CN101953814A - Febuxostat solid preparation - Google Patents
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- CN101953814A CN101953814A CN2009100893693A CN200910089369A CN101953814A CN 101953814 A CN101953814 A CN 101953814A CN 2009100893693 A CN2009100893693 A CN 2009100893693A CN 200910089369 A CN200910089369 A CN 200910089369A CN 101953814 A CN101953814 A CN 101953814A
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Abstract
The invention discloses a febuxostat solid preparation which comprises the components of bulk pharmaceutical chemical febuxostat and pharmaceutic adjuvants which comprises compound efficient disintegrating agent, filler, lubricant and wetting agent. The febuxostat solid preparation is characterized in that the weight ratio of the febuxostat to the compound efficient disintegrating agent is 1:0.1-0.5; and the weight ratio of the febuxostat to the filler is 1: 0.7-1.2. The dissolution rate of the febuxostat solid preparation can achieve over 80% at 45 minutes.
Description
Technical field
The present invention relates to medical technical field, be specifically related to a kind of Febuxostat solid preparation.
Composite highly effective disintegrating agent of the present invention is meant the disintegrating agent compositions of the efficient disintegrating agent composition that adopts two or more.
Efficient disintegrating agent of the present invention includes but not limited to following: hyprolose, polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, microcrystalline Cellulose, chitin or preparation technique development from now on produce new efficient disintegrating agent.
Background technology
Febuxostat, chemical name: 2-[3-cyano group-4-(2-methyl propoxyl group) phenyl]-4-methylthiazol-5-carboxylic acid, the clinical gout that is used for the treatment of.Gout (gout) is because the purine substance metabolism disorder, produce uric acid too much and (or) urate excretion reduces, blood uric acid concentration continues to increase the one group of metabolic disease that causes due to the urate crystal deposition soft tissue.Its clinical manifestation mainly is that the arthritis, gouty nephropathy, gout concretion deposition, the uric acid urinary system concretion that show effect repeatedly generate.It is the biochemical basis of gout that uric acid level raises, and asymptomatic hyperuricemia disease is the state in early stage that gout takes place, and gout must be with hyperuricemia.Say that from classification gout is divided former and secondary two big classes, because enzyme defect caused, most reason was not bright, it and Developmental and Metabolic Disorder syndrome are in close relations but it is now know that, and tangible family heritability is arranged except that minority for originator.Secondary cases patient can be caused by multiple reasons such as nephropathy, hematopathy and medicines.
Along with the prolongation of the change of the improving constantly of people's living standard, dietary structure and living habit, average life, human to the understanding of gout and the raising of diagnostic level, the sickness rate of hyperuricemia and gout is ascendant trend year by year, and age of onset presents and becomes younger.Hyperuricemia and gout are owing to uric acid in the body continues to increase the disease that causes above its physiology permissible range even saturated concentration, so Drug therapy strategy that should disease mainly is exactly to reduce the uric acid that raises in blood and the extracellular fluid.Traditional anti-gout drugs-uricosureic agent (as probenecid, benzbromarone etc.) often is attended by side effect such as erythra, heating, kidney damage.Discover with the xanthine oxidase to be that the inhibitor of action target spot has good gout application prospect, xanthine oxidase inhibitor is as anti-gout drugs, it mainly is the allopurinol of the listing sixties in last century, though be leveraged to the present always, it is only applicable to following 3 kinds of patients: the uricosuric medicine can not make that uric acid concentration in its blood is lower than the patient of 70mg/L, the patient that can not tolerate the uricosuric medicine and cause gout simultaneously with the patient of renal dysfunction because uric acid produces to increase.And a lot of side effect are arranged, using the back patient can have heating, allergic rash, stomachache, diarrhoea, leukocyte and thrombocytopenia, even side effect such as liver function injury is arranged.Therefore, the new xanthine oxidase inhibitor of research has crucial meaning.
Febuxostat is a kind of oral xanthine oxidase inhibitor, is the new drug of first treatment hyperuricemia over 40 years, can reduce the uric acid level in the blood, and stops the crystalline deposition of patient with gout joint uric acid.Its IC
50Value has improved 3 orders of magnitude for 1.4nmol/L than allopurinol.The same with allopurinol, the formation of this product uric acid capable of blocking, and uric acid crystal is deposited on gout patient's joint, causes painful swelling.But allopurinol can suppress the enzyme of a series of participation uric acid paths, and this product then only suppresses xanthine oxidase, thereby its effect has more specificity.Doctor MacDonald of TAP company thinks that this difference between the effects makes that in theory Febuxostat is more safer than allopurinol.Allopurinol can cause about 1%～2% patient and side effect occur, and wherein 25% or even fatal.Febuxostat may more be applicable to the renal failure patient, and allopurinol is via renal excretion mainly at liver metabolism.The III clinical trial phase data show of in October, 2004 U.S.'s rheumatology association issue, the curative effect of Febuxostat is better than the golden standard curative allopurinol of present gout.
The Febuxostat tablet is successfully listing abroad, consults domestic and foreign literature, discloses its preparation prescription abroad, has only raw material and pharmaceutic adjuvant in the prescription, and without any the information about recipe quantity; Chinese patent 200610095263.0 discloses the solid preparation of the Febuxostat of different crystal forms, there is not quality standard according to solid preparation, dissolution index particularly, carry out prescription screening, and be that a kind of disintegrating agent of use or a kind of efficient disintegrating agent of " assuming as a matter of course " carries out the preparation of solid preparation, such solid preparation quality can't be qualified.
Summary of the invention
For these reasons, the scientific research personnel of the court is by secular creationary research, according to Febuxostat physics and chemical property, discovery is in preparation Febuxostat solid preparation, Febuxostat concerns with the weight ratio that composite highly effective disintegrating agent, filler have respectively, solid preparation according to the preparation of above-mentioned weight ratio relation has good dissolution, illustrates that Febuxostat solid preparation product quality of the present invention is very outstanding.
Composite highly effective disintegrating agent of the present invention is meant the disintegrating agent compositions of the efficient disintegrating agent composition that adopts two or more.
Lubricant of the present invention and wetting agent are an amount of in formulation preparation, and selected kind includes but not limited to conventional lubricant and the wetting agent that uses of solid preparation
The present invention is achieved through the following technical solutions.
A kind of Febuxostat solid preparation, be prepared from by crude drug Febuxostat and pharmaceutic adjuvant, pharmaceutic adjuvant is composite highly effective disintegrating agent, filler, lubricant and wetting agent, the weight ratio 1 that it is characterized in that Febuxostat and composite highly effective disintegrating agent: 0.1-0.5, the weight ratio of Febuxostat and filler is 1: 0.7-1.2.
The condition that solid preparation of the present invention conforms to quality requirements is to satisfy above-mentioned described disintegrating agent, filler and raw material weight ratio simultaneously.
The weight of above-mentioned described lubricant and wetting agent is an amount of, and kind is to include but not limited to conventional lubricant and the wetting agent that uses of solid preparation.
Wherein the weight ratio of Febuxostat and composite highly effective disintegrating agent is 1: 0.3338, and the weight ratio of Febuxostat and filler is 1: 0.8825.
The condition that solid preparation of the present invention conforms to quality requirements is to satisfy above-mentioned described efficient disintegrating agent, filler and raw material weight ratio simultaneously.
The weight of above-mentioned described lubricant and wetting agent is an amount of, and kind is to include but not limited to conventional lubricant and the wetting agent that uses of solid preparation.
Wherein the weight ratio of Febuxostat and composite highly effective disintegrating agent is 1: 0.1125, and the weight ratio of Febuxostat and filler is 1: 1.1038.
The condition that solid preparation of the present invention conforms to quality requirements is to satisfy above-mentioned described disintegrating agent, filler and raw material weight ratio simultaneously.
The weight of above-mentioned described lubricant and wetting agent is an amount of, and kind is to include but not limited to conventional lubricant and the wetting agent that uses of solid preparation.
Wherein solid preparation is capsule, tablet, granule or pellet.
Wherein the pharmaceutic adjuvant filler is one or more in lactose, starch, dextrin, Icing Sugar, microcrystalline Cellulose, pregelatinized Starch, mannitol, calcium hydrogen phosphate, the calcium sulfate.
Wherein pharmaceutic adjuvant composite highly effective disintegrating agent is several in hyprolose, polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, microcrystalline Cellulose, the chitin.
Wherein the pharmaceutic adjuvant lubricant is one or more in fatty acid magnesium, Pulvis Talci, micropowder silica gel, the Polyethylene Glycol.
One, determination of dissolution rate
1, dissolution determination method
According to dissolution method (2005 editions two appendix XC second methods of Chinese Pharmacopoeia), with pH6.8 phosphate buffer 1 000ml is dissolution medium, rotating speed is that per minute 75 changes, operation in the time of 45 minutes, is got solution 5ml in accordance with the law, filter, get subsequent filtrate 1ml and put in the 10ml measuring bottle, and be diluted to scale, measure absorbance at the 315nm place according to ultraviolet visible spectrophotometry (2005 editions two appendix IV A of Chinese Pharmacopoeia) with dissolution medium; Other gets the about 8mg of Febuxostat reference substance, and accurate the title decides, and puts in the 100ml measuring bottle, it is an amount of to add dissolution medium, made dissolving in ultrasonic 5 minutes, and added the stripping medium, shake up to scale, precision is measured 1ml, put in the 10ml measuring bottle, add the stripping medium, shake up to scale, measure with method, calculate every stripping quantity.
2, the dissolution of different preparations relatively
Scheme 1: Febuxostat solid preparation of the present invention.
Scheme 2: the Febuxostat sheet abroad goes on the market.
Scheme 3: the capsule of Chinese patent 200610095263.0 embodiment 5.
Scheme 4: the tablet of Chinese patent 200610095263.0 embodiment 6.
Scheme 5: the tablet of Chinese patent 200610095263.0 embodiment 7.
Experimental technique: detect according to above-mentioned dissolution determination method, experimental result sees Table 1.
The dissolution of the different preparations of table 1
Experiment conclusion: above-mentioned dissolution check and analysis result shows, the preparation dissolution of preparation prescription preparation of the present invention can reach more than 90%, and the dissolution of the solid preparation of disclosed Chinese patent is all undesirable, the research that said preparation is described is not carried out deep research according to the character of Febuxostat, particularly to the research of dissolution, just studied the molding of preparation, to the not research of quality of preparation.
Two, prescription screening and technical study process
1, prescription screening one
| Febuxostat | 8.00g |
| The composite highly effective disintegrating agent | 0.70g |
| Filler | 4.80g |
| Lubricant | In right amount |
| Wetting agent | In right amount |
| Make altogether | 100 |
Annotate: dissolution determination method is according to the above-mentioned described dissolution determination method of the present invention
Preparation technology: standby after principal agent, composite highly effective disintegrating agent, filler, lubricant sieve respectively; Composite highly effective disintegrating agent, filler mix homogeneously with mix homogeneously, add principal agent and the adjuvant that mixed wetting agent with the above-mentioned adjuvant that has mixed again and make soft material in right amount, granulation, drying, granulate; Add lubricant, mix homogeneously.According to the conventional preparation method preparation of solid preparation.
Experimental result: the result sees Table 2.
Table 2 Febuxostat tablet recipe one index of correlation is investigated the result
| The investigation project | Prescription 1 |
| Mobility of particle (angle of repose ℃) | 29.7 |
| Particle drying weightlessness (%) | 4.6 |
| Outward appearance | Unilateral bright and clean |
| Hardness (N) | 45N |
| Disintegration (branch) | 9 minutes |
| Dissolution (%) | 61.2 |
Discuss: above-mentioned prescription mobility of particle is better, made sample strip appearance looks elegant.But it is undesirable according to the made sample strip dissolution of prescription.This prescription composite highly effective disintegrant content is low excessively, and filler content is low excessively, and the tablet compressibility is bad, considers to increase the consumption of composite highly effective disintegrating agent, increases the consumption of filler.According to above analysis, two the research of having carried out writing out a prescription.
2, prescription screening two
| Febuxostat | 8.00g |
| The composite highly effective disintegrating agent | 0.80g |
| Filler | 5.60g |
| Lubricant | In right amount |
| Wetting agent | In right amount |
| Make altogether | 100 |
Preparation technology: preparation technology is with prescription one
Experimental result: the result sees Table 3.
Table 3 Febuxostat tablet recipe two relevant indexs are investigated the result
| The investigation project | Prescription 2 |
| Mobility of particle (angle of repose) | 29.5 |
| Particle drying weightlessness (%) | 3.9 |
| Outward appearance | Unilateral bright and clean |
| Hardness (N) | 38N |
| Disintegration (branch) | 5 |
| Dissolution (%) | 80.3 |
Discuss: above-mentioned prescription mobility of particle is better, made sample strip appearance looks elegant.Because changed the usage ratio of composite highly effective disintegrating agent, filler, the tablet compressibility makes moderate progress, hardness descends to some extent, the result of extraction composite demand.In order to obtain the product of better quality, three the research of having carried out writing out a prescription.
3, prescription screening three
| Febuxostat | 8.00g |
| The composite highly effective disintegrating agent | 2.67g |
| Filler | 7.06g |
| Lubricant | In right amount |
| Wetting agent | In right amount |
| Make altogether | 100 |
Preparation technology: preparation technology is with prescription one.
Experimental result: the results are shown in Table 4.
Table 4 Febuxostat tablet recipe three relevant indexs are investigated the result
| The investigation project | Prescription 3 |
| Mobility of particle (angle of repose) | 28.3 |
| Particle drying weightlessness (%) | 3.8 |
| Outward appearance | Unilateral bright and clean, attractive in appearance |
| Hardness (N) | 37N |
| Disintegration (branch) | In 3 minutes |
| Dissolution (%) | 95.6 |
Discuss: above-mentioned prescription mobility of particle is better, made sample strip appearance looks elegant; The every index of preparation all meets the requirements, and belongs to the outstanding preparation of quality, and we continue research.
4, prescription four
| Febuxostat | 8.00g |
| The composite highly effective disintegrating agent | 0.90g |
| Filler | 8.83g |
| Lubricant | In right amount |
| Wetting agent | In right amount |
| Make altogether | 100 |
Preparation technology: preparation technology is with prescription one.
Experimental result: the results are shown in Table 5.
Table 5 Febuxostat tablet recipe four indexs of correlation are investigated the result
| The investigation project | Prescription 4 |
| Mobility of particle (angle of repose) | 29.6 |
| Particle drying weightlessness (%) | 4.0 |
| Outward appearance | Unilateral bright and clean, attractive in appearance |
| Hardness (N) | 39N |
| Disintegration (branch) | In 3 minutes |
| Dissolution (%) | 95.9 |
Discuss: above-mentioned prescription mobility of particle is better, made sample strip appearance looks elegant; The every index of preparation all meets the requirements, and belongs to the preparation of outstanding product quality, and we continue research.
5, prescription five
| Febuxostat | 8.00g |
| The composite highly effective disintegrating agent | 4.00g |
| Filler | 9.6g |
| Lubricant | In right amount |
| Wetting agent | In right amount |
| Make altogether | 100 |
Preparation technology: preparation technology is with prescription one.
Experimental result: the results are shown in Table 6.
Table 6 Febuxostat tablet recipe four indexs of correlation are investigated the result
| The investigation project | Prescription 4 |
| Mobility of particle (angle of repose) | 31.57 |
| Particle drying weightlessness (%) | 3.9 |
| Outward appearance | Unilateral bright and clean, attractive in appearance |
| Hardness (N) | 42N |
| Disintegration (branch) | In 5 minutes |
| Dissolution (%) | 81-3 |
Discuss: above-mentioned prescription mobility of particle is better, made sample strip appearance looks elegant; The every index of preparation all meets the requirements, but the decline of dissolution index, we further study.
6, prescription six
| Febuxostat | 8.00g |
| The composite highly effective disintegrating agent | 4.8g |
| Filler | 10.4g |
| Lubricant | In right amount |
| Wetting agent | In right amount |
| Make altogether | 100 |
Preparation technology: preparation technology is with prescription one.
Experimental result: the results are shown in Table 7.
Table 7 Febuxostat tablet recipe four indexs of correlation are investigated the result
| The investigation project | Prescription 4 |
| Mobility of particle (angle of repose) | 26.91 |
| Particle drying weightlessness (%) | 4.1 |
| Outward appearance | Unilateral bright and clean |
| Hardness (N) | 40N |
| Disintegration (branch) | In 9 minutes |
| Dissolution (%) | 68.94 |
Discuss: above-mentioned prescription mobility of particle is bad, and the every index of made sample formulation is all undesirable.
Annotate: above-mentioned experiment is the representativeness experiment in repeatedly testing.
Annotate: according to above-mentioned experimental technique, screen the prescription of other solid preparations, experimental result is close with above-mentioned experimental result.
Conclusion: by above-mentioned experiment, we obtain:
A kind of Febuxostat solid preparation, it consists of crude drug Febuxostat and pharmaceutic adjuvant, pharmaceutic adjuvant is composite highly effective disintegrating agent, filler, lubricant and wetting agent, the weight ratio 1 that it is characterized in that Febuxostat and composite highly effective disintegrating agent: 0.1-0.5, the weight ratio of Febuxostat and filler is 1: 0.7-1.2.The condition that described solid preparation conforms to quality requirements is to satisfy above-mentioned described disintegrating agent, filler and raw material weight ratio simultaneously.The weight of above-mentioned described lubricant and wetting agent is an amount of, and kind is to include but not limited to conventional lubricant and the wetting agent that uses of solid preparation.
Wherein the weight ratio of Febuxostat and composite highly effective disintegrating agent is 1: 0.3338, and the weight ratio of Febuxostat and filler is 1: 0.8825.The condition that described solid preparation conforms to quality requirements is to satisfy above-mentioned described disintegrating agent, filler and raw material weight ratio simultaneously.The weight of above-mentioned described lubricant and wetting agent is an amount of, and kind is to include but not limited to conventional lubricant and the wetting agent that uses of solid preparation.
Wherein the weight ratio of Febuxostat and composite highly effective disintegrating agent is 1: 0.1125, and the weight ratio of Febuxostat and filler is 1: 1.1038.The condition that described solid preparation conforms to quality requirements is to satisfy above-mentioned described disintegrating agent, filler and raw material weight ratio simultaneously.The weight of described lubricant and wetting agent is an amount of, and kind is to include but not limited to conventional lubricant and the wetting agent that uses of solid preparation.
Three, preparation embodiment
Embodiment 1
Febuxostat 80g, composite highly effective disintegrating agent 8g, filler 56g, wetting agent is an amount of, and lubricant is an amount of.
Prepare according to the solid preparation conventional method.
Wherein solid preparation is capsule, tablet, granule or pellet.
The composite highly effective disintegrating agent of above-mentioned described pharmaceutic adjuvant includes but not limited to preparation solid preparation composite highly effective disintegrating agent commonly used in the pharmaceutics.Include but not limited to that chitin, hyprolose, polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, microcrystalline Cellulose are several.
The filler of above-mentioned described pharmaceutic adjuvant includes but not limited to preparation solid preparation filler commonly used in the pharmaceutics.Include but not limited in lactose, starch, dextrin, Icing Sugar, microcrystalline Cellulose, pregelatinized Starch, mannitol, calcium hydrogen phosphate, the calcium sulfate one or more.
The lubricant of above-mentioned described pharmaceutic adjuvant includes but not limited to preparation solid preparation lubricant commonly used in the pharmaceutics.Include but not limited in magnesium stearate, Pulvis Talci, micropowder silica gel, the Polyethylene Glycol one or more.
Embodiment 2
Febuxostat 80g, composite highly effective disintegrating agent 40g, filler 96g, wetting agent is an amount of, and lubricant is an amount of.
Prepare according to the solid preparation conventional method.
Wherein solid preparation is capsule, tablet, granule or pellet.
The composite highly effective disintegrating agent of above-mentioned described pharmaceutic adjuvant includes but not limited to preparation solid preparation composite highly effective disintegrating agent commonly used in the pharmaceutics.Include but not limited to that chitin, hyprolose, polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, microcrystalline Cellulose are several.
The filler of above-mentioned described pharmaceutic adjuvant includes but not limited to preparation solid preparation filler commonly used in the pharmaceutics.Include but not limited in lactose, starch, dextrin, Icing Sugar, microcrystalline Cellulose, pregelatinized Starch, mannitol, calcium hydrogen phosphate, the calcium sulfate one or more.
The lubricant of above-mentioned described pharmaceutic adjuvant includes but not limited to preparation solid preparation lubricant commonly used in the pharmaceutics.Include but not limited in magnesium stearate, Pulvis Talci, micropowder silica gel, the Polyethylene Glycol one or more.
Embodiment 3
Febuxostat 80g, composite highly effective disintegrating agent 16g, filler 64g, wetting agent is an amount of, and lubricant is an amount of.
Prepare according to the solid preparation conventional method.
Wherein solid preparation is capsule, tablet, granule or pellet.
The composite highly effective disintegrating agent of above-mentioned described pharmaceutic adjuvant includes but not limited to preparation solid preparation composite highly effective disintegrating agent commonly used in the pharmaceutics.Include but not limited to that chitin, hyprolose, polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, microcrystalline Cellulose are several.
The filler of above-mentioned described pharmaceutic adjuvant includes but not limited to preparation solid preparation filler commonly used in the pharmaceutics.Include but not limited in lactose, starch, dextrin, Icing Sugar, microcrystalline Cellulose, pregelatinized Starch, mannitol, calcium hydrogen phosphate, the calcium sulfate one or more.
The lubricant of above-mentioned described pharmaceutic adjuvant includes but not limited to preparation solid preparation lubricant commonly used in the pharmaceutics.Include but not limited in magnesium stearate, Pulvis Talci, micropowder silica gel, the Polyethylene Glycol one or more.
Embodiment 4
Febuxostat 80g, composite highly effective disintegrating agent 24g, filler 72g, wetting agent is an amount of, and lubricant is an amount of.
Prepare according to the solid preparation conventional method.
Wherein solid preparation is capsule, tablet, granule or pellet.
The composite highly effective disintegrating agent of above-mentioned described pharmaceutic adjuvant includes but not limited to preparation solid preparation composite highly effective disintegrating agent commonly used in the pharmaceutics.Include but not limited to that chitin, hyprolose, polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, microcrystalline Cellulose are several.
The filler of above-mentioned described pharmaceutic adjuvant includes but not limited to preparation solid preparation filler commonly used in the pharmaceutics.Include but not limited in lactose, starch, dextrin, Icing Sugar, microcrystalline Cellulose, pregelatinized Starch, mannitol, calcium hydrogen phosphate, the calcium sulfate one or more.
The lubricant of above-mentioned described pharmaceutic adjuvant includes but not limited to preparation solid preparation lubricant commonly used in the pharmaceutics.Include but not limited in magnesium stearate, Pulvis Talci, micropowder silica gel, the Polyethylene Glycol one or more.
Embodiment 5
Febuxostat 80g, composite highly effective disintegrating agent 32g, filler 81g, wetting agent is an amount of, and lubricant is an amount of.
Prepare according to the solid preparation conventional method.
Wherein solid preparation is capsule, tablet, granule or pellet.
The composite highly effective disintegrating agent of above-mentioned described pharmaceutic adjuvant includes but not limited to preparation solid preparation composite highly effective disintegrating agent commonly used in the pharmaceutics.Include but not limited to that chitin, hyprolose, polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, microcrystalline Cellulose are several.
The filler of above-mentioned described pharmaceutic adjuvant includes but not limited to preparation solid preparation filler commonly used in the pharmaceutics.Include but not limited in lactose, starch, dextrin, Icing Sugar, microcrystalline Cellulose, pregelatinized Starch, mannitol, calcium hydrogen phosphate, the calcium sulfate one or more.
The lubricant of above-mentioned described pharmaceutic adjuvant includes but not limited to preparation solid preparation lubricant commonly used in the pharmaceutics.Include but not limited in magnesium stearate, Pulvis Talci, micropowder silica gel, the Polyethylene Glycol one or more.
Embodiment 6
Febuxostat 80g, composite highly effective disintegrating agent 32g, filler 80g, wetting agent is an amount of, and lubricant is an amount of.
Prepare according to the solid preparation conventional method.
Wherein solid preparation is capsule, tablet, granule or pellet.
The composite highly effective disintegrating agent of above-mentioned described pharmaceutic adjuvant includes but not limited to preparation solid preparation composite highly effective disintegrating agent commonly used in the pharmaceutics.Include but not limited to that chitin, hyprolose, polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, microcrystalline Cellulose are several.
The filler of above-mentioned described pharmaceutic adjuvant includes but not limited to preparation solid preparation filler commonly used in the pharmaceutics.Include but not limited in lactose, starch, dextrin, Icing Sugar, microcrystalline Cellulose, pregelatinized Starch, mannitol, calcium hydrogen phosphate, the calcium sulfate one or more.
The lubricant of above-mentioned described pharmaceutic adjuvant includes but not limited to preparation solid preparation lubricant commonly used in the pharmaceutics.Include but not limited in magnesium stearate, Pulvis Talci, micropowder silica gel, the Polyethylene Glycol one or more.
Embodiment 7
Febuxostat 80g, composite highly effective disintegrating agent 26.7g, filler 70.6g, wetting agent is an amount of, and lubricant is an amount of.
Prepare according to the solid preparation conventional method.
Wherein solid preparation is capsule, tablet, granule or pellet.
The composite highly effective disintegrating agent of above-mentioned described pharmaceutic adjuvant includes but not limited to preparation solid preparation composite highly effective disintegrating agent commonly used in the pharmaceutics.Include but not limited to that chitin, hyprolose, polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, microcrystalline Cellulose are several.
The filler of above-mentioned described pharmaceutic adjuvant includes but not limited to preparation solid preparation filler commonly used in the pharmaceutics.Include but not limited in lactose, starch, dextrin, Icing Sugar, microcrystalline Cellulose, pregelatinized Starch, mannitol, calcium hydrogen phosphate, the calcium sulfate one or more.
The lubricant of above-mentioned described pharmaceutic adjuvant includes but not limited to preparation solid preparation lubricant commonly used in the pharmaceutics.Include but not limited in magnesium stearate, Pulvis Talci, micropowder silica gel, the Polyethylene Glycol one or more.
Embodiment 8
Febuxostat 80g, composite highly effective disintegrating agent 9g, filler 88.3g, wetting agent is an amount of, and lubricant is an amount of.
Prepare according to the solid preparation conventional method.
Wherein solid preparation is capsule, tablet, granule or pellet.
The composite highly effective disintegrating agent of above-mentioned described pharmaceutic adjuvant includes but not limited to preparation solid preparation composite highly effective disintegrating agent commonly used in the pharmaceutics.Include but not limited to that chitin, hyprolose, polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, microcrystalline Cellulose are several.
The filler of above-mentioned described pharmaceutic adjuvant includes but not limited to preparation solid preparation filler commonly used in the pharmaceutics.Include but not limited in lactose, starch, dextrin, Icing Sugar, microcrystalline Cellulose, pregelatinized Starch, mannitol, calcium hydrogen phosphate, the calcium sulfate one or more.
The lubricant of above-mentioned described pharmaceutic adjuvant includes but not limited to preparation solid preparation lubricant commonly used in the pharmaceutics.Include but not limited in magnesium stearate, Pulvis Talci, micropowder silica gel, the Polyethylene Glycol one or more.
Embodiment 9
Febuxostat 80g, composite highly effective disintegrating agent 32g, filler 88g, wetting agent is an amount of, and lubricant is an amount of.
Prepare according to the solid preparation conventional method.
Wherein solid preparation is capsule, tablet, granule or pellet.
The composite highly effective disintegrating agent of above-mentioned described pharmaceutic adjuvant includes but not limited to preparation solid preparation composite highly effective disintegrating agent commonly used in the pharmaceutics.Include but not limited to that chitin, hyprolose, polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, microcrystalline Cellulose are several.
The filler of above-mentioned described pharmaceutic adjuvant includes but not limited to preparation solid preparation filler commonly used in the pharmaceutics.Include but not limited in lactose, starch, dextrin, Icing Sugar, microcrystalline Cellulose, pregelatinized Starch, mannitol, calcium hydrogen phosphate, the calcium sulfate one or more.
The lubricant of above-mentioned described pharmaceutic adjuvant includes but not limited to preparation solid preparation lubricant commonly used in the pharmaceutics.Include but not limited in magnesium stearate, Pulvis Talci, micropowder silica gel, the Polyethylene Glycol one or more.
Annotate: the present invention's concrete technical scheme required for protection is not limited to the concrete combination of the expressed technical scheme of the foregoing description.
Those skilled in the art can carry out various variations and change to the preferred version that the present application is described, and this variation and change can be carried out under the situation of its advantage not deviating from essence of the present invention and scope and do not reduce; Therefore, the present patent application claim covers above-mentioned this variation and change, includes but not limited to equivalent way.
Claims (7)
1. Febuxostat solid preparation, be prepared from by crude drug Febuxostat and pharmaceutic adjuvant, pharmaceutic adjuvant is composite highly effective disintegrating agent, filler, lubricant and wetting agent, the weight ratio 1 that it is characterized in that Febuxostat and composite highly effective disintegrating agent: 0.1-0.5, the weight ratio of Febuxostat and filler is 1: 0.7-1.2.
2. a kind of Febuxostat solid preparation according to claim 1, wherein the weight ratio of Febuxostat and composite highly effective disintegrating agent is 1: 0.3338, the weight ratio of Febuxostat and filler is 1: 0.8825.
3. a kind of Febuxostat solid preparation according to claim 1, wherein the weight ratio of Febuxostat and composite highly effective disintegrating agent is 1: 0.1125, the weight ratio of Febuxostat and filler is 1: 1.1038.
4. according to claim 1,2,3 each described a kind of Febuxostat solid preparations, wherein solid preparation is capsule, tablet, granule or pellet.
5. according to each described a kind of Febuxostat solid preparation of claim 1-3, wherein the pharmaceutic adjuvant filler is one or more in lactose, starch, dextrin, Icing Sugar, microcrystalline Cellulose, pregelatinized Starch, mannitol, calcium hydrogen phosphate, the calcium sulfate.
6. according to each described a kind of Febuxostat solid preparation of claim 1-3, wherein pharmaceutic adjuvant composite highly effective disintegrating agent is several in hyprolose, polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, microcrystalline Cellulose, the chitin.
7. according to each described a kind of Febuxostat solid preparation of claim 1-3, wherein the pharmaceutic adjuvant lubricant is one or more in fatty acid magnesium, Pulvis Talci, micropowder silica gel, the Polyethylene Glycol.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101940562A (en) * | 2010-08-25 | 2011-01-12 | 石药集团欧意药业有限公司 | Solid preparation of febuxostat or medicinal salt thereof and preparation method thereof |
| CN102488665A (en) * | 2011-12-15 | 2012-06-13 | 宁夏康亚药业有限公司 | Febuxostat tablet and preparation method thereof |
| CN102614145A (en) * | 2012-04-28 | 2012-08-01 | 杭州朱养心药业有限公司 | Stable febuxostat tablet and preparation method thereof |
| CN102614146A (en) * | 2012-04-28 | 2012-08-01 | 杭州朱养心药业有限公司 | Method for preparing febuxostat tablet and febuxostat tablet |
| WO2012153313A1 (en) | 2011-05-11 | 2012-11-15 | Ranbaxy Laboratories Limited | Pharmaceutical composition of febuxostat |
| CN102895209A (en) * | 2011-12-15 | 2013-01-30 | 宁夏康亚药业有限公司 | Febuxostat tablet |
| CN102895210A (en) * | 2011-12-15 | 2013-01-30 | 宁夏康亚药业有限公司 | Febuxostat tablet with improved dissolution rate |
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| CN1954814A (en) * | 2005-10-26 | 2007-05-02 | 重庆医药工业研究院有限责任公司 | Medical composite with co-action for treating gout and its preparation method |
| CN101474175A (en) * | 2009-01-20 | 2009-07-08 | 重庆医药工业研究院有限责任公司 | Oral solid preparation of Febuxostat with high-bioavailability and preparation method thereof |
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| CN1954814A (en) * | 2005-10-26 | 2007-05-02 | 重庆医药工业研究院有限责任公司 | Medical composite with co-action for treating gout and its preparation method |
| CN101474175A (en) * | 2009-01-20 | 2009-07-08 | 重庆医药工业研究院有限责任公司 | Oral solid preparation of Febuxostat with high-bioavailability and preparation method thereof |
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101940562A (en) * | 2010-08-25 | 2011-01-12 | 石药集团欧意药业有限公司 | Solid preparation of febuxostat or medicinal salt thereof and preparation method thereof |
| CN101940562B (en) * | 2010-08-25 | 2012-08-22 | 石药集团欧意药业有限公司 | Solid preparation of febuxostat or medicinal salt thereof and preparation method thereof |
| WO2012153313A1 (en) | 2011-05-11 | 2012-11-15 | Ranbaxy Laboratories Limited | Pharmaceutical composition of febuxostat |
| CN102488665A (en) * | 2011-12-15 | 2012-06-13 | 宁夏康亚药业有限公司 | Febuxostat tablet and preparation method thereof |
| CN102895209A (en) * | 2011-12-15 | 2013-01-30 | 宁夏康亚药业有限公司 | Febuxostat tablet |
| CN102895210A (en) * | 2011-12-15 | 2013-01-30 | 宁夏康亚药业有限公司 | Febuxostat tablet with improved dissolution rate |
| CN102895209B (en) * | 2011-12-15 | 2013-12-25 | 宁夏康亚药业有限公司 | Febuxostat tablet |
| CN102895210B (en) * | 2011-12-15 | 2014-08-06 | 宁夏康亚药业有限公司 | Febuxostat tablet with improved dissolution rate |
| CN102614145A (en) * | 2012-04-28 | 2012-08-01 | 杭州朱养心药业有限公司 | Stable febuxostat tablet and preparation method thereof |
| CN102614146A (en) * | 2012-04-28 | 2012-08-01 | 杭州朱养心药业有限公司 | Method for preparing febuxostat tablet and febuxostat tablet |
| CN102614145B (en) * | 2012-04-28 | 2013-05-01 | 杭州朱养心药业有限公司 | Stable febuxostat tablet and preparation method thereof |
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