CN101836959A - Method for preparing almost bitterless rifaximin dry suspension - Google Patents
Method for preparing almost bitterless rifaximin dry suspension Download PDFInfo
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- CN101836959A CN101836959A CN201010177930A CN201010177930A CN101836959A CN 101836959 A CN101836959 A CN 101836959A CN 201010177930 A CN201010177930 A CN 201010177930A CN 201010177930 A CN201010177930 A CN 201010177930A CN 101836959 A CN101836959 A CN 101836959A
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Abstract
The invention provides a method for preparing an almost bitterless rifaximin dry suspension. The method comprises the following steps of: passing rifaximin through 20-35 percent ethanol solution; then drying the rifaximin under the condition that the temperature is no more than 60 DEG C; sieving the dried rifaximin to a certain particle size; and mixing the rifaximin with a filling agent namely lactose, a suspending agent namely hydroxypropyl methyl cellulose, a flavoring agent namely aspartame and an essence to prepare the rifaximin dry suspension.
Description
Technical field
The present invention relates to a kind of preparation does not almost have the method for bitterness Rifaximin dry suspension agent, belongs to the technical field of pharmaceutical preparation.
Background technology
Rifaximin is a wide spectrum intestinal antibiotic.It is the semi-synthetic derivant of Rifamycin Sodium.Develop by Italian Alfa Wassermann.Rifaximin is the same with other rifamycinoid antibioticses, by suppressing the synthetic of bacteria RNA with irreversible combination of the beta subunit of DNA of bacteria-dependenc RNA polymerase, finally suppresses the synthetic of bacterioprotein.Because it is irreversible with combining of enzyme, so its activity is the bactericidal activity to sensitive organism.To studies show that of rifaximin antibacterial activity, this product and rifamycin have antimicrobial spectrum equally widely, to most gram positive bacterias and gram negative bacteria, comprise that the infection of aerobe and anaerobe has bactericidal action.
Different with the anti-infectives that other whole body absorbs, not by intestinal absorption, wait other systemic reactions after rifaximin is oral thereby reduced to interact between the generation of antibiotic resistance and the medicine.So this product can be used as specific intestinal tract disease curative.Rifaximin is used for acute and chronic intestinal infection, diarrhoea, enterocolitis etc. clinically, and as the auxiliary therapeutic agent and the perioperative intestinal prophylactic of hyperammonemia, is effective and safe drug.
Rifaximin is water-soluble hardly, and dry suspension is the preferred peroral dosage form of rifaximin, is suitable for the child and the old man takes.
Rifaximin is the very bitter medicine of a kind of taste, by conventional method, such as with medicine and filler, flavoring agents etc. mix or with medicine and filler, flavoring agent mixes the Rifaximin dry suspension agent of method preparations such as back granulation, takes after the bath, taste is very bitter, and the child can't accept and refuse to take.For this reason, rifaximin is developed to dry suspension, the bitterness problem when solving it and taking is the problem that at first will solve.So there is demand in the Rifaximin dry suspension agent that has a good taste for preparation in the art.
The present invention explores by test, and accident has obtained the method that a kind of preparation does not almost have the Rifaximin dry suspension agent of bitterness, and the important point is that this method technology is simple in addition, and cost is low, is easy to produce amplify.
Summary of the invention
Rifaximin dry suspension agent does not have the preparation of bitterness substantially because the intensive bitterness of rifaximin is difficult to obtain good mouthfeel by the general preparation method of dry suspension.The inventor is by the bitterness of the whole bag of tricks try to cover up rifaximin.By adding high-molecular weight blocker; as hypromellose; sodium carboxymethyl cellulose; polyvidone, methylcellulose, xanthan gum, arabic gum, sodium alginate, carbomer etc.; purpose for stop or delay the bath after; the rifaximin of minimal amounts of dissolved spreads to taste bud, and polymer binder has packaging medicine and forms the protecting film effect at taste bud in addition, and reaches the purpose that reduces bitterness.Alleviated the bitterness of Rifaximin dry suspension agent to a certain extent by this method, but effect is limited, still can feels obviously bitterness after taking.
Research worker is passed through rifaximin and stomach dissolution type mixed with resin, the dissolving parcel, purpose is to have the rifaximin raw material of bitterness to wrap up in advance, bitterness when elimination is taken, owing to be the stomach dissolution type resin, discharge rifaximin in the dissolving of stomach acid ph value, and can not dissolve in the nearly neutral pH value environment in the oral cavity when taking, and reach the purpose of covering the rifaximin bitterness.If this method parcel fully, can reach the purpose of covering bitterness fully.But test shows that the required organic solvent amount of this method is bigger, could realize better wrapping up effect.In addition, this technology is in amplifying production operation, and technology is complicated, is difficult for industrialization.
Research worker is by adding relatively large sweeting agent and essence in the dry suspension prescription, such as rifaximin and sweeting agent are fully mixed, and be mixed with dry suspension with other adjuvant or by the preparation dry suspension of granulating, this method is simple to operation, but mouthfeel is undesirable, has the phenomenon of tangible bitterness and sweet taste coexistence.
In addition, the powder coating method if coating effect is good, can be covered bitterness fully, but also there is certain technical difficulty in this method at present in big production, and production cost is higher.
Method of the present invention is unexpected discovery the in the research worker process of the test, research worker is found to wash the rifaximin raw material in advance when the alcoholic solution with an amount of concentration, after the drying, bitterness reduces greatly, again with other flavoring agent, the Rifaximin dry suspension agent that is mixed with as sucrose, aspartame etc. does not have bitterness substantially, good mouthfeel.The concentration of described alcoholic solution is preferably 20～35%, and more preferably 25%～30%, most preferably be 28%.Baking temperature is no more than 60 ℃.
The inventor is by studying the structure of the rifaximin after the above-mentioned washing, and the result shows, compares with the rifaximin that washs preceding bitter in the mouth, and structure does not change.The material base that shows Drug therapy does not change.
The inventor also studies the crystal formation of the rifaximin after the above-mentioned washing, and the result shows, compares with the rifaximin that washs preceding bitter in the mouth, and variation has taken place crystal formation, and the reason that bitterness disappears substantially may change relevant with its crystal formation.The change of crystal formation may influence the dissolubility of medicine, thereby influences the dissolution in vitro of medicine.Given this, research worker does not almost have the quality of two kinds of Rifaximin dry suspension agents of bitterness after to bitter in the mouth before washing and washing and has carried out comparative study, comprises two important indicator dissolution and the related substances relevant with medication effect and untoward reaction.Result of study shows dissolution and the equal no significant difference of related substance.
In addition, the inventor is also by using other media, ethyl acetate for example, and acetone, methanol etc. are by the rifaximin of above-mentioned same procedure washing bitter in the mouth, but DeGrain.
The present invention provides following embodiment at least:
1, a kind of preparation does not almost have the method for bitterness Rifaximin dry suspension agent, and rifaximin by 20～35% (V/V) ethanol water, is washed.
2, the method for embodiment 1 after the washing, be not higher than drying under 60 ℃ of conditions.
5, the method for embodiment 2 further comprises dried rifaximin is sieved to certain particle size, and with filler sucrose, suspending agent hydroxypropyl emthylcellulose, flavoring agent aspartame and essence mix, the preparation Rifaximin dry suspension agent.
The specific embodiment
Embodiment
Further specify the present invention below by embodiment, be convenient to better understand the present invention.Yet scope of the present invention is not limited to these embodiment.Unless stated otherwise, all commercially available acquisition of all reagent.
The preparation Rifaximin dry suspension agent, to its mouthfeel, several personnel taste, and grading system is as follows: A, mouthfeel is good, does not have bitterness substantially; B, mouthfeel is general, and certain bitterness is arranged; C, mouthfeel is bad, bitter in the mouth.
Embodiment 1:
Rifaximin is washed with 28% alcoholic solution, stir 3 minutes after-filtration, dry under 40 ℃ of conditions, pulverized 40 mesh sieves, mix promptly with sucrose, hypromellose, aspartame, essence.Grading system: A.
Embodiment 2:
Rifaximin is washed with 15% alcoholic solution, stir 3 minutes after-filtration, dry under 40 ℃ of conditions, pulverized 40 mesh sieves, mix promptly with sucrose, hypromellose, aspartame, essence.Grading system: B.
Embodiment 3:
Rifaximin is washed with 40% alcoholic solution, stir 3 minutes after-filtration, dry under 40 ℃ of conditions, pulverized 40 mesh sieves, mix promptly with sucrose, hypromellose, aspartame, essence.Grading system: B.
Embodiment 4:
Rifaximin was pulverized 40 mesh sieves, mixed promptly with sucrose, hypromellose, aspartame, essence.Grading system: C.
Embodiment 5:
Rifaximin is washed with 28% ethyl acetate solution, stir 3 minutes after-filtration, dry under 40 ℃ of conditions, pulverized 40 mesh sieves, mix promptly with sucrose, hypromellose, aspartame, essence.Grading system: C.
Embodiment 6:
Rifaximin is washed with 28% acetone soln, stir 3 minutes after-filtration, dry under 40 ℃ of conditions, pulverized 40 mesh sieves, mix promptly with sucrose, hypromellose, aspartame, essence.Grading system: C.
Embodiment 7:
The Rifaximin dry suspension agent of embodiment 1 and embodiment 4 preparations is carried out the dissolution test respectively, investigate the difference of both dissolutions.The dissolution condition is: 2010 editions pharmacopeia of Chinese Pharmacopoeia, slurry method, 50rpm, dissolution medium: water 500ml, 37 ℃ of temperature.The investigation result is as follows:
| Dissolution % | Embodiment 1 | Execute example 4 |
| ??10min | ?71％ | ?70％ |
| ??20min | ?88％ | ?86％ |
| ??30min | ?95％ | ?94％ |
| ??45min | ?98％ | ?97％ |
Dissolution is no significant difference as a result.
As can be seen from the above results, Rifaximin dry suspension agent of the present invention, mouthfeel is good, does not have bitterness substantially, and dissolution is better, has finished the object of the invention.
As what it will be apparent to those skilled in the art that, can make many modifications and variations of the present invention and do not deviate from its spirit and scope.Specific embodiments described herein only provides in the mode of example, and gamut restriction the present invention of the equivalent that only is awarded together with these claim with claims.
Claims (6)
1. one kind prepares the method for almost not having the bitterness Rifaximin dry suspension agent, it is characterized in that rifaximin is passed through 20～35% (V/V) ethanol water washing.
2. the method for claim 1 is characterized in that rifaximin is passed through 25%～30% (V/V) ethanol water washing.
3. the method for claim 2 is characterized in that rifaximin by the washing of 28% (V/V) ethanol water.
4. each described method of claim 1 to 3 after the wherein said washing, be not higher than drying under 60 ℃ of conditions.
5. the method for claim 4 further comprises dried rifaximin is sieved to certain particle size, and with filler sucrose, suspending agent hydroxypropyl emthylcellulose, flavoring agent aspartame and essence mix, the preparation Rifaximin dry suspension agent.
6. the preparation method of claim 4, wherein preferably be not higher than under 40 ℃ the condition dry.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN201010177930A CN101836959A (en) | 2010-05-20 | 2010-05-20 | Method for preparing almost bitterless rifaximin dry suspension |
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| CN201010177930A CN101836959A (en) | 2010-05-20 | 2010-05-20 | Method for preparing almost bitterless rifaximin dry suspension |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102218078A (en) * | 2011-04-19 | 2011-10-19 | 南京威泰珐玛兽药研究所有限公司 | Rifaximin suspension containing montmorillonite and preparation method thereof |
| CN110623929A (en) * | 2019-09-17 | 2019-12-31 | 南京臣功制药股份有限公司 | Rifaximin dry suspension and preparation method thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1485034A (en) * | 2002-09-26 | 2004-03-31 | 天津合益达生物医学技术有限公司 | Rifaximin suspension mix granule formulation |
| CN1900077A (en) * | 2005-03-03 | 2007-01-24 | 阿尔法瓦塞尔曼有限公司 | New polymorphous forms of rifaximin, processes for their production and use thereof in the medicinal preparations |
| US20090234114A1 (en) * | 2003-11-07 | 2009-09-17 | Alfa Wasserman S.P..A. | Polymorphic forms alpha, beta, and gamma of rifaximin |
| CN101642439A (en) * | 2009-08-17 | 2010-02-10 | 扬州市三药制药有限公司 | Rifaximin dry suspension and production method thereof |
-
2010
- 2010-05-20 CN CN201010177930A patent/CN101836959A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1485034A (en) * | 2002-09-26 | 2004-03-31 | 天津合益达生物医学技术有限公司 | Rifaximin suspension mix granule formulation |
| US20090234114A1 (en) * | 2003-11-07 | 2009-09-17 | Alfa Wasserman S.P..A. | Polymorphic forms alpha, beta, and gamma of rifaximin |
| CN1900077A (en) * | 2005-03-03 | 2007-01-24 | 阿尔法瓦塞尔曼有限公司 | New polymorphous forms of rifaximin, processes for their production and use thereof in the medicinal preparations |
| CN101642439A (en) * | 2009-08-17 | 2010-02-10 | 扬州市三药制药有限公司 | Rifaximin dry suspension and production method thereof |
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| 《中国实用医药》 20080510 张等 对于口服药物掩味方法的研究进展 , 第13期 * |
| 《中国新药杂志》 20070808 于飞千等 药物制剂中苦味掩盖方法的研究进展 , 第15期 * |
| 《中国药学杂志》 20051108 柯学等 口腔崩解片及其制备技术进展 , 第11期 * |
| 《河北化工》 20090620 吴谧等 头孢呋辛酯掩味方法及颗粒剂的稳定性研究 , 第06期 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102218078A (en) * | 2011-04-19 | 2011-10-19 | 南京威泰珐玛兽药研究所有限公司 | Rifaximin suspension containing montmorillonite and preparation method thereof |
| CN102218078B (en) * | 2011-04-19 | 2012-10-10 | 南京威泰珐玛兽药研究所有限公司 | Rifaximin suspension containing montmorillonite and preparation method thereof |
| CN110623929A (en) * | 2019-09-17 | 2019-12-31 | 南京臣功制药股份有限公司 | Rifaximin dry suspension and preparation method thereof |
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Application publication date: 20100922 |