replenish distilled water 6ml immediately, get subsequent filtrate,, measure trap respectively at the wavelength place of 274nm according to 2000 editions two appendix IVA spectrophotographys of Chinese Pharmacopoeia; It is an amount of that precision takes by weighing the VENLAFAXINE HCL reference substance in addition, makes the solution that contains 100 μ g among every 1ml approximately with distilled water, measures with method.Calculate every burst size respectively at different time.The results are shown in Table 1, three batch sample release profiles and see Figure of description 1:
Table 1 three batch sample release check results
Conclusion: medicine of the present invention is all up to specification in the burst size limit of 2 hours, 4 hours, 6 hours, 8 hours and 12 hours.Medicine of the present invention is 5 ~ 12% of labelled amount 2-8 hour average rate of release, and is up to specification.Its release meets the zero level dispose procedure substantially, and blood drug level can be maintained in the valid density scope for a long time more consistently, effectively longer duration.
In order to separate the medicine rule and the characteristics of dynamic change in animal body, provide reference to clinical rational drug use, the inventor has also carried out clinical preceding animal pharmacokinetics research to medicine VENLAFAXINE HCL controlled release tablet of the present invention, and method and result are as follows:
This test is a subjects with the beagle dog, is the time dependent rule of blood drug level of the reference preparation medicine of the present invention (75mg) of having studied same dose and calculates its pharmacokinetic parameter with venlafaxine hydrochloride sustained-release capsule (75mg).
Before the experiment, select 6 body weight, be divided into two groups at random the beagle of 6 ~ 8kg scope dog, settle one to be detained pin at its forelimb snapshot of oneself vein place, will make VENLAFAXINE HCL controlled release tablet and commercially available slow releasing capsule (75mg) by oneself by experienced poultry raiser then and insert the oral cavity epiglottis portion of beagle dog respectively, the beagle dog is swallowed automatically and inject the 20ml clear water and send down with intact tablet (capsule), after the administration 0,1,2,4,6,8,10,12,14,16,20,24, totally 13 time points of 30h gets forelimb venous blood 4ml, and immigration scribbles in the test tube of heparin centrifugal 10 minutes of 4000rpm immediately, separated plasma is put-20 ℃ of refrigerators then and is preserved stand-by.Intersect after the week at interval and take medicine, take a blood sample with quadrat method.The plasma drug level measurement result sees Table 3 and table 3, and average plasma concentration curve is seen Figure of description 2.
Table 2 VENLAFAXINE HCL controlled release tablet plasma drug level (ng.ml-1)
Table 3 venlafaxine hydrochloride sustained-release capsule plasma drug level (ng.ml
1)
The result shows: its Ke of VENLAFAXINE HCL controlled release tablet single dose administration is 0.16 ± 0.01h-1, and t1/2 is 4.50 ± 0.40h, and AUC is 1234.72 ± 222.65 (ng/ml) h, and Cmax is 92.51 ± 16.36ng/ml, and Tmax is 12.67 ± 1.03h; Its Ke of venlafaxine hydrochloride sustained-release capsule single dose administration is 0.17 ± 0.02h-1, and t1/2 is 4.15 ± 0.66h, and AUC is 1211.00 ± 185.88 (ng/ml) h, and Cmax is 83.66 ± 13.27ng/ml, and Tmax is 12.33 ± 1.51h.Compare with the venlafaxine hydrochloride sustained-release capsule, the pharmacokinetic parameter of VENLAFAXINE HCL controlled release tablet is not seen notable difference under same dose, peak time, elimination half-life, peak concentration and area under curve unknown significance difference, its relative bioavailability is 102.5%, bioequivalence.Release in vitro curve in conjunction with the VENLAFAXINE HCL controlled release tablet shows that the VENLAFAXINE HCL controlled release tablet has certain controlled-release effect, reach the peak after blood drug level comparatively steady, can better guarantee the lasting effectiveness and the safety of medicine of the present invention.
Compared with prior art, the invention has the beneficial effects as follows: adopt advanced controlled-release technology, VENLAFAXINE HCL is made the elementary osmotic pump tablet, be wrapped in the semipermeable membrane film coating of medicine sheet wicking surface, particularity because of its material character, only small-molecule substances such as water had permeability, even in gastrointestinal tract, also have only moisture to enter the medicine label by semipermeable membrane, make medicine be dissolved into saturated solution, osmotic pressure promoter then makes the interior solution of film become hyperosmotic solution, thereby impels medicine to pump from small delivery aperture, its drug release rate is not subjected to the influence of gastrointestinal tract pH value, thereby the influence of individual variation is less.And medicine release in vivo meets the zero level dispose procedure substantially, and promptly with constant speed or near constant release, blood drug level can maintain in the valid density scope for a long time more consistently.Effectively longer duration can reduce administration number of times, and only need take medicine once every day, and drug effect can reach 24 hours, taking convenience; Blood drug level is steady, and it is less to fluctuate, and can avoid occurring peak valley phenomenon, and gastrointestinal side effect is littler, and safety is good.Because of taking convenience, side effect are little, can guarantee curative effect of medication again, also can improve patient's compliance, particularly has good especially effect through preferred prescription.
Description of drawings
Fig. 1 is medicine three batch sample releasing curve diagrams of the present invention, and three batch sample release profiles almost completely overlap.
Fig. 2 is VENLAFAXINE HCL controlled release tablet (medicine embodiment one gained sample of the present invention) and the average plasma concentration curve figure of venlafaxine hydrochloride sustained-release capsule.
The specific embodiment
The present invention is described in further detail below in conjunction with the specific embodiment.
Embodiment one
The film-coated weight proportion of medicine label and semi permeability is the VENLAFAXINE HCL controlled-release tablet preparation of 1:0.035, wherein:
Consisting of of medicine label: 75 parts of VENLAFAXINE HCL, 114 parts of microcrystalline Cellulose, 4 parts of sodium chloride, 6 parts of 30 POVIDONE K 30 BP/USPs 30 and 1 part of magnesium stearate.
Semi permeability is film-coated to consist of: 9 parts of cellulose acetate, 0.78 part of diethyl phthalate and 0.22 part of polyethylene glycol 1500.
The preparation method of above-mentioned VENLAFAXINE HCL controlled-release tablet preparation may further comprise the steps:
(1) preparation medicine label: VENLAFAXINE HCL, microcrystalline Cellulose, sodium chloride and the 30 POVIDONE K 30 BP/USP 30 of getting described proportioning, mix homogeneously, add 95% alcoholic solution and make soft material in right amount, cross 20 mesh sieves and granulate, dry under 50 ℃ of conditions, with 18 mesh sieve granulate, the magnesium stearate that adds described proportioning again, mixing, tabletting promptly makes the medicine label that contains VENLAFAXINE HCL;
(2) preparation coating solution: get cellulose acetate, diethyl phthalate and the polyethylene glycol 1500 of described proportioning, mix homogeneously, the acetone-water solution that adds volume ratio and be 19:1 be in right amount as the coating solvent, mixing, and it is standby to make coating solution;
(3) coating: the coating solution that the medicine label that makes of (1) step and (2) step are made places coating pan, coating to coating weightening finish part is about 3.5% of medicine label according to a conventional method, promptly make coated tablet,, obtain exsiccant coated tablet coated tablet under 40 ℃ of conditions dry 24 hours;
(4) punching: the aperture that to make a call to a diameter on the exsiccant coated tablet that makes in (3) step with laser or additive method be 0.6mm, promptly making the film-coated weight proportion of medicine label and semi permeability is 1:0.035, the medicine label is made up of 75 parts of VENLAFAXINE HCL, 114 parts of microcrystalline Cellulose, 4 parts of sodium chloride, 6 parts of 30 POVIDONE K 30 BP/USPs 30 and 1 part of magnesium stearate, and the semi permeability film coating is by 9 parts of cellulose acetate, 0.78 part of diethyl phthalate and 0.22 part of VENLAFAXINE HCL controlled-release tablet preparation that polyethylene glycol 1500 is formed.
Embodiment two
The film-coated weight proportion of medicine label and semi permeability is the VENLAFAXINE HCL controlled-release tablet preparation of 1:0.05, wherein:
Consisting of of medicine label: 75 parts of VENLAFAXINE HCL, 120 parts of microcrystalline Cellulose, 1 part of sodium chloride, 15 parts of 30 POVIDONE K 30 BP/USPs 30 and 0.1 part of magnesium stearate.
Semi permeability is film-coated to consist of: 6 parts of cellulose acetate, 0.9 part of diethyl phthalate and 0.1 part of polyethylene glycol 1500.
The preparation method of above-mentioned VENLAFAXINE HCL controlled-release tablet preparation may further comprise the steps:
(1) preparation medicine label: VENLAFAXINE HCL, microcrystalline Cellulose, sodium chloride and the 30 POVIDONE K 30 BP/USP 30 of getting described proportioning, mix homogeneously, add 90% alcoholic solution and make soft material in right amount, cross 20 mesh sieves and granulate, dry under 40 ℃ of conditions, with 18 mesh sieve granulate, the magnesium stearate that adds described proportioning again, mixing, tabletting promptly makes the medicine label that contains VENLAFAXINE HCL;
(2) preparation coating solution: get cellulose acetate, diethyl phthalate and the polyethylene glycol 1500 of described proportioning, mix homogeneously, the acetone-alcoholic solution that adds volume ratio and be 20:1 be in right amount as the coating solvent, mixing, and it is standby to make coating solution;
(3) coating: the coating solution that the medicine label that makes of (1) step and (2) step are made places coating pan, coating to coating weightening finish part is about 5% of medicine label according to a conventional method, promptly make coated tablet,, obtain exsiccant coated tablet coated tablet under 60 ℃ of conditions dry 12 hours;
(4) punching: the aperture that to make a call to a diameter on the exsiccant coated tablet that makes in (3) step with laser or additive method be 0.8mm, promptly making the film-coated weight proportion of medicine label and semi permeability is 1:0.05, the medicine label is made up of 75 parts of VENLAFAXINE HCL, 120 parts of microcrystalline Cellulose, 1 part of sodium chloride, 15 parts of 30 POVIDONE K 30 BP/USPs 30 and 0.1 part of magnesium stearate, and the semi permeability film coating is by 6 parts of cellulose acetate, 0.9 part of diethyl phthalate and 0.1 part of VENLAFAXINE HCL controlled-release tablet preparation that polyethylene glycol 1500 is formed.
Embodiment three
The film-coated weight proportion of medicine label and semi permeability is the VENLAFAXINE HCL controlled-release tablet preparation of 1:0.02, wherein:
Consisting of of medicine label: 75 parts of VENLAFAXINE HCL, 100 parts of microcrystalline Cellulose, 30 parts of sodium chloride, 1 part of 30 POVIDONE K 30 BP/ USP 30 and 10 parts of magnesium stearate.
Semi permeability is film-coated to consist of: 12 parts of cellulose acetate, 0.6 part of diethyl phthalate and 0.4 part of polyethylene glycol 1500.
The preparation method of above-mentioned VENLAFAXINE HCL controlled-release tablet preparation may further comprise the steps:
(1) preparation medicine label: VENLAFAXINE HCL, microcrystalline Cellulose, sodium chloride and the 30 POVIDONE K 30 BP/USP 30 of getting described proportioning, mix homogeneously, add 95% alcoholic solution and make soft material in right amount, cross 20 mesh sieves and granulate, dry under 60 ℃ of conditions, with 18 mesh sieve granulate, the magnesium stearate that adds described proportioning again, mixing, tabletting promptly makes the medicine label that contains VENLAFAXINE HCL;
(2) preparation coating solution: get cellulose acetate, diethyl phthalate and the polyethylene glycol 1500 of described proportioning, mix homogeneously, the acetone-water solution that adds an amount of volume ratio and be 4:1 be in right amount as the coating solvent, mixing, and it is standby to make coating solution;
(3) coating: the coating solution that the medicine label that makes of (1) step and (2) step are made places coating pan, coating to coating weightening finish part is about 2% of medicine label according to a conventional method, promptly make coated tablet,, obtain exsiccant coated tablet coated tablet under 50 ℃ of conditions dry 18 hours;
(4) punching: the aperture that to make a call to a diameter on the exsiccant coated tablet that makes in (3) step with laser or additive method be 1.0mm, promptly making the film-coated weight proportion of medicine label and semi permeability is 1:0.02, the medicine label is made up of 75 parts of VENLAFAXINE HCL, 100 parts of microcrystalline Cellulose, 30 parts of sodium chloride, 1 part of 30 POVIDONE K 30 BP/ USP 30 and 10 parts of magnesium stearate, and the semi permeability film coating is by 12 parts of cellulose acetate, 0.6 part of diethyl phthalate and 0.4 part of VENLAFAXINE HCL controlled-release tablet preparation that polyethylene glycol 1500 is formed.
Embodiment four
The film-coated weight proportion of medicine label and semi permeability is the VENLAFAXINE HCL controlled-release tablet preparation of 1:0.045, wherein:
Consisting of of medicine label: 75 parts of VENLAFAXINE HCL, 250 parts of microcrystalline Cellulose, 1 part of sodium chloride, 1 part of 30 POVIDONE K 30 BP/ USP 30 and 20 parts of magnesium stearate.
Semi permeability is film-coated to consist of: 15 parts of cellulose acetate, 0.9 part of diethyl phthalate and 0.1 part of polyethylene glycol 1500.
The preparation method of above-mentioned VENLAFAXINE HCL controlled-release tablet preparation may further comprise the steps:
(1) preparation medicine label: VENLAFAXINE HCL, microcrystalline Cellulose, sodium chloride and the 30 POVIDONE K 30 BP/USP 30 of getting described proportioning, mix homogeneously, add 95% alcoholic solution and make soft material in right amount, cross 20 mesh sieves and granulate, dry under 50 ℃ of conditions, with 18 mesh sieve granulate, the magnesium stearate that adds described proportioning again, mixing, tabletting promptly makes the medicine label that contains VENLAFAXINE HCL;
(2) preparation coating solution: get cellulose acetate, diethyl phthalate and the polyethylene glycol 1500 of described proportioning, mix homogeneously, the acetone-water solution that adds an amount of volume ratio and be 19:1 be in right amount as the coating solvent, mixing, and it is standby to make coating solution;
(3) coating: the coating solution that the medicine label that makes of (1) step and (2) step are made places coating pan, coating to coating weightening finish part is about 4.5% of medicine label according to a conventional method, promptly make coated tablet,, obtain exsiccant coated tablet coated tablet under 40 ℃ of conditions dry 36 hours;
(4) punching: the aperture that to make a call to a diameter on the exsiccant coated tablet that makes in (3) step with laser or additive method be 0.9mm, promptly making the film-coated weight proportion of medicine label and semi permeability is 1:0.045, the medicine label is made up of 75 parts of VENLAFAXINE HCL, 250 parts of microcrystalline Cellulose, 1 part of sodium chloride, 1 part of 30 POVIDONE K 30 BP/ USP 30 and 20 parts of magnesium stearate, and the semi permeability film coating is by 15 parts of cellulose acetate, 0.9 part of diethyl phthalate and 0.1 part of VENLAFAXINE HCL controlled-release tablet preparation that polyethylene glycol 1500 is formed.
Embodiment five
The film-coated weight proportion of medicine label and semi permeability is the VENLAFAXINE HCL controlled-release tablet preparation of 1:0.04, wherein:
Consisting of of medicine label: 75 parts of VENLAFAXINE HCL, 30 parts of microcrystalline Cellulose, 50 parts of sodium chloride, 20 parts of 30 POVIDONE K 30 BP/USPs 30 and 0.1 part of magnesium stearate.
Semi permeability is film-coated to consist of: 5 parts of cellulose acetate, 0.6 part of diethyl phthalate and 0.4 part of polyethylene glycol 1500.
The preparation method of above-mentioned VENLAFAXINE HCL controlled-release tablet preparation may further comprise the steps:
(1) preparation medicine label: VENLAFAXINE HCL, microcrystalline Cellulose, sodium chloride and the 30 POVIDONE K 30 BP/USP 30 of getting described proportioning, mix homogeneously, add 95% alcoholic solution and make soft material in right amount, cross 20 mesh sieves and granulate, dry under 55 ℃ of conditions, with 18 mesh sieve granulate, the magnesium stearate that adds described proportioning again, mixing, tabletting promptly makes the medicine label that contains VENLAFAXINE HCL;
(2) preparation coating solution: get cellulose acetate, diethyl phthalate and the polyethylene glycol 1500 of described proportioning, mix homogeneously, the acetone-alcoholic solution that adds an amount of volume ratio and be 10:1 be in right amount as the coating solvent, mixing, and it is standby to make coating solution;
(3) coating: the coating solution that the medicine label that makes of (1) step and (2) step are made places coating pan, coating to coating weightening finish part is about 4% of medicine label according to a conventional method, promptly make coated tablet,, obtain exsiccant coated tablet coated tablet under 30 ℃ of conditions dry 36 hours;
(4) punching: the aperture that to make a call to a diameter on the exsiccant coated tablet that makes in (3) step with laser or additive method be 0.4mm, promptly making the film-coated weight proportion of medicine label and semi permeability is 1:0.04, the medicine label is made up of 75 parts of VENLAFAXINE HCL, 30 parts of microcrystalline Cellulose, 50 parts of sodium chloride, 20 parts of 30 POVIDONE K 30 BP/USPs 30 and 0.1 part of magnesium stearate, and the semi permeability film coating is by 5 parts of cellulose acetate, 0.6 part of diethyl phthalate and 0.4 part of VENLAFAXINE HCL controlled-release tablet preparation that polyethylene glycol 1500 is formed.
Embodiment six
The film-coated weight proportion of medicine label and semi permeability is the VENLAFAXINE HCL controlled-release tablet preparation of 1:0.03, wherein:
Consisting of of medicine label: 75 parts of VENLAFAXINE HCL, 112 parts of microcrystalline Cellulose, 5 parts of sodium chloride, 5 parts of 30 POVIDONE K 30 BP/USPs 30 and 2 parts of magnesium stearate.
Semi permeability is film-coated to consist of: 8 parts of cellulose acetate, 0.8 part of diethyl phthalate and 0.2 part of polyethylene glycol 1500.
The preparation method of above-mentioned VENLAFAXINE HCL controlled-release tablet preparation may further comprise the steps:
(1) preparation medicine label: VENLAFAXINE HCL, microcrystalline Cellulose, sodium chloride and the 30 POVIDONE K 30 BP/USP 30 of getting described proportioning, mix homogeneously, add 95% alcoholic solution and make soft material in right amount, cross 20 mesh sieves and granulate, dry under 50 ℃ of conditions, with 18 mesh sieve granulate, the magnesium stearate that adds described proportioning again, mixing, tabletting promptly makes the medicine label that contains VENLAFAXINE HCL;
(2) preparation coating solution: get cellulose acetate, diethyl phthalate and the polyethylene glycol 1500 of described proportioning, mix homogeneously, the acetone-alcoholic solution that adds an amount of volume ratio and be 4:1 be in right amount as the coating solvent, mixing, and it is standby to make coating solution;
(3) coating: the coating solution that the medicine label that makes of (1) step and (2) step are made places coating pan, coating to coating weightening finish part is about 3% of medicine label according to a conventional method, promptly make coated tablet,, obtain exsiccant coated tablet coated tablet under 40 ℃ of conditions dry 36 hours;
(4) punching: the aperture that to make a call to a diameter on the exsiccant coated tablet that makes in (3) step with laser or additive method be 0.2mm, promptly making the film-coated weight proportion of medicine label and semi permeability is 1:0.03, the medicine label is made up of 75 parts of VENLAFAXINE HCL, 112 parts of microcrystalline Cellulose, 5 parts of sodium chloride, 5 parts of 30 POVIDONE K 30 BP/USPs 30 and 2 parts of magnesium stearate, and the semi permeability film coating is by 8 parts of cellulose acetate, 0.8 part of diethyl phthalate and 0.2 part of VENLAFAXINE HCL controlled-release tablet preparation that polyethylene glycol 1500 is formed.
Embodiment seven
The film-coated weight proportion of medicine label and semi permeability is the VENLAFAXINE HCL controlled-release tablet preparation of 1:0.025, wherein:
Consisting of of medicine label: 75 parts of VENLAFAXINE HCL, 116 parts of microcrystalline Cellulose, 3 parts of sodium chloride, 7 parts of 30 POVIDONE K 30 BP/USPs 30 and 0.5 part of magnesium stearate.
Semi permeability is film-coated to consist of: 10 parts of cellulose acetate, 0.75 part of diethyl phthalate and 0.25 part of polyethylene glycol 1500.
The preparation method of above-mentioned VENLAFAXINE HCL controlled-release tablet preparation may further comprise the steps:
(1) preparation medicine label: VENLAFAXINE HCL, microcrystalline Cellulose, sodium chloride and the 30 POVIDONE K 30 BP/USP 30 of getting described proportioning, mix homogeneously, add 95% alcoholic solution and make soft material in right amount, cross 20 mesh sieves and granulate, dry under 50 ℃ of conditions, with 18 mesh sieve granulate, the magnesium stearate that adds described proportioning again, mixing, tabletting promptly makes the medicine label that contains VENLAFAXINE HCL;
(2) preparation coating solution: get cellulose acetate, diethyl phthalate and the polyethylene glycol 1500 of described proportioning, mix homogeneously, the acetone-water solution that adds an amount of volume ratio and be 20:1 be in right amount as the coating solvent, mixing, and it is standby to make coating solution;
(3) coating: the coating solution that the medicine label that makes of (1) step and (2) step are made places coating pan, coating to coating weightening finish part is about 2.5% of medicine label according to a conventional method, promptly make coated tablet,, obtain exsiccant coated tablet coated tablet under 40 ℃ of conditions dry 36 hours;
(4) punching: the aperture that to make a call to a diameter on the exsiccant coated tablet that makes in (3) step with laser or additive method be 0.5mm, promptly making the film-coated weight proportion of medicine label and semi permeability is 1:0.025, the medicine label is made up of 75 parts of VENLAFAXINE HCL, 116 parts of microcrystalline Cellulose, 3 parts of sodium chloride, 7 parts of 30 POVIDONE K 30 BP/USPs 30 and 0.5 part of magnesium stearate, and the semi permeability film coating is by 8 parts of cellulose acetate, 0.75 part of diethyl phthalate and 0.25 part of VENLAFAXINE HCL controlled-release tablet preparation that polyethylene glycol 1500 is formed.
Embodiment eight
The film-coated weight proportion of medicine label and semi permeability is the VENLAFAXINE HCL controlled-release tablet preparation of 1:0.035, wherein:
Consisting of of medicine label: 75 parts of VENLAFAXINE HCL, 114 parts of microcrystalline Cellulose, 4 parts of sodium chloride, 6.5 parts of 30 POVIDONE K 30 BP/USPs 30 and 2 parts of magnesium stearate.
Semi permeability is film-coated to consist of: 9 parts of cellulose acetate, 0.77 part of diethyl phthalate and 0.23 part of polyethylene glycol 1500.
The preparation method of above-mentioned VENLAFAXINE HCL controlled-release tablet preparation may further comprise the steps:
(1) preparation medicine label: VENLAFAXINE HCL, microcrystalline Cellulose, sodium chloride and the 30 POVIDONE K 30 BP/USP 30 of getting described proportioning, mix homogeneously, add 95% alcoholic solution and make soft material in right amount, cross 20 mesh sieves and granulate, dry under 50 ℃ of conditions, with 18 mesh sieve granulate, the magnesium stearate that adds described proportioning again, mixing, tabletting promptly makes the medicine label that contains VENLAFAXINE HCL;
(2) preparation coating solution: get cellulose acetate, diethyl phthalate and the polyethylene glycol 1500 of described proportioning, mix homogeneously, the acetone-water solution that adds an amount of volume ratio and be 15:1 be in right amount as the coating solvent, mixing, and it is standby to make coating solution;
(3) coating: the coating solution that the medicine label that makes of (1) step and (2) step are made places coating pan, coating to coating weightening finish part is about 3.5% of medicine label according to a conventional method, promptly make coated tablet,, obtain exsiccant coated tablet coated tablet under 45 ℃ of conditions dry 20 hours;
(4) punching: the aperture that to make a call to a diameter on the exsiccant coated tablet that makes in (3) step with laser or additive method be 0.7mm, promptly making the film-coated weight proportion of medicine label and semi permeability is 1:0.035, the medicine label is made up of 75 parts of VENLAFAXINE HCL, 114 parts of microcrystalline Cellulose, 4 parts of sodium chloride, 6.5 parts of 30 POVIDONE K 30 BP/USPs 30 and 2 parts of magnesium stearate, and the semi permeability film coating is by 9 parts of cellulose acetate, 0.77 part of diethyl phthalate and 0.23 part of VENLAFAXINE HCL controlled-release tablet preparation that polyethylene glycol 1500 is formed.
Embodiment nine
The film-coated weight proportion of medicine label and semi permeability is the VENLAFAXINE HCL controlled-release tablet preparation of 1:0.035, wherein:
Consisting of of medicine label: 75 parts of VENLAFAXINE HCL, 250 parts of dextrin, 1 part of potassium chloride, 20 parts of methylcellulose and 20 parts of magnesium stearate.
Semi permeability is film-coated to consist of: 12 parts of ethyl celluloses, 1 part of Macrogol 4000.
The preparation method of above-mentioned VENLAFAXINE HCL controlled-release tablet preparation may further comprise the steps:
(1) preparation medicine label: VENLAFAXINE HCL, dextrin, potassium chloride and the methylcellulose of getting described proportioning, mix homogeneously, add 95% alcoholic solution and make soft material in right amount, cross 20 mesh sieves and granulate, dry under 45 ℃ of conditions, with 18 mesh sieve granulate, the magnesium stearate that adds described proportioning again, mixing, tabletting promptly makes the medicine label that contains VENLAFAXINE HCL;
(2) preparation coating solution: get the ethyl cellulose and the Macrogol 4000 of described proportioning, mix homogeneously, the acetone-water solution that adds an amount of volume ratio and be 20:1 be in right amount as the coating solvent, mixing, and it is standby to make coating solution;
(3) coating: the coating solution that the medicine label that makes of (1) step and (2) step are made places coating pan, coating to coating weightening finish part is about 3.5% of medicine label according to a conventional method, promptly make coated tablet,, obtain exsiccant coated tablet coated tablet under 35 ℃ of conditions dry 30 hours;
(4) punching: the aperture that to make a call to a diameter on the exsiccant coated tablet that makes in (3) step with laser or additive method be 0.4mm, promptly making the film-coated weight proportion of medicine label and semi permeability is 1:0.035, the medicine label is made up of 75 parts of VENLAFAXINE HCL, 250 parts of dextrin, 1 part of potassium chloride, 20 parts of methylcellulose and 20 parts of magnesium stearate, and the semi permeability film coating is by 12 parts of ethyl celluloses and 1 part of VENLAFAXINE HCL controlled-release tablet preparation that Macrogol 4000 is formed.
Embodiment ten
The film-coated weight proportion of medicine label and semi permeability is the VENLAFAXINE HCL controlled-release tablet preparation of 1:0.03, wherein:
Consisting of of medicine label: 75 parts of VENLAFAXINE HCL, 30 parts of corn starchs, 20 parts of magnesium chlorides, 15 parts of sodium carboxymethyl cellulose and 15 parts of magnesium stearate.
Semi permeability is film-coated to consist of: 9 parts of cellulose propionates and 1 part of tartrate.
The preparation method of above-mentioned VENLAFAXINE HCL controlled-release tablet preparation may further comprise the steps:
(1) preparation medicine label: VENLAFAXINE HCL, corn starch, magnesium chloride and the sodium carboxymethyl cellulose of getting described proportioning, mix homogeneously, add 95% alcoholic solution and make soft material in right amount, cross 20 mesh sieves and granulate, dry under 50 ℃ of conditions, with 18 mesh sieve granulate, the magnesium stearate that adds described proportioning again, mixing, tabletting promptly makes the medicine label that contains VENLAFAXINE HCL;
(2) preparation coating solution: get the cellulose propionate and the tartrate of described proportioning, mix homogeneously, the methylene chloride-methanol solution solution that adds an amount of volume ratio and be 10:1 be in right amount as the coating solvent, mixing, and it is standby to make coating solution;
(3) coating: the coating solution that the medicine label that makes of (1) step and (2) step are made places coating pan, coating to coating weightening finish part is about 3% of medicine label according to a conventional method, promptly make coated tablet,, obtain exsiccant coated tablet coated tablet under 40 ℃ of conditions dry 24 hours;
(4) punching: the aperture that to make a call to a diameter on the exsiccant coated tablet that makes in (3) step with laser or additive method be 0.8mm, promptly making the film-coated weight proportion of medicine label and semi permeability is 1:0.03, the medicine label is made up of 75 parts of VENLAFAXINE HCL, 30 parts of corn starchs, 20 parts of magnesium chlorides, 15 parts of sodium carboxymethyl cellulose and 15 parts of magnesium stearate, and the semi permeability film coating is by 9 parts of cellulose propionates and 1 part of VENLAFAXINE HCL controlled-release tablet preparation that tartrate is formed.
Embodiment 11
The film-coated weight proportion of medicine label and semi permeability is the VENLAFAXINE HCL controlled-release tablet preparation of 1:0.05, wherein:
Consisting of of medicine label: 75 parts of VENLAFAXINE HCL, 100 portions of mannitol, 50 parts of potassium sulfate, 10 parts of carboxy-propyl cellulose sodium and 1 part of magnesium stearate.
Semi permeability is film-coated to consist of: 6 parts of Merlon and 1 part of adipate ester.
The preparation method of above-mentioned VENLAFAXINE HCL controlled-release tablet preparation may further comprise the steps:
(1) preparation medicine label: VENLAFAXINE HCL, mannitol, potassium sulfate and the carboxy-propyl cellulose sodium of getting described proportioning, mix homogeneously, add 95% alcoholic solution and make soft material in right amount, cross 20 mesh sieves and granulate, dry under 50 ℃ of conditions, with 18 mesh sieve granulate, the magnesium stearate that adds described proportioning again, mixing, tabletting promptly makes the medicine label that contains VENLAFAXINE HCL;
(2) preparation coating solution: get the Merlon and the adipate ester of described proportioning, mix homogeneously, the methylene chloride-methanol solution solution that adds an amount of volume ratio and be 10:1 be in right amount as the coating solvent, mixing, and it is standby to make coating solution;
(3) coating: the coating solution that the medicine label that makes of (1) step and (2) step are made places coating pan, coating to coating weightening finish part is about 5% of medicine label according to a conventional method, promptly make coated tablet,, obtain exsiccant coated tablet coated tablet under 40 ℃ of conditions dry 24 hours;
(4) punching: the aperture that to make a call to two diameters on the exsiccant coated tablet that makes in (3) step with laser or additive method be 0.2mm, promptly making the film-coated weight proportion of medicine label and semi permeability is 1:0.05, the medicine label is made up of 75 parts of VENLAFAXINE HCL, 100 portions of mannitol, 50 parts of potassium sulfate, 10 parts of carboxy-propyl cellulose sodium and 1 part of magnesium stearate, and the semi permeability film coating is by 6 parts of Merlon and 1 part of VENLAFAXINE HCL controlled-release tablet preparation that adipate ester is formed.
Embodiment 12
The film-coated weight proportion of medicine label and semi permeability is the VENLAFAXINE HCL controlled-release tablet preparation of 1:0.02, wherein:
Consisting of of medicine label: 75 parts of VENLAFAXINE HCL, 100 parts of sorbitol, 100 parts of lactose, 4 parts of magnesium sulfate, 1 part of water and 0.1 part of magnesium stearate.
Semi permeability is film-coated to consist of: 5 parts of polyvinyl alcohol, 0.5 part of phosphate ester and 0.5 part of succinate.
The preparation method of above-mentioned VENLAFAXINE HCL controlled-release tablet preparation may further comprise the steps:
(1) preparation medicine label: VENLAFAXINE HCL, sorbitol, lactose, magnesium sulfate and the water of getting described proportioning, mix homogeneously, add 95% alcoholic solution and make soft material in right amount, cross 20 mesh sieves and granulate, dry under 50 ℃ of conditions, with 18 mesh sieve granulate, the magnesium stearate that adds described proportioning again, mixing, tabletting promptly makes the medicine label that contains VENLAFAXINE HCL;
(2) preparation coating solution: get polyvinyl alcohol, phosphate ester and the succinate of described proportioning, mix homogeneously, the methylene chloride-methanol solution solution that adds an amount of volume ratio and be 10:1 be in right amount as the coating solvent, mixing, and it is standby to make coating solution;
(3) coating: the coating solution that the medicine label that makes of (1) step and (2) step are made places coating pan, coating to coating weightening finish part is about 2% of medicine label according to a conventional method, promptly make coated tablet,, obtain exsiccant coated tablet coated tablet under 40 ℃ of conditions dry 24 hours;
(4) punching: the aperture that to make a call to a diameter on the exsiccant coated tablet that makes in (3) step with laser or additive method be 1.0mm, promptly making the film-coated weight proportion of medicine label and semi permeability is 1:0.02, the medicine label is made up of 75 parts of VENLAFAXINE HCL, 100 parts of sorbitol, 100 parts of lactose, 4 parts of magnesium sulfate, 1 part of water and 0.1 part of magnesium stearate, and the semi permeability film coating is by 5 parts of polyvinyl alcohol, 0.5 part of phosphate ester and 0.5 part of VENLAFAXINE HCL controlled-release tablet preparation that succinate is formed.
Embodiment 13
The film-coated weight proportion of medicine label and semi permeability is the VENLAFAXINE HCL controlled-release tablet preparation of 1:0.04, wherein:
Consisting of of medicine label: 75 parts of VENLAFAXINE HCL, 114 portions of sucrose, 30 parts of sodium sulfate, 6 part of 95% alcoholic solution and 10 parts of magnesium stearate.
Semi permeability is film-coated to consist of: 15 parts of vinylacetates and 1 part of glyceride.
The preparation method of above-mentioned VENLAFAXINE HCL controlled-release tablet preparation may further comprise the steps:
(1) preparation medicine label: VENLAFAXINE HCL, sucrose, sodium sulfate and 95% alcoholic solution of getting described proportioning, mix homogeneously, make soft material, cross 20 mesh sieves and granulate, dry under 50 ℃ of conditions, with 18 mesh sieve granulate, the magnesium stearate that adds described proportioning again, mixing, tabletting promptly makes the medicine label that contains VENLAFAXINE HCL;
(2) preparation coating solution: get the vinylacetate and the glyceride of described proportioning, mix homogeneously, the methylene chloride-methanol solution solution that adds an amount of volume ratio and be 10:1 be in right amount as the coating solvent, mixing, and it is standby to make coating solution;
(3) coating: the coating solution that the medicine label that makes of (1) step and (2) step are made places coating pan, coating to coating weightening finish part is about 4% of medicine label according to a conventional method, promptly make coated tablet,, obtain exsiccant coated tablet coated tablet under 40 ℃ of conditions dry 24 hours;
(4) punching: the aperture that to make a call to a diameter on the exsiccant coated tablet that makes in (3) step with laser or additive method be 0.6mm, promptly making the film-coated weight proportion of medicine label and semi permeability is 1:0.04, the medicine label is made up of 75 parts of VENLAFAXINE HCL, 114 portions of sucrose, 30 parts of sodium sulfate, 6 part of 95% alcoholic solution and 10 parts of magnesium stearate, and the semi permeability film coating is by 15 parts of vinylacetates and 1 part of VENLAFAXINE HCL controlled-release tablet preparation that glyceride is formed.
Claims (11)
1. VENLAFAXINE HCL controlled-release tablet preparation, constitute by medicine label that comprises VENLAFAXINE HCL and the semi permeability film coating that has aperture, it is characterized in that the medicine label is made up of 75 parts of VENLAFAXINE HCL, 30-250 part filler, 1-50 part osmotic pressure promoter, 1-20 part binding agent and 0.1-20 part lubricant; The semi permeability film coating is made up of 5-15 part semipermeable membrane coating material and 1 part of plasticizer;
Described osmotic pressure promoter is meant any one or more than one the mixture in potassium chloride, sodium chloride, magnesium chloride, potassium sulfate, sodium sulfate, the magnesium sulfate: filler is meant any one or more than one the mixture in microcrystalline Cellulose, dextrin, starch, mannitol, sorbitol, lactose, the sucrose; Binding agent is meant any one or more than one the mixture in the mixed solution of polyvidone, methylcellulose, sodium carboxymethyl cellulose, carboxylic propyl methocel, water, water and alcohol; Lubricant is meant magnesium stearate; The semipermeable membrane coating material is meant any one or more than one the mixture in cellulose acetate, ethyl cellulose, cellulose propionate, Merlon, polyethylene, polyvinyl alcohol, the vinylacetate; Plasticizer is meant any one or more than one the mixture of phthalate, glyceride, succinate, benzoate, phosphate ester, adipate ester, tartrate, Polyethylene Glycol apoplexy due to endogenous wind.
2. VENLAFAXINE HCL controlled-release tablet preparation according to claim 1 is characterized in that: described osmotic pressure promoter is meant any one or more than one the mixture in potassium chloride, sodium chloride, the magnesium chloride; Filler is meant microcrystalline Cellulose; Plasticizer is meant any one or more than one the mixture in diethyl phthalate, polyethylene glycol 1500 or the Macrogol 4000.
3. VENLAFAXINE HCL controlled-release tablet preparation according to claim 2 is characterized in that: described medicine label is made up of 75 parts of VENLAFAXINE HCL, 30-250 part microcrystalline Cellulose, 1-50 part sodium chloride, 1-20 part 30 POVIDONE K 30 BP/USP 30 and 0.1-20 part magnesium stearate: the semi permeability film coating is made up of 5-15 part cellulose acetate, 0.6-0.9 part diethyl phthalate and 0.1-0.4 part polyethylene glycol 1500.
4. VENLAFAXINE HCL controlled-release tablet preparation according to claim 3 is characterized in that: described medicine label is made up of 75 parts of VENLAFAXINE HCL, 100-120 part microcrystalline Cellulose, 1-30 part sodium chloride, 1-15 part 30 POVIDONE K 30 BP/USP 30 and 0.1-10 part magnesium stearate; The semi permeability film coating is made up of 6-12 part cellulose acetate, 0.6-0.9 part diethyl phthalate and 0.1-0.4 part polyethylene glycol 1500.
5. VENLAFAXINE HCL controlled-release tablet preparation according to claim 4 is characterized in that: described medicine label is made up of 75 parts of VENLAFAXINE HCL, 112-116 part microcrystalline Cellulose, 3-5 part sodium chloride, 5-7 part 30 POVIDONE K 30 BP/USP 30 and 0.5-2 part magnesium stearate; The semi permeability film coating is made up of 8-10 part cellulose acetate, 0.75-0.80 part diethyl phthalate and 0.20-0.25 part polyethylene glycol 1500.
6. VENLAFAXINE HCL controlled-release tablet preparation according to claim 5 is characterized in that: described medicine label is made up of 75 parts of VENLAFAXINE HCL, 114 parts of microcrystalline Cellulose, 4 parts of sodium chloride, 6 parts of 30 POVIDONE K 30 BP/USPs 30 and 1 part of magnesium stearate; The semi permeability film coating is made up of 9 parts of cellulose acetate, 0.78 part of diethyl phthalate and 0.22 part of polyethylene glycol 1500.
7. VENLAFAXINE HCL controlled-release tablet preparation according to claim 1 is characterized in that: described medicine label and the film-coated weight proportion of semi permeability are 1:0.02-0.05.
8. VENLAFAXINE HCL controlled-release tablet preparation according to claim 7 is characterized in that: described medicine label and the film-coated weight proportion of semi permeability are 1:0.03-0.04.
9. VENLAFAXINE HCL controlled-release tablet preparation according to claim 1 is characterized in that: with laser or additive method preparation one or more small delivery aperture are arranged on the semi permeability film coating of described preparation.
10. the preparation method of each described VENLAFAXINE HCL controlled-release tablet preparation among the claim 1-9 may further comprise the steps:
(1) preparation medicine label: get VENLAFAXINE HCL, filler, osmotic pressure promoter and the binding agent of described proportioning, mix homogeneously is granulated according to a conventional method, the lubricant that adds described proportioning again, mixing, tabletting promptly makes the medicine label that contains VENLAFAXINE HCL;
(2) preparation coating solution: get the semipermeable membrane coating material and the plasticizer of described proportioning, mix homogeneously adds an amount of coating solvent, mixing, and it is standby to make coating solution;
(3) coating: the coating solution that the medicine label that makes of (1) step and (2) step are made places coating pan, and coating makes coated tablet according to a conventional method, and coated tablet is dry under 30-60 ℃ of condition, obtains exsiccant coated tablet;
(4) punch: go on foot on the exsiccant coated tablet that makes in (3) with laser or additive method and beat the aperture that one or more diameters are 0.2-1.0mm, promptly make the VENLAFAXINE HCL controlled-release tablet preparation.
11. the preparation method of VENLAFAXINE HCL controlled-release tablet preparation according to claim 10 is characterized in that: the coating solvent described in (2) step is that volume ratio is acetone-water solution or the acetone-alcoholic solution of 4-20:1; (4) aperture described in the step is one, and its diameter is 0.4-0.8mm.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2004100906563A CN100463676C (en) | 2004-11-11 | 2004-11-11 | Control releasing venlafaxine hydrochloride tablet and its prepn |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2004100906563A CN100463676C (en) | 2004-11-11 | 2004-11-11 | Control releasing venlafaxine hydrochloride tablet and its prepn |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1771921A CN1771921A (en) | 2006-05-17 |
| CN100463676C true CN100463676C (en) | 2009-02-25 |
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| CNB2004100906563A Active CN100463676C (en) | 2004-11-11 | 2004-11-11 | Control releasing venlafaxine hydrochloride tablet and its prepn |
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| CN100584319C (en) | 2006-10-16 | 2010-01-27 | 北京科信必成医药科技发展有限公司 | Multiple apertures releasing osmosis pump control release tablet and preparation process thereof |
| CN104784145B (en) * | 2015-04-30 | 2017-11-21 | 海安苏博机器人科技有限公司 | A kind of venlafaxine sustained-release preparations and preparation method thereof |
| CN112999179B (en) * | 2019-12-20 | 2024-02-23 | 成都康弘药业集团股份有限公司 | Pharmaceutical composition containing venlafaxine hydrochloride |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1164389A (en) * | 1996-03-25 | 1997-11-12 | 美国家用产品公司 | Extended release formulation |
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2004
- 2004-11-11 CN CNB2004100906563A patent/CN100463676C/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1164389A (en) * | 1996-03-25 | 1997-11-12 | 美国家用产品公司 | Extended release formulation |
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Owner name: CHENGDU KANGHONG MEDICINE GROUP CO.LTD. Free format text: FORMER OWNER: CHENGDU KANGHONG TECHNOLOGY INDUSTRIAL (GROUP) CO., LTD. Effective date: 20081010 |
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Effective date of registration: 20081010 Address after: 36, Shu West Road, Sichuan, Chengdu, Jinniu District, China: 610036 Applicant after: Chengdu Kanghong Pharmaceuticals Group Co., Ltd. Address before: 36, Shu West Road, Sichuan, Chengdu, Jinniu District, China: 610036 Applicant before: Chengdu Kanghong Sci-Tech Industry (Group) Co., Ltd. |
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