CN102641255A - Febuxostat osmotic pump controlled release tablet for treating gout and preparation method - Google Patents
Febuxostat osmotic pump controlled release tablet for treating gout and preparation method Download PDFInfo
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- CN102641255A CN102641255A CN2012101406761A CN201210140676A CN102641255A CN 102641255 A CN102641255 A CN 102641255A CN 2012101406761 A CN2012101406761 A CN 2012101406761A CN 201210140676 A CN201210140676 A CN 201210140676A CN 102641255 A CN102641255 A CN 102641255A
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- febuxostat
- controlled release
- osmotic pump
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Abstract
The invention relates to a medical preparation containing a Febuxostat compound and with special physical shape as a characteristic, in particular to a Febuxostat osmotic pump controlled release tablet for treating gout. The osmotic pump controlled release agent comprises a core tablet and a coat and is characterized in that the core tablet is composed of the following components by weight: 10% to 40% of Febuxostat, 30% to 60% of osmotic pressure active substance, 4% to 20% of alkaline substance, 0% to 30% of filler, 1% to 5% of adhesive and 0.2% to 2% of lubricant. The coat is composed of the following components by weight: 40% to 70% of cellulose acetate, 20% to 40% of polyethylene glycol 400 and 10% to 20% of phthalic acid diethyl ester. The tablet resolves the problem that the Febuxostat is slightly soluble medicine and is hard to release by adding the alkaline substance into the core tablet, is capable of releasing over 90% of medicine within 12 hours by screening optimization of film formation materials, porogen and plasticizers in the coat, and satisfies zero level dynamic medicine releasing characteristics. The Febuxostat osmotic pump controlled release tablet for treating gout can be used for treating gout and has the advantages of being durable in effect, safe and easy to produce and prepare.
Description
Technical field
What the present invention relates to contain the Febuxostat chemical compound is shaped as the pharmaceutical product of characteristic with specific physical, is specifically related to a kind of Febuxostat osmotic pump controlled release tablet of treating the treatment gout of goat.
Background technology
Gout is a kind ofly to cause the arthropathy of blood uric acid due to increasing because of purine metabolic disturbance.Urate crystal is deposited in the joint tissue will produce tophus, and the joint is produced irreversible infringement, causes joint deformity or dysfunction.The maximum harm of gout is to cause renal damage, and severe patient can be died from renal failure.Sickness rate is lower before the gout, is called as " affluenza ", but in recent years, along with the change of life style and dietary structure, gout rises at the sickness rate straight line of China, and sickness rate present and diabetes are very nearly the same.According to statistics, gout in the many metropolitan adult males of China sickness rate near 30%.The existing kind of antigout drug is few; Clinical treatment is main with colchicine, nonsteroidal antiinflammatory drug, hormone, promotion urate excretion medicine (like probenecid, sulfinpyrazone) and inhibition uric acid synthetic drug (allopurinol) mainly; These medicines are defectiveness all in treatment, and weak curative effect, side effect become the bottleneck of its clinical practice greatly.Therefore, novel anti-gout drugs is one of focus of global new drug development in recent years.
The chemistry of Febuxostat (Febuxostat) is called 2-[3-cyano-4-isobutoxy phenyl]-4-methylthiazol-5-formic acid; Shown in the following formula I of structural formula; It is a kind of brand-new efficient non-purine class selectivity xanthine oxidase inhibitor, can be used for treating the too high gout of uric acid clinically.In February, 2009, FDA has ratified the Febuxostat (trade name Uloric) of Japanese Tap Pharmaceutical Products (US), and this is first medicine that obtains the treatment hyperuricemia of FDA approval over nearly 40 years.Compare with the standard care medicine allopurinol of present gout; Febuxostat is with the obvious advantage: the former only has inhibitory action to the xanthine oxidoreductase enzyme of reproducibility; And Febuxostat all has significant inhibitory effect for the xanthine oxidoreductase enzyme of oxidized form and reduced form; So its uric acid resisting effect is more powerful, and owing to do not relate to the metabolism of purine and pyrimidine, and have better safety.
Gout is a kind of chronic disease, needs long-term (generally reaching more than half a year) to take medicine, and drug withdrawal or vivo medicine concentration are low during the treatment might cause that all uric acid raises once again in the blood, thereby causes the gout recurrence.If can guarantee that blood samples of patients Chinese medicine concentration steadily, lastingly, helps the control of uric acid with ten minutes, even might shorten treatment cycle.The osmotic pump controlled-releasing technology is a kind of novel medicament preparation means, can make preparation discharge medicine with the zero order kinetics characteristic in vivo, thereby can keep patient's blood Chinese medicine for a long time in the treatment concentration range.Because controlled releasing penetrant pump is to be release power with the osmotic pressure, rate of releasing drug does not receive the influence of factors such as gastrointestinal tract pH value, food, gastric emptying time, and the inside and outside dependency is good, is a kind of comparatively ideal controlled release formulations for oral administration.At present, Febuxostat has only conventional tablet (specification is 40mg and 80mg) clinical practice, and the development of the Febuxostat osmotic pump controlled release tablet of treatment gout is significant for the therapeutic effect that improves this medicine.
The basic structure of osmotic pumps is earlier medicine and proper auxiliary materials to be pressed into label, and the semipermeable polymer clothing of outsourcing one deck film is opened a small delivery aperture with laser on the clothing film.Oral back gastrointestinal moisture sees through semipermeable membrane and gets into label; Make medicine be dissolved into saturated solution, solution becomes hyperosmotic solution in the film because of the osmotic pressure active substance makes, thereby makes moisture continue to get in the film; Drug solution pumps from aperture, and medicine is discharged into outside the sheet with constant speed.The osmotic pump tablet shortcoming that this method makes is that laser boring might or differ the aperture with the film calcination, and duct, oral back is prone at gastrointestinal tract blocked and cause random release.In recent years, be employed in more and add porogen (water-soluble substances) in the filmogen, improve the permeability of film; Process the pore type osmotic pump tablet, avoided the problems referred to above, also simplified preparation technology; Be more suitable for industrialized great production, so the Febuxostat pore type osmotic pump controlled release tablet fully of drawing up.
Although more existing research reports about other drug pore type osmotic pump tablet; But different drug; Because the physicochemical property different needs is selected adjuvant and consumptions such as different osmotic pressure active substances, porogen, plasticizer for use; So the technical problem that the preparation of Febuxostat pore type osmotic pump controlled release tablet still has many needs to overcome and solve has only the specific technical scheme of employing could realize that Febuxostat continues release with zero level speed.
Summary of the invention
Technical problem to be solved by this invention provides a kind of Febuxostat osmotic pump controlled release tablet of treating gout, and this osmotic pump controlled release tablet can be steadily, sustained release, meets the requirement of treatment gout to blood Chinese medicine concentration.
The technical scheme that the present invention overcomes the above problems is described below:
A kind of Febuxostat osmotic pump controlled release tablet of treating gout, this osmotic pump controlled release tablet comprises label and coating, it is characterized in that; Described label is made up of following components in weight percentage: Febuxostat 10 ~ 40%; Osmotic pressure active substance 30 ~ 60%, alkaline matter 4 ~ 20%, filler 0 ~ 30%; Adhesive 1 ~ 5%, lubricant 0.2 ~ 2%; Described coating is made up of following components in weight percentage: cellulose acetate 40 ~ 70%, PEG400 20 ~ 40%, diethyl phthalate 10 ~ 20%; Wherein,
Described osmotic pressure active substance is one or both the mixture in lactose, glucose, mannitol and the sodium chloride;
Described alkaline matter is sodium carbonate or sodium hydroxide;
Described filler is microcrystalline Cellulose, pre-paying starch or dextrin;
Described adhesive is hypromellose, polyvidone or starch;
Described lubricant is one or both the mixture in magnesium stearate, micropowder silica gel and the Pulvis Talci.
As preferably, said alkaline matter is a sodium carbonate, and the content in label is 10 ~ 15%.
As preferably, the content of said PEG400 in coating is 25 ~ 35%.
A kind of Febuxostat osmotic pump controlled release tablet of treating gout of the present invention, the method for preparing of this osmotic pump controlled release tablet is made up of following steps:
With Febuxostat, osmotic pressure active substance, alkaline matter and after filler mixes, add the aqueous solution of adhesive, by hand or mixer mix homogeneously system soft material; 16 or 18 mesh sieves are granulated, and are dry under 60 ℃, 14 or 16 mesh sieve granulate; Add lubricant, mix, be pressed into label with tablet machine; The aqueous solution that the aqueous solution of wherein said adhesive is is 10 ~ 50mg/ml with the adhesive concentration that is mixed with soluble in water;
Get cellulose acetate, PEG400 and diethyl phthalate and be dissolved in the acetone, compound concentration is the acetone coating solution of 40 ~ 80mg/ml;
Above-mentioned label is placed coating in the coating pan, and making described label weightening finish is 3 ~ 7%, in 40 ℃ of dryings, the clothing film is solidified behind the coating, promptly gets the Febuxostat osmotic pump controlled release tablet of treating gout.
The present invention has solved the problem that the insoluble drug Febuxostat is difficult to discharge through in label, adding alkaline matter; And through screening and optimizing to the filmogen in the coating, porogen and plasticizer; Can make the interior medicine that discharges more than 90% of Febuxostat osmotic pump controlled release tablet 12h of treatment gout, and the fit zero-order drug release characteristic.The Febuxostat osmotic pump controlled release tablet of treatment gout of the present invention can be used for the treatment of goat, has the effect of holding, safety and is easy to produce the advantage of preparation.
The beneficial effect of the said osmotic pump controlled release tablet of the invention described above is confirmed by following experiment.
One, label neutral and alkali material is to the influence of Febuxostat release degree
The dissolubility of Febuxostat in water is very little; Under the situation of not disintegrate of preparation, be difficult to stripping; And osmotic pump controlled release tablet is the film controlling type preparation, does not add disintegrating agent in the label and disintegrate can not take place, and therefore adopts the Febuxostat osmotic pump controlled release tablet medicine of conventional way preparation treatment gout to be difficult to discharge.The inventor has carried out a large amount of research to the dissolubility of Febuxostat under water environment for this reason; The Febuxostat dissolubility that the result finds to contain carboxyl raises with the pH of reaction system to be increased; It is almost insoluble when pH value is 3.0 ~ 5.0; Soluble,very slightly when pH value is 6.0 ~ 8.0, slightly soluble when pH value is 9.0.Although the dissolubility of Febuxostat is still less under high pH value,, rate of releasing drug and rate of dissolution can guarantee that still Febuxostat continues, release stably in case reaching balance.Based on this principle, in label, behind the adding alkaline matter, can make Febuxostat osmotic pump controlled release tablet 12h discharge medicine and reach more than 90%, and the fit zero-order drug release characteristic.
The release degree that Febuxostat osmotic pump controlled release tablet and this prescription of embodiment 1 prepared treatment gout removed the constant osmotic pump controlled release tablet that makes of all the other adjuvants of sodium carbonate compares.Release degree inspection method is: get these article, according to dissolution method (two appendix X of Chinese Pharmacopoeia version in 2010 C, second method), (get 0.2mol/L potassium dihydrogen phosphate 250ml with phosphate buffer (pH 6.8); Add 0.2mol/L sodium hydroxide solution 118ml, be diluted with water to 1000ml, shake up; Promptly getting) 900ml is dissolution medium, the rotating speed of dissolution appearance slurry is that per minute 50 changes, operation in accordance with the law; Respectively at 1,2,3,4,6,8,10, the 12h 5ml that takes a sample; Replenish isothermal equal-volume blank medium simultaneously, sample is got subsequent filtrate with shining ultraviolet visible spectrophotometry (two appendix IV of Chinese Pharmacopoeia version in 2010 A) through 0.45 μ m filtering with microporous membrane; Wavelength at 314nm is measured absorbance, presses C
16H
16N
2O
3The absorptance of S
Be that 754 calculating cumulative discharge percentage rate, the result is as shown in Figure 1.Do not differ greatly with the release profiles that adds alkaline matter by not adding alkaline matter in the visible label of Fig. 1; The medicine that does not add in the Febuxostat osmotic pump controlled release tablet of alkaline matter almost can discharge; After adding alkaline matter, can make Febuxostat osmotic pump controlled release tablet 12 h discharge medicine and reach more than 90%.
Two, the screening of coating material
Because osmotic pump controlled release tablet is the film controlling type preparation, coating is bigger to the influence of the Febuxostat osmotic pump controlled release tablet release of treatment gout, so need coating material be comprised: filmogen, porogen and plasticizer screen.Press embodiment 1 prescription preparation label, adopt experiment of single factor that coating material is screened, specific as follows:
1. the screening of filmogen: fixing PEG400 with 25% is a porogen in the coating prescription; 12.5% diethyl phthalate is a plasticizer; Be that filmogen carries out coating with 62.5% cellulose acetate or ethyl cellulose respectively; The Febuxostat osmotic pump controlled release tablet of the different treatment gout of two kinds of filmogens; Adopt said method to measure releases degree, the result sees Fig. 2, obviously is the Febuxostat osmotic pump controlled release tablet release effect ideal comparatively of the treatment gout that makes of filmogen with the cellulose acetate.
2. the screening of porogen: fixing cellulose acetate with 62.5% is a filmogen in the coating prescription; 12.5% diethyl phthalate is a plasticizer; Be that porogen carries out coating with 25% PEG400, Macrogol 2000 and hypromellose respectively; The Febuxostat osmotic pump controlled release tablet of the different treatment gout of three kinds of porogen; Adopt said method to measure the release degree, the result sees Fig. 3, is that the Febuxostat osmotic pump controlled release tablet release effect of the treatment gout that makes of porogen is ideal with the PEG400.
3. plastifying screening: fixing cellulose acetate with 62.5% is a filmogen in the coating prescription; 25% PEG400 is a porogen; Be that plasticizer carries out coating with 12.5% triethyl citrate, diethyl phthalate, dibutyl phthalate respectively; The Febuxostat osmotic pump controlled release tablet of the different treatment gout of three kinds of plasticizers; Adopt said method to measure the release degree, the result sees Fig. 4, is that the Febuxostat osmotic pump controlled release tablet release effect of the treatment gout that makes of plasticizer is ideal with the diethyl phthalate.
According to above experimental result, preferred cellulose acetate is that filmogen, PEG400 are that porogen, diethyl phthalate are plasticizer.
Three, dosage confirms
The inventor adopts rat to investigate the absorption dynamics of Febuxostat in rat preduodenal, jejunum, ileum and colon at the unidirectional intestinal perfusion of body model.The accurate Febuxostat stock solution (10mmol/L) of drawing uses the HBSS buffer to dilute to such an extent that concentration is the test liquid of 5,10,20 μ mol/L, and is subsequent use.Rat overnight fasting (freely drinking water) before the art, the anesthesia of lumbar injection urethane solution, fixing, and keep 37 ℃ of body temperature.Along ventrimeson otch 4cm, open the abdominal cavity, near duodenum place ligation bile duct, insert polyethylene tube at duodenum, jejunum, ileum and colon two ends respectively, to prick with toe-in and fix, otch covers to preserve moisture with the gauze that is soaked with normal saline.After using the normal saline that is preheated to 37 ℃ that intestinal contents is rinsed well, get confession reagent liquid with 10mLh
-1The flow velocity perfusion, every behind the balance 30min, and accurately claim constant current fluid quality at a distance from 30min Fractional Collections perfusate (collecting altogether 4 times).When collecting each intestinal segment perfusate, collect blank perfusate without intestinal, precise weighing is to proofread and correct the influence of change of soil water content to drug level.Experiment is measured each intestinal segment length after finishing, and adopts the Ultra Performance Liquid Chromatography method to measure perfusate Chinese medicine concentration, and calculates the absorbance (R of Febuxostat at each intestinal segment
a), effective infiltration coefficient (P of reflection overall penetration situation
Eff), and get rid of medicine in the water layer diffusion influence, show its intestinal infiltration coefficient (P through the actual penetrating power of intestinal mucosa
w).Result's (seeing table 1) show Febuxostat in the absorption rate of duodenum and colon apparently higher than ileum and jejunum, all better in the absorption of whole intestinal (4 sections intestinal), intestinal infiltration coefficient (P
w) value is 0.96 ~ 16.78 (to it has been generally acknowledged that the P of chemical compound
wValue absorbed good greater than 1 o'clock).
Table 1 variable concentrations Febuxostat is in the absorption parameter value (n=6) of the different intestinal segments of rat
Therefore, for the oral administration of Febuxostat, absorbing is not rate-limiting step, as long as its controlled release preparation can be kept blood drug level steadily, lastingly by constant speed release medicine.Daily dose (the X of Febuxostat ordinary tablet
0) be 40 ~ 80mg, eliminate half-life (t
1/2) being about 6.5h, the dosage of its controlled release preparation should be X
0* (0.693/t
1/2) * 12h, this day is taken the osmotic pump controlled release tablet that contains Febuxostat 50 ~ 100mg, can realize it and keep effective blood drug concentration and reach more than the 12h.
Description of drawings
Fig. 1 is the release that adds or do not add the Febuxostat osmotic pump controlled release tablet of the treatment gout that alkaline matter the makes line of writing music; Wherein,
expression release of adding alkaline matter line of writing music; The release that
expression does not the add alkaline matter line of writing music.
The release of the Febuxostat osmotic pump controlled release tablet of the treatment gout that Fig. 2 makes for the different filmogens line of writing music; Wherein,
expression is the release of the filmogen line of writing music with the cellulose acetate;
expression is the release of the filmogen line of writing music with the ethyl cellulose.
The release of the Febuxostat osmotic pump controlled release tablet of the treatment gout that Fig. 3 makes for the different porogen line of writing music; Wherein,
expression is the release of the porogen line of writing music with the PEG400;
expression is the release of the porogen line of writing music with the Macrogol 2000;
expression is the release of the porogen line of writing music with the hypromellose.
The release of the Febuxostat osmotic pump controlled release tablet of the treatment gout that Fig. 4 makes for the different plasticizers line of writing music; Wherein,
expression is the release of the porogen line of writing music with the triethyl citrate;
expression is the release of the porogen line of writing music with the diethyl phthalate;
expression is the release of the porogen line of writing music with the dibutyl phthalate.
Fig. 5 is the release of Febuxostat osmotic pump controlled release tablet of the treatment gout of embodiment 2, embodiment 3, embodiment 4 line of writing music; Wherein, the release line of writing music of
expression embodiment 2; The release line of writing music of
expression embodiment 3; The release line of writing music of
expression embodiment 4.
The specific embodiment
Embodiment 1
Prescription:
Method for making: got 80 purpose Febuxostats, lactose, sodium chloride, sodium carbonate and microcrystalline Cellulose mixing, adding concentration is 4% hypromellose aqueous solution, with mixer mix homogeneously system soft material; 16 mesh sieves are granulated; In 60 ℃ of dryings, 14 mesh sieve granulate add magnesium stearate and micropowder silica gel; Mixing, tabletting.Getting cellulose acetate, PEG400 and diethyl phthalate, is solvent preparation coating solution with 500ml acetone.Above-mentioned label is placed coating in the coating pan, and the coating weightening finish is 5% of label weight, and aging 12h in the rearmounted 40 ℃ of baking ovens of coating promptly gets, and every contains Febuxostat 50mg.Oral 1 ~ 2 of every day.Adopt said method that the release degree of the Febuxostat osmotic pump controlled release tablet of prepared treatment gout is detected, (see figure 1) fit zero-order drug release characteristic (correlation coefficient r is 0.988) as a result, 12h cumulative release percentage rate reaches 91.6%.
Prescription:
The label prescription:
Coating prescription (the coating weightening finish is 7% of label weight):
Method for making: got 80 purpose Febuxostats, mannitol, sodium chloride, sodium hydroxide and pre-paying starch mixing, adding concentration is 5% starch slurry, with mixer mix homogeneously system soft material; 18 mesh sieves are granulated, in 60 ℃ of dryings, and 16 mesh sieve granulate; Add magnesium stearate, mixing, tabletting.Getting cellulose acetate, PEG400 and diethyl phthalate, is solvent preparation coating solution with 500ml acetone.Above-mentioned label is placed coating in the coating pan, and the coating weightening finish is 7% of label weight, and aging 12h in the rearmounted 40 ℃ of baking ovens of coating promptly gets, and every contains Febuxostat 25mg.Oral 2 ~ 4 of every day.Adopt said method that the release degree of the Febuxostat osmotic pump controlled release tablet of prepared treatment gout is detected, it is (see figure 5) fit zero-order drug release characteristic (correlation coefficient r is 0.986) as a result, and 12h cumulative release percentage rate reaches 94.4%.
Embodiment 3
Prescription:
The label prescription:
Coating prescription (the coating weightening finish is 5% of label weight):
Method for making: got 80 purpose Febuxostats, glucose, sodium chloride, sodium carbonate and dextrin mixing, adding concentration is 5% polyvidone aqueous solution, mix homogeneously system soft material by hand; 16 mesh sieves are granulated, in 60 ℃ of dryings, and 14 mesh sieve granulate; Add magnesium stearate and Pulvis Talci, mixing, tabletting.Getting cellulose acetate, PEG400 and diethyl phthalate, is solvent preparation coating solution with 500ml acetone.Above-mentioned label is placed coating in the coating pan, and the coating weightening finish is 5% of label weight, and aging 12h in the rearmounted 40 ℃ of baking ovens of coating promptly gets, and every contains Febuxostat 50mg.Oral 1 ~ 2 of every day.Adopt said method that the release degree of the Febuxostat osmotic pump controlled release tablet of prepared treatment gout is detected, it is (see figure 5) fit zero-order drug release characteristic (correlation coefficient r is 0.993) as a result, and 12h cumulative release percentage rate reaches 90.7%.
Prescription:
The label prescription:
Coating prescription (the coating weightening finish is 3% of label weight):
Method for making: got 80 purpose Febuxostats, lactose and sodium carbonate mixing, adding concentration is 2.5% hypromellose aqueous solution, and with mixer mix homogeneously system soft material, 18 mesh sieves are granulated, and in 60 ℃ of dryings, 16 mesh sieve granulate add magnesium stearate, mixing, tabletting.Getting cellulose acetate, PEG400 and diethyl phthalate, is solvent preparation coating solution with 500ml acetone.Above-mentioned label is placed coating in the coating pan, and the coating weightening finish is 3% of label weight, and aging 12h in the rearmounted 40 ℃ of baking ovens of coating promptly gets, and every contains Febuxostat 100mg.Oral 1 of every day.Adopt said method that the release degree of the Febuxostat osmotic pump controlled release tablet of prepared treatment gout is detected, it is (see figure 5) fit zero-order drug release characteristic (correlation coefficient r is 0.992) as a result, and 12h cumulative release percentage rate reaches 92.4%.
Claims (4)
1. Febuxostat osmotic pump controlled release tablet of treating gout, this osmotic pump controlled release tablet comprises label and coating, it is characterized in that; Described label is made up of following components in weight percentage: Febuxostat 10 ~ 40%; Osmotic pressure active substance 30 ~ 60%, alkaline matter 4 ~ 20%, filler 0 ~ 30%; Adhesive 1 ~ 5%, lubricant 0.2 ~ 2%; Described coating is made up of following components in weight percentage: cellulose acetate 40 ~ 70%, PEG400 20 ~ 40%, diethyl phthalate 10 ~ 20%; Wherein,
Described osmotic pressure active substance is one or both the mixture in lactose, glucose, mannitol and the sodium chloride;
Described alkaline matter is sodium carbonate or sodium hydroxide;
Described filler is microcrystalline Cellulose, pre-paying starch or dextrin;
Described adhesive is hypromellose, polyvidone or starch;
Described lubricant is one or both the mixture in magnesium stearate, micropowder silica gel and the Pulvis Talci.
2. according to the said a kind of Febuxostat osmotic pump controlled release tablet of treating gout of claim 1, it is characterized in that described alkaline matter is a sodium carbonate, its content in label is 10 ~ 15%.
3. according to the said a kind of Febuxostat osmotic pump controlled release tablet of treating gout of claim 1, it is characterized in that the content of described PEG400 in coating is 25 ~ 35%.
4. one kind like claim 1,2 or 3 said a kind of method for preparinies of treating the Febuxostat osmotic pump controlled release tablet of gout, and this method is made up of following steps:
With Febuxostat, osmotic pressure active substance, alkaline matter and after filler mixes, add the aqueous solution of adhesive, by hand or mixer mix homogeneously system soft material; 16 or 18 mesh sieves are granulated, and are dry under 60 ℃, 14 or 16 mesh sieve granulate; Add lubricant, mix, be pressed into label with tablet machine; The aqueous solution of wherein said adhesive is to be 10 ~ 50mg/ml aqueous solution with the adhesive concentration that is mixed with soluble in water;
Get cellulose acetate, PEG400 and diethyl phthalate and be dissolved in the acetone, compound concentration is the acetone coating solution of 40 ~ 80mg/ml;
Prepared label is placed coating in the coating pan, and making described label weightening finish is 3 ~ 7%, in 40 ℃ of dryings, the clothing film is solidified behind the coating, promptly gets the Febuxostat osmotic pump controlled release tablet of treating gout.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014194226A3 (en) * | 2013-05-31 | 2015-05-14 | Takeda Pharmaceuticals U.S.A., Inc. | Methods of treatment and compositions with xanthine oxidase inhibitors |
| US20160038595A1 (en) * | 2013-03-15 | 2016-02-11 | Davidoff ALLEN | Xanthine oxidase inhibitor formulations |
| CN115252567A (en) * | 2022-07-08 | 2022-11-01 | 广西纯正堂制药有限公司 | Febuxostat osmotic pump sustained-release tablet and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101259113A (en) * | 2008-04-21 | 2008-09-10 | 沈阳药科大学 | Etodolac osmotic pump type controlled-release preparation and preparation thereof |
| CN102319301A (en) * | 2011-09-27 | 2012-01-18 | 辽宁大学 | Total peony glycoside osmotic pump controlled release tablet and preparation method thereof |
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2012
- 2012-05-08 CN CN2012101406761A patent/CN102641255A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101259113A (en) * | 2008-04-21 | 2008-09-10 | 沈阳药科大学 | Etodolac osmotic pump type controlled-release preparation and preparation thereof |
| CN102319301A (en) * | 2011-09-27 | 2012-01-18 | 辽宁大学 | Total peony glycoside osmotic pump controlled release tablet and preparation method thereof |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20160038595A1 (en) * | 2013-03-15 | 2016-02-11 | Davidoff ALLEN | Xanthine oxidase inhibitor formulations |
| US11406713B2 (en) * | 2013-03-15 | 2022-08-09 | Xortx Therapeutics, Inc. | Xanthine oxidase inhibitor formulations |
| WO2014194226A3 (en) * | 2013-05-31 | 2015-05-14 | Takeda Pharmaceuticals U.S.A., Inc. | Methods of treatment and compositions with xanthine oxidase inhibitors |
| CN115252567A (en) * | 2022-07-08 | 2022-11-01 | 广西纯正堂制药有限公司 | Febuxostat osmotic pump sustained-release tablet and preparation method thereof |
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Application publication date: 20120822 |