CN101019876B - Compound roxithromycin dispersing tablet - Google Patents
Compound roxithromycin dispersing tablet Download PDFInfo
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- CN101019876B CN101019876B CN200610007513A CN200610007513A CN101019876B CN 101019876 B CN101019876 B CN 101019876B CN 200610007513 A CN200610007513 A CN 200610007513A CN 200610007513 A CN200610007513 A CN 200610007513A CN 101019876 B CN101019876 B CN 101019876B
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Abstract
The present invention discloses one kind of compound roxithromycin dispersing tablet and its preparation process. The compound roxithromycin dispersing tablet contains roxithromycin and ambroxol hydrochloride in the weight ratio of 3-6 to 1-2. The compound roxithromycin dispersing tablet is prepared via adding disintegrant, such as crossed polyvidone, medicinal surfactant, such as sodium dodecyl sulfate, excellent filler, such as microcrystal cellulose, and good adhesive; wet or dry pelletizing and tabellting. It has excellent forming effect and quick disintegrating to generate curative effect.
Description
Technical field: the present invention relates to a kind of medicine dispersible tablet, especially relate to a kind of Roxithromycin and ambroxol hydrochloride compound dispersible tablet and preparation technology thereof.
Background technology: pulmonary bacterial is commonly encountered diseases, the frequently-occurring disease of respiratory system, and main clinical manifestation generally adopts antibiotic therapies based on cough, expectoration more.But in the more bacterial respiratory tract infection case of some amounts of expectoration, though reasonably used antibacterials, still can not get ideal curative effect sometimes, its reason may not obtain unobstructed drain relevant with sputum.Pulmonary is a highly dabbling organ, in general, similar in the concentration of antibacterials in lung and the blood plasma, yet blood is difficult to perfusion in the vomica of abscess and in the bronchial secretions, medicine peak concentration there concentration in the blood plasma, pathogenic bacterium forgoes can not rely on antibacterials but depend on unobstructed drain and discharges in the sputum.The expectoration reaction of human body instinct is cough.Cough is a kind of intensive expiration percussion action, itself has duality: it can help to remove foreign body and the interior various stimulating factors of respiratory tract that enter respiratory tract, impel the sputum that produces in the respiratory tract to discharge smoothly, thereby can alleviate disease, this is a favourable aspect.But cough also has disadvantageous one side to human body.It can make the infection diffusion in the respiratory tract, and long-term violent cough is a factor impelling other disease to form, and frequent cough can cause vomiting, and influences the absorption of nutrition, and influence is had a rest, sleep, consumes one's strength, and influences the resistance against diseases of human body.Therefore, effective treatment of pulmonary infection should comprise that reasonably antibacterial therapy eliminates the phlegm with effective medicine.
Macrolide antibiotics Roxithromycin and expelling phlegm drugs ambroxol hydrochloride are formed compound preparation, can effectively treat the bacillary acute bronchitis that causes by sensitive microbial, chronic bronchitis acute exacerbation, bronchopneumonia, typicality pathogen pneumonia, merge bronchial asthma or bronchiectasis, sinusitis and the otitis media etc. of bacterial infection.Roxithromycin and ambroxol hydrochloride in clinical practice early, curative effect is clear and definite, two medicine couplings have potentiation.
The mechanism of action of Roxithromycin is to combine with bacterial ribosome 50S subunit, suppresses the protein synthesis in the bacterial cell and plays a role.And can penetrate phagocyte and enter in the cell, having superiority to infecting in the treatment antibacterial, its antimicrobial spectrum and erythromycin are close.Mainly act on gram positive bacteria, anaerobe, chlamydia and mycoplasma etc.
Ambroxol hydrochloride is a mucolytic agent, can increase the secretion of respiratory mucosa serous gland, reduces the mucous gland secretion, thereby reduces sputum viscosity; To acute and chronic tracheitis patient, oral or suction this product can obviously reduce cough and dyspnea, improve expectoration, and has a multiple effect that promotes pulmonary surfactant and secretion of air flue liquid and ciliary movement, increase the bronchus ciliary movement, effective to some actute infection symptom of alleviating otorhinolaryngology.
But Roxithromycin belongs to concentration dependent form antibiotic, and antibacterial effect and drug concentrations are closely related, and the ordinary preparation that exists in the prior art often slowly influences the abundant absorption of medicine because of disintegrate and stripping, thereby is difficult to reach desirable therapeutic.
For example, Chinese patent application CN1698640A discloses a kind of Roxithromycin of children taking and compounding powder of ambroxol hydrochloride of being suitable for, be by pharmaceutic adjuvants such as Roxithromycin and ambroxol hydrochloride and magnesium oxide, sodium lauryl sulphate, hyprolose, xanthan gum, spice, aspartame, sucrose being made for the compound roxithromycin powder of granule form, but this powder needs a large amount of eliminating cold for resuscitation water dissolution medicines when taking, not only reduced drug level, cause bioavailability of medicament to reduce, take difficulty but also cause.
Chinese patent application CN1582954A discloses the compound preparation of a kind of Roxithromycin and ambroxol hydrochloride, its concrete disclosed dosage form has capsule and tablet, but the compound roxithromycin of this conventional capsule and tablet form, dissolving is comparatively slow in the body of oral back, and be difficult to reach fully dissolving, cause bioavailability of medicament to reduce, can not obtain ideal antibacterial effect.
Summary of the invention: in order to solve the above-mentioned problems in the prior art, the inventor is by further investigation, can prepare compound roxithromycin dispersing tablet by a kind of special preparation technology, this dispersible tablet has wonderful rapid release and solubility property, can make blood drug level maintain higher level after taking fast and stable, thereby obtain beyond thought antibacterial effect.Therefore, the invention provides a kind of compound roxithromycin dispersing tablet, its performance and antibacterial effect are higher than the ordinary preparation of compound roxithromycin far away.
In recent years, the oral preparation of quick releasing development is rapid, and according to statistics, world's quick releasing formulation sales volume was nearly 200,000,000 dollars in 1996.Dispersible tablet wherein is because taking convenience absorbs soon, and characteristics such as bioavailability height are subjected to people's attention day by day.Dispersible tablet mean can be in water rapidly disintegrate become the tablet of uniform viscosity suspension.Dispersible tablet has advantages such as dosage is accurate, volume is little, transportation is easy to carry as conventional tablet, and preparation technology and working condition all do not have specific (special) requirements, just can produce in common tablet workshop.But its disintegrate and dissolution rate are faster than conventional tablet, have flexile instructions of taking again simultaneously: can swallow as the conventional tablet water, also can earlier it be dispersed in water or the beverage and take, especially be fit to old man, child and the patient of difficulty that swallows.
Roxithromycin is a poorly water soluble drugs, and it is made dispersible tablet with ambroxol hydrochloride, can obviously improve the dissolving out capability of medicine, improves its curative effect; Ambroxol hydrochloride and Roxithromycin half-life are very approaching, can produce good synergism, can promote Roxithromycin to penetrate respiratory secretions better, and respiratory tract disease is better treated.
Therefore, the invention provides a kind of compound roxithromycin dispersing tablet, it is characterized in that, this dispersible tablet contains Roxithromycin and ambroxol hydrochloride as active component, and wherein the weight ratio of Roxithromycin and ambroxol hydrochloride is 6～3: 1～2, preferred 6～4: 1～1.5, further preferred 5～4: 1～1.2, most preferably 5: 1.
Preferably, also contain pharmaceutic adjuvant in the compound roxithromycin dispersing tablet of the present invention, and this adjuvant is one or more the mixture that is selected from medicinal surfactant, disintegrating agent, filler, binding agent and the lubricant.
Wherein pharmaceutically useful surfactant is selected from one or more the mixture in sodium lauryl sulphate, Tween 80, sucrose ester and the poloxamer, and its content accounts for 0.5～15% of dispersible tablet gross weight.
Pharmaceutical acceptable disintegrants is selected from one or more the mixture in polyvinylpolypyrrolidone, carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose, cross-linking sodium carboxymethyl cellulose, the carboxymethylcellulose calcium, and its content accounts for 5～30% of dispersible tablet gross weight.
Pharmaceutically useful filler is selected from lactose, microcrystalline Cellulose, pregelatinized Starch, sodium bicarbonate and the starch one or more mixture, and its content accounts for 40～75% of dispersible tablet gross weight.
Pharmaceutically useful binding agent is selected from one or more the mixture in polyvidone, polyvinyl pyrrolidone-vinyl acetate copolymer and the hypromellose, and its content accounts for 0.5～5% of dispersible tablet gross weight.
Pharmaceutically useful lubricant is selected from one or more the mixture in magnesium stearate, Pulvis Talci, the micropowder silica gel, and its content accounts for 0.5～5% of dispersible tablet gross weight.
More preferably, dispersible tablet of the present invention can also further contain other pharmaceutic adjuvants such as correctives, high molecular polymer, sweeting agent such as spice.
The characteristics of dispersible tablet of the present invention are disintegrate rapidly in water, homodisperse and can sieve by No. 2.And its dissolution in vitro can reach more than 80% within 15 minutes.Concrete data see result of the tests such as dissolution appended among each embodiment, dispersing uniformity for details.
Compound roxithromycin dispersing tablet of the present invention can adopt any technology in wet granulation technology, dry granulation technology and the direct compression technology to be prepared.
Dispersing uniformity is checked: according to " the dispersing uniformity algoscopy of dispersible tablet under two appendix I of Chinese pharmacopoeia version in 2005 A tablet item.Get 2 of dispersible tablets, put jolting in the 100ml water, in 20 ℃ ± 1 ℃ water, 3 minutes all disintegrate and by No. 2 the sieve.
Dissolution test:
" under Chinese pharmacopoeia two roxithromycin dispersing tablets of version in 2005 and the ambroxol hydrochloride sheet item, all selecting hydrochloric acid solution 900ml is dissolution medium, adopts the dissolution of sulphuric acid colour developing ultraviolet spectrophotometry and determined by ultraviolet spectrophotometry roxithromycin dispersing tablet and ambroxol hydrochloride sheet respectively.If adopt the dissolution of determined by ultraviolet spectrophotometry compound roxithromycin dispersing tablet, need to measure respectively, complicated operation need dilute repeatedly.In addition, discover that through the inventor Roxithromycin is unstable in hydrochloric acid solution, have 50% Roxithromycin to degrade approximately, and sulphuric acid can show same color to Roxithromycin and its catabolite, measurement error is bigger.So this dissolution determination method can not embody the true stripping quantity of Roxithromycin well.Therefore, the phosphate buffer (pH5.8) that the inventor selects Roxithromycin and ambroxol hydrochloride all can stablize stripping according to bibliographical information is a dissolution medium, and " method of two roxithromycin dispersing tablet HPLC of Chinese pharmacopoeia version in 2005 method mensuration content detects the dissolution of Roxithromycin and ambroxol hydrochloride simultaneously in employing.This method is measured the dissolution of two principal agents in this product simultaneously, and is more simple and efficient, and selectivity is better, and sensitivity is higher.
Concrete grammar is as follows:
By " 2005 editions two appendix XC dissolution methods of Chinese Pharmacopoeia, second method: put into 1 of this product for every glass, as dissolution medium, operate in accordance with the law with phosphate buffer (pH5.8) 900ml.In 15min sampling 5ml, filter with filter membrane (aperture must not greater than 0.45 μ m), abandon filtrate just, get subsequent filtrate, as need testing solution.Other gets Roxithromycin reference substance 150mg and ambroxol hydrochloride reference substance 30mg, and accurate the title decides, and puts in the 100ml measuring bottle, adds dehydrated alcohol and makes it dissolving in right amount, adds the stripping medium to scale, shakes up.Precision is measured above-mentioned solution 1ml and is put in the 10ml measuring bottle, adds the stripping medium to scale, shakes up, in contrast product solution.Measure the dissolution of two principal agents simultaneously with the HPLC method.
The specific embodiment
Provide the exemplary embodiments of compound roxithromycin dispersing tablet of the present invention below, be appreciated that these embodiment only are used to further specify the present invention, and do not constitute any restriction protection domain of the present invention.
Embodiment 1
Dispersible tablet prepares according to following prescription
1. fill a prescription
Roxithromycin 150 grams
Ambroxol hydrochloride 30 grams
Starch 280 grams
L-hydroxypropyl cellulose 20 grams
Tween 80 5 grams
1% hypromellose alcoholic solution is an amount of
Magnesium stearate 5 grams
Make 1000
2. preparation method
1) respectively Roxithromycin, ambroxol hydrochloride, starch, L-hydroxypropyl cellulose, sodium lauryl sulphate are pulverized, crossed 120 mesh sieves, with the abundant mix homogeneously of above-mentioned supplementary material, standby.
2) preparation of binding agent: the alcoholic solution of getting full dose adds hypromellose and tween 80 while stirring, is stirred to dissolving fully, and is standby.
3) with 1) in powder with 2) in binding agent system soft material, cross 18 mesh sieves and granulate, 40 ℃ of dryings are crossed 18 mesh sieve granulate, add polyvinylpolypyrrolidone, magnesium stearate mix homogeneously, tabletting, promptly.
3. check
1) dispersing uniformity: up to specification.
2) dissolution:
Embodiment 2
Dispersible tablet is prepared from by following prescription
1. fill a prescription
Roxithromycin 150 grams
Ambroxol hydrochloride 30 grams
Lactose 250 grams
Sucrose ester 5 grams
Polyvinyl pyrrolidone-vinyl acetate copolymer 5 grams
Cross-linking sodium carboxymethyl cellulose 15 grams
Magnesium stearate 5 grams
Make 1000
2. preparation method
1) respectively Roxithromycin, ambroxol hydrochloride, lactose, carboxymethyl starch sodium, polyvinyl pyrrolidone-vinyl acetate copolymer are pulverized, crossed 120 mesh sieves, sucrose ester and poloxamer are crossed 80 mesh sieves, and be with the abundant mix homogeneously of above-mentioned supplementary material, standby.
2) above-mentioned mixed-powder is used dry granulation mechanism grain, added cross-linking sodium carboxymethyl cellulose, magnesium stearate mix homogeneously, tabletting, promptly.
3. check
1) dispersing uniformity: up to specification.
2) dissolution:
Dispersible tablet is prepared from by following prescription
1. fill a prescription
Roxithromycin 150 grams
Ambroxol hydrochloride 30 grams
Microcrystalline Cellulose 240 grams
Sodium lauryl sulphate 5 grams
Polyvidone 5 grams
Magnesium stearate 5 grams
Make 1000
2. preparation method
Respectively Roxithromycin, ambroxol hydrochloride, sodium bicarbonate, sodium lauryl sulphate are pulverized, crossed 120 mesh sieves, all the other adjuvants are crossed 80 mesh sieves, with the abundant mix homogeneously of above-mentioned supplementary material, and tabletting, promptly.
3. check
1) dispersing uniformity: up to specification.
2) dissolution:
Embodiment 4
The compound roxithromycin dispersing tablet of embodiment 1 preparation and commercially available roxithromycin dispersing tablet are carried out the dissolution contrast test, the results are shown in accompanying drawing.
Claims (1)
1. a compound roxithromycin dispersing tablet is characterized in that, it is composed as follows to fill a prescription:
Roxithromycin 150 grams
Ambroxol hydrochloride 30 grams
Starch 280 grams
L-hydroxypropyl cellulose 20 grams
Tween 80 5 grams
1% hypromellose alcoholic solution is an amount of
Polyvinylpolypyrrolidone 15 grams
Magnesium stearate 5 grams
Make 1000
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN200610007513A CN101019876B (en) | 2006-02-13 | 2006-02-13 | Compound roxithromycin dispersing tablet |
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| Application Number | Priority Date | Filing Date | Title |
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| CN200610007513A CN101019876B (en) | 2006-02-13 | 2006-02-13 | Compound roxithromycin dispersing tablet |
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| CN101019876A CN101019876A (en) | 2007-08-22 |
| CN101019876B true CN101019876B (en) | 2010-05-12 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104688757A (en) * | 2013-12-09 | 2015-06-10 | 海南澳美华制药有限公司 | Dissolution rate increased erythromycin cydocarbonate oral composition |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101862303B (en) * | 2009-04-17 | 2014-03-19 | 北京以岭生物工程技术有限公司 | Roxithromycin sustained release tablets and preparation method thereof |
| CN102358749B (en) * | 2011-10-27 | 2013-07-24 | 山东罗欣药业股份有限公司 | Roxithromycin ambroxol tablet composite and preparing method thereof |
| CN103720668B (en) * | 2012-10-10 | 2016-06-08 | 华东理工大学 | The tablet of a kind of quick release Isoforskolin |
| CN104784132B (en) * | 2014-01-17 | 2019-04-09 | 南京海鲸药业有限公司 | A kind of clarithromycin composition |
| CN103977016B (en) * | 2014-05-19 | 2016-03-02 | 海南葫芦娃制药有限公司 | A kind of compound roxithromycin dispersing tablet and preparation method thereof |
| CN110548010A (en) * | 2019-04-02 | 2019-12-10 | 海南海神同洲制药有限公司 | preparation method of roxithromycin dispersible tablet |
| CN115501196B (en) * | 2022-10-31 | 2023-04-11 | 江苏神龙药业有限公司 | Preparation method of roxithromycin dispersible tablet |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1582954A (en) * | 2004-06-11 | 2005-02-23 | 营口奥达制药有限公司 | Composition of roxithromycin and ambroxol |
| CN1698640A (en) * | 2005-06-01 | 2005-11-23 | 李�杰 | Compound powder of Roxithromycin and ambroxol hydrochloride sustained adequate for children, its prescription and preparation method |
-
2006
- 2006-02-13 CN CN200610007513A patent/CN101019876B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1582954A (en) * | 2004-06-11 | 2005-02-23 | 营口奥达制药有限公司 | Composition of roxithromycin and ambroxol |
| CN1698640A (en) * | 2005-06-01 | 2005-11-23 | 李�杰 | Compound powder of Roxithromycin and ambroxol hydrochloride sustained adequate for children, its prescription and preparation method |
Non-Patent Citations (5)
| Title |
|---|
| Meiling Qi et al.Simultaneous determination of roxithromycin and ambroxolhydrochloride in a new tablet formulation by liquidchromatography.Journal of Pharmaceutical and Biomedical Analysis35.2004,351287-1291. * |
| 冯萍 等.罗红霉素分散片人体相对生物利用度研究.中国抗生素杂志25 3.2000,25(3),207-213. |
| 冯萍等.罗红霉素分散片人体相对生物利用度研究.中国抗生素杂志25 3.2000,25(3),207-213. * |
| 彭礼明，，2005年，第2卷第3期，第页.分散片处方、工艺特点及其进展.药品评价2 3.2005,2(3),230-233. |
| 彭礼明,2005年,第2卷第3期,第页.分散片处方、工艺特点及其进展.药品评价2 3.2005,2(3),230-233. * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104688757A (en) * | 2013-12-09 | 2015-06-10 | 海南澳美华制药有限公司 | Dissolution rate increased erythromycin cydocarbonate oral composition |
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