CN101502513A - Rifaximin sustained-release preparation composition and method for preparing the same - Google Patents
Rifaximin sustained-release preparation composition and method for preparing the same Download PDFInfo
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- CN101502513A CN101502513A CNA2008102155139A CN200810215513A CN101502513A CN 101502513 A CN101502513 A CN 101502513A CN A2008102155139 A CNA2008102155139 A CN A2008102155139A CN 200810215513 A CN200810215513 A CN 200810215513A CN 101502513 A CN101502513 A CN 101502513A
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Abstract
The invention discloses a rifaximin sustained-release preparation combination and a preparation method thereof. The rifaximin sustained-release preparation combination is mainly prepared from rifaximin bulk drugs, sustained-release materials and other appropriate auxiliary materials. The rifaximin sustained-release preparation provided by the invention can deaccelerate the release rate of the main drugs, reduce the frequency of administration and improve the patient compliance. The invention provides a novel form of drug having better patient compliance and having the advantages of high quality controllability and stability of the preparation process.
Description
Technical field
The invention belongs to medical technical field, relate to a kind of Rifaximin sustained-release preparation composition and preparation method thereof.
Background technology
The intestinal organ can be subjected to the influence of many inflammatory diseasess, is generally inflammatory bowel.Particularly, crohn is serious chronic inflammatory disease, the multiple level, the particularly existence that all can observe the existence of this disease and also can observe this disease in the mucosa and the anal regions of colon sometimes at rear section, ileum, colon or ileum and the colon of small intestinal of this sickness influence digestive tract (from mouth to anus).In the intestinal part of paying close attention to, inflammation, swelling and ulcer can appear at whole intestinal wall, cause narrow, hemorrhagic ulcer and pain, and unaffected part present normally.The alternate cycle of the inflammatory symptoms of the different orders of severity appears in crohn, described symptom for example: suffer from diarrhoea, suffer from abdominal pain, lose weight, often with chapping or periproctic fistula.2/3 to 3/4 the patient who suffers from crohn needs operation sometime its all one's life.Operation is used to alleviate not to be had the symptom of response or eliminates complication therapeutic treatment, and described complication is intestinal obstruction, intestinal perforation, intestinal abscess or enterorrhagia for example.
For the pharmaceutical preparation that is used for the treatment of inflammatory bowel (for example gastrointestinal disease Neo-Confucianism), the general antibiotic of using more, it has one or more following features: intestinal level activity, low absorb, the probability of the wide spectrum effect of the control of enteric cavity bacteria levels, antimicrobial (for example intestinal Gram-positive, Gram-negative, aerobic and anaerobism component), the long-term treatment that has no side effect, reduce use with promote compliance (even to the needs of potential high dose, for example long-term dosage and/or every day multiple dose).
Rifaximin has a plurality of features in these features as non-aminoglycosides intestinal antibiotic.It suppresses the synthetic of bacteria RNA, and effect is strong, has a broad antifungal spectrum.It is to the aurococcus in the Gram-positive aerobe, staphylococcus epidermidis and streptococcus faecalis; Bacteroides in Salmonella in the gram-negative aerobic bacteria, escherichia coli, Shigella, yersinia enterocolitica, coccus and the gram-negative anaerobic bacteria all there is high activity, clinically be mainly used in acute and chronic intestinal infection due to Gram-positive and feminine gender, the aerobic and anaerobe, the diarrhoea syndrome, diarrhoea due to intestinal microbial population changes, reach the prophylactic of postoperative intestinal, hyperammonemia, portal system encephalitis, hepatic coma before the art; Be used for skin infection; Can also be used for bacterial vaginosis.
In fact the rifaximin oral administration does not absorb, and only acts on the gastrointestinal tract part, and high concentration is arranged in intestinal, is not present in other organs, more safer than other antibiotic.
Present existing rifaximin oral formulations has only conventional tablet, capsule and dry suspension, and specification is 100mg, 200mg.The clinical practice of rifaximin has following deficiency: be used for the treatment of crohn, dosage is 600mg/ days, used for 16 weeks (as shafran, I., Am.J.Gastroenterol., 2003,98 (Suppl.) S-250 is described), this just need every day at the most six used 3 months, repeatedly take medicine every day, this can cause relatively poor patient's compliance.
For this reason, we are through exploring repeatedly, developed one group of Rifaximin sustained-release preparation composition, the advantage of this slow release formulation is: the rate of release that can delay medicine, reduce the number of times of taking of medicine, improve compliance of patients, the blood drug level of remaining valid, improve curative effect, reduce side effect, reduce medical expense.
Show through relevant patent and prior art literature search result, there is no the relevant report of Rifaximin sustained-release preparation composition.
Summary of the invention
Repeatedly take medicine every day in order to overcome rifaximin, cause relatively poor shortcomings such as patient's compliance, the invention provides Rifaximin sustained-release preparation.It can delay the rate of release of medicine, reduces the number of times of taking of medicine, improves compliance of patients, and the blood drug level of remaining valid improves curative effect, reduces side effect, reduces medical expense.
The object of the present invention is to provide a kind of Rifaximin sustained-release preparation composition and preparation method thereof.
Technical scheme of the present invention is: a kind of Rifaximin sustained-release preparation composition and preparation method thereof is characterized in that: the said preparation compositions contains following composition by weight percentage:
100 parts of rifaximins
5～200 parts of slow-release materials
0～600 part of other adjuvant;
The Rifaximin sustained-release preparation composition specification is 50～3000mg.
Described rifaximin crude drug comprises the rifaximin or the original shape of one or more polymorphic forms; Wherein the rifaximin polymorphic forms is selected from form α, form β, form γ or form δ.
Described slow-release material is selected from one or more in the following material: the solubility/insoluble salt of hydroxypropyl emthylcellulose, Cellulose ethyl hydroxypropyl ether, methylcellulose, ethyl cellulose, hydroxyethyl-cellulose, cellulose acetate, polyvinylpyrrolidone, polycarboxy ethene, sodium carboxymethyl cellulose, polyvinyl alcohol, Rikemal B 200, alginic acid etc.
Described Rifaximin sustained-release preparation composition also can further contain adjuvant commonly used in the pharmaceuticals industry, as filler, disintegrating agent, porogen, binding agent, lubricant, solubilizing agent, emulsifying agent, plasticizer, foaming agent, bleach activator, solvent etc.
Described binding agent is selected from one or more in the following material: starch, gelatin, sugar (as sucrose, glucose, dextrose, lactose etc.), rubber polymer, sodium alginate, hydroxy methocel, methylcellulose, polyvinylpyrrolidone, Polyethylene Glycol, ethyl cellulose, water, wax, alcohol etc.
Described solubilizing agent can be selected one or more of tartaric acid, citric acid, Polyethylene Glycol for use; Emulsifying agent can select for use span80 one or more of span85; Porogen can be selected one or more of saccharide, mannitol, starch, Pulvis Talci, silicon dioxide, water soluble salt etc. for use.
Described foaming agent can adopt basic magnesium carbonate, sodium bicarbonate etc.; Described bleach activator can adopt hexadecanol, octadecanol, Cera Flava etc.; Described solvent can adopt dehydrated alcohol, acetone, ethanol, water etc.
Described lubricant can be selected from one or more in the following material: Pulvis Talci, magnesium stearate, calcium stearate, stearic acid, hydrogenated vegetable oil, Polyethylene Glycol etc.
Described plasticizer can be selected from least a in propylene glycol, glycerol, Polyethylene Glycol, triacetin, acetyl list monoglyceride, phthalic acid ester, the Semen Ricini wet goods.
The granulation of the related oral slow-releasing preparation of the present invention can be passed through the moulding process of corresponding preparations, the oral slow-releasing preparation that gets final product correspondingly then by existing granulating process preparation such as dry method, wet method, spray drying, centrifugal granulating.
Rifaximin sustained-release preparation composition preparation method:, wrap slow-release material again and make slow releasing tablet and sustained-release granular formulation at the plain sheet or the crude granule of molding; Perhaps slow-release material is incorporated into as the skeleton of slow release in other adjuvants of molding by dry method or wet granulation technology preparation, granulation after drying, granulate become granule or further tabletting, promptly get slow releasing tablet and sustained-release granular formulation.Slow releasing capsule can be made compositions the suitable hybrid particles that contains slow-release material and be filled in the common hard capsule; Or mixture such as rifaximin, binding agent are made the pastille micropill, and again the pastille micropill is made slow-release micro-pill with the slow-release material coating, be filled into and promptly get the sustained-release micro-pill capsules agent in the common hard capsule.
Rifaximin sustained-release novel form provided by the invention can delay the rate of release of principal agent, reduces the number of times of taking of medicine, improves compliance of patients.
Rifaximin sustained-release novel form preparation technology's quality controllability provided by the invention and good stability.
The specific embodiment
Embodiment 1
Slow releasing tablet
Prescription:
Preparation technology:
Cross behind 80 mesh sieves rifaximin, hydroxypropyl emthylcellulose, microcrystalline Cellulose, magnesium stearate standby respectively; take by weighing rifaximin, hydroxypropyl emthylcellulose, microcrystalline Cellulose by recipe quantity and put mixing in the mixer, it is an amount of to add 80% ethanol, granulates, granulate; 45 ℃ of dry 30min; dried granule adds the magnesium stearate mixing of recipe quantity, crosses 16 eye mesh screen granulate with oscillating granulator, and granule is carried out assay; and the heavy scope of definite sheet; tabletting, drying is packed after the passed examination.
Zhi Bei Rifaximin sustained-release sheet as stated above meets the requirement of coherent detection project of regulation in " Chinese Pharmacopoeia 2005 version two ones " ' rules of preparations '.
Embodiment 2
Slow releasing tablet
Prescription: plain sheet
Prescription: sustained release coating liquid
25 parts of hydroxypropyl emthylcelluloses
10 parts of ethyl celluloses
5 parts of propylene glycol
6 parts of titanium dioxide
4 parts of Pulvis Talci
2% ethyl cellulose ethanol liquid is an amount of
Preparation technology:
Rifaximin, polyvinylpyrrolidone, starch, lactose, magnesium stearate are crossed 100 mesh sieves respectively; take by weighing rifaximin, polyvinylpyrrolidone, starch, lactose by recipe quantity; put mixing in the mixer; it is an amount of to add 80% ethanol; granulate; 45 ℃ of dry 30min; dried granule adds the magnesium stearate mixing of recipe quantity; cross 16 eye mesh screen granulate with oscillating granulator, granule is carried out assay, and the heavy scope of definite sheet; tabletting gets plain sheet; be equipped with coating solution by sustained release coating liquid prescription plain sheet is carried out coating, after the passed examination, packing.
Zhi Bei Rifaximin sustained-release sheet as stated above meets the requirement of coherent detection project of regulation in " Chinese Pharmacopoeia 2005 version two ones " ' rules of preparations '.
Embodiment 3
Slow releasing capsule
Prescription:
Preparation technology:
Rifaximin, hydroxypropyl emthylcellulose, ethyl cellulose, lactose, magnesium stearate are crossed 80 mesh sieves respectively; take by weighing rifaximin, hydroxypropyl emthylcellulose, ethyl cellulose, lactose, magnesium stearate by recipe quantity; put mix homogeneously in the mixer; 4% polyvinylpyrrolidone alcoholic solution is made soft material in right amount, granulates in granulation machine.With the above-mentioned granule that makes in 60 ℃ of dry 1.5h.Again by oscillating granulator, with 20 eye mesh screen granulate.Hybrid particles is carried out assay, and determine common hard capsule case range of capacity filling, pack after the passed examination.
Zhi Bei Rifaximin sustained-release capsule as stated above meets the requirement of coherent detection project of regulation in " Chinese Pharmacopoeia 2005 version two ones " ' rules of preparations '.
Embodiment 4
Sustained-release micro-pill capsules
Prescription: crude granule
Prescription: sustained release coating liquid
15 parts of hydroxypropyl emthylcelluloses
3 parts of propylene glycol
2 parts of titanium dioxide
1 part of sodium lauryl sulphate
2 parts of Pulvis Talci
Water is an amount of
Preparation technology:
Rifaximin, polyvinylpyrrolidone, microcrystalline Cellulose, cane sugar powder, magnesium stearate are crossed 100 mesh sieves respectively; take by weighing rifaximin, polyvinylpyrrolidone, microcrystalline Cellulose, cane sugar powder, magnesium stearate by recipe quantity; place the centrifugal granulator machine; spray into 80% ethanol system crude granule; be equipped with coating solution by sustained release coating liquid prescription crude granule is carried out coating; coated granule is carried out assay, determine common hard capsule case range of capacity filling.After the passed examination, packing.
Zhi Bei Rifaximin sustained-release pellet capsule as stated above meets the requirement of coherent detection project of regulation in " Chinese Pharmacopoeia 2005 version two ones " ' rules of preparations '.
Embodiment 5
Sustained-release granular formulation
Prescription:
Preparation technology:
Rifaximin, Cellulose ethyl hydroxypropyl ether, ethyl cellulose, starch, magnesium stearate are crossed 80 mesh sieves respectively; take by weighing rifaximin, Cellulose ethyl hydroxypropyl ether, ethyl cellulose, starch, magnesium stearate by recipe quantity; put mix homogeneously in the mixer; 30% polyvinylpyrrolidone alcoholic solution is made soft material in right amount, granulates in granulation machine.With the above-mentioned granule that makes in 60 ℃ of dry 1.5h.Again by oscillating granulator, with 20 eye mesh screen granulate.Granule is carried out assay, pack after the passed examination.
Zhi Bei Rifaximin sustained-release granule as stated above meets the requirement of coherent detection project of regulation in " Chinese Pharmacopoeia 2005 version two ones " ' rules of preparations '.
Embodiment 6
Sustained-release granular formulation
Prescription: crude granule
Prescription: sustained release coating liquid
30 parts of hydroxypropyl emthylcelluloses
5 parts of propylene glycol
6 parts of titanium dioxide
4 parts of Pulvis Talci
2% ethyl cellulose ethanol liquid is an amount of
Preparation technology:
Rifaximin, polyvinylpyrrolidone, starch, lactose, magnesium stearate are crossed 100 mesh sieves respectively; take by weighing rifaximin, polyvinylpyrrolidone, starch, lactose, magnesium stearate by recipe quantity; place the centrifugal granulator machine; spray into 80% ethanol system crude granule; be equipped with coating solution by sustained release coating liquid prescription crude granule is carried out coating; coated granule is carried out assay, after the passed examination, packing.
Zhi Bei Rifaximin sustained-release granule as stated above meets the requirement of coherent detection project of regulation in " Chinese Pharmacopoeia 2005 version two ones " ' rules of preparations '.
Claims (9)
1, a kind of Rifaximin sustained-release preparation composition and preparation method thereof is characterized in that: the said preparation compositions contains following composition by weight percentage:
100 parts of rifaximins
5～200 parts of slow-release materials
0～600 part of other adjuvant;
The Rifaximin sustained-release preparation composition specification is 50～3000mg;
The Rifaximin sustained-release preparation composition preparation method: necessary relevant auxiliary materials is made the plain sheet or the crude granule of molding by corresponding technology with rifaximin and corresponding preparations molding the time, wraps slow-release material again and makes slow releasing tablet and sustained-release granular formulation; Perhaps slow-release material is incorporated in other required adjuvants of molding by existing granulating process preparation as the skeleton of slow release, granulation after drying, granulate become granule or further tabletting, promptly get slow releasing tablet and sustained-release granular formulation.Slow releasing capsule can be made compositions the suitable hybrid particles that contains slow-release material and be filled in the hard capsule; Or mixture such as rifaximin, binding agent are made the pastille micropill by corresponding preparation technology, and again the pastille micropill is made sustained-release microparticle with the slow-release material coating, be filled into and promptly get the sustained-release micro-pill capsules agent in the hard capsule.
2, described according to claim 1, it is characterized in that rifaximin comprises one or more polymorphic forms rifaximin or original shapes; Wherein the rifaximin polymorphic forms is selected from form α, form β, form γ or form δ.
3, described according to claim 1, it is characterized in that adjuvant is filler, disintegrating agent, porogen, binding agent, lubricant, solubilizing agent, emulsifying agent, plasticizer, foaming agent, bleach activator, solvent etc.
4, described according to claim 1, it is characterized in that slow-release material is selected from one or more in the following material: the solubility/insoluble salt of hydroxypropyl emthylcellulose, Cellulose ethyl hydroxypropyl ether, methylcellulose, ethyl cellulose, hydroxyethyl-cellulose, cellulose acetate, polyvinylpyrrolidone, polycarboxy ethene, sodium carboxymethyl cellulose, polyvinyl alcohol, Rikemal B 200, alginic acid etc.
5, adjuvant according to claim 3 is characterized in that: binding agent wherein is selected from one or more in the following material: starch, gelatin, sugar (as sucrose, glucose, dextrose, lactose etc.), rubber polymer, sodium alginate, hydroxy methocel, methylcellulose, polyvinylpyrrolidone, Polyethylene Glycol, ethyl cellulose, water, wax, alcohol etc.
6, adjuvant according to claim 3 is characterized in that: wherein solubilizing agent can be selected one or more of tartaric acid, citric acid, Polyethylene Glycol etc. for use; Emulsifying agent can select for use span80 one or more of span85 etc.; Porogen can be selected one or more of saccharide, mannitol, starch, Pulvis Talci, silicon dioxide, water soluble salt etc. for use.
7, adjuvant according to claim 3 is characterized in that: wherein lubricant can be selected from one or more in the following material: Pulvis Talci, magnesium stearate, calcium stearate, stearic acid, hydrogenated vegetable oil, Polyethylene Glycol etc.
8, adjuvant according to claim 3 is characterized in that: wherein plasticizer can be selected from medium at least a of propylene glycol, glycerol, Polyethylene Glycol, triacetin, acetyl list monoglyceride, phthalic acid ester, Oleum Ricini.
9, described according to claim 1, it is characterized in that in the described preparation method, the granulation of related preparations can be passed through the moulding process of corresponding preparations, the oral sustained release solubility preparation that gets final product correspondingly then by existing granulating process preparation such as dry method, wet method, spray drying, centrifugal granulating.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2008102155139A CN101502513A (en) | 2008-09-04 | 2008-09-04 | Rifaximin sustained-release preparation composition and method for preparing the same |
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| CNA2008102155139A CN101502513A (en) | 2008-09-04 | 2008-09-04 | Rifaximin sustained-release preparation composition and method for preparing the same |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105832691A (en) * | 2016-05-31 | 2016-08-10 | 深圳市健元医药科技有限公司 | Dulaglutide colon positioning sustained release preparation and preparation method thereof |
| US20200375959A1 (en) * | 2009-10-27 | 2020-12-03 | Lupin Limited | Solid dispersion of rifaximin |
| CN116018133A (en) * | 2020-06-26 | 2023-04-25 | 博士医疗爱尔兰有限公司 | Targeted release rifaximin compositions |
-
2008
- 2008-09-04 CN CNA2008102155139A patent/CN101502513A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20200375959A1 (en) * | 2009-10-27 | 2020-12-03 | Lupin Limited | Solid dispersion of rifaximin |
| CN105832691A (en) * | 2016-05-31 | 2016-08-10 | 深圳市健元医药科技有限公司 | Dulaglutide colon positioning sustained release preparation and preparation method thereof |
| CN105832691B (en) * | 2016-05-31 | 2018-10-02 | 深圳市健元医药科技有限公司 | A kind of degree draws glycopeptide site specific DDS for colon sustained release preparation and preparation method thereof |
| CN116018133A (en) * | 2020-06-26 | 2023-04-25 | 博士医疗爱尔兰有限公司 | Targeted release rifaximin compositions |
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Open date: 20090812 |