CN103251577A - Compound ambroxol hydrochloride composition troche and preparation method thereof - Google Patents
Compound ambroxol hydrochloride composition troche and preparation method thereof Download PDFInfo
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- CN103251577A CN103251577A CN2013101668010A CN201310166801A CN103251577A CN 103251577 A CN103251577 A CN 103251577A CN 2013101668010 A CN2013101668010 A CN 2013101668010A CN 201310166801 A CN201310166801 A CN 201310166801A CN 103251577 A CN103251577 A CN 103251577A
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Abstract
The invention relates to the field of medicines, and discloses a compound ambroxol hydrochloride composition troche. The medical effective components in 1000 grains comprise 7.0-8.0g of ambroxol hydrochloride, 1.5-2.5g of salbutamol sulfate, 70-80g of lactose, 15-25g of hydroxypropylcellulose, approriate amount of 3% hydroxypropyl methylcellulose aqueous liquor, 5-8g of crosslinked povidone and 0.5-1.5g of magnesium stearate. With the adoption of the compound preparation consisting of ambroxol hydrochloride and salbutamol, the troche has the function of expelling phlegm to arrest coughing and preventing asthma by the synergistic effect of ambroxol hydrochloride and salbutamol sulfate, so that cough symptom can be quickly relieved to accelerate sputum discharge. The ambroxol hydrochloride and salbutamol are combined in use to better control secreta accompanied with asthma and acute and chronic bronchitis as well as bronchospasm. Combination of ambroxol hydrochloride and salbutamol not only improves the lung function, but also increases the asymptomatic days of the patient, and improves the living quality of the patient. The invention further discloses a method for preparing the ambroxol hydrochloride composition troche. The method is simple in process and suitable for large-scale production, and process parameters are easily controlled.
Description
Technical field
The present invention relates to field of medicaments, disclose a kind of compound ambroxol hydrochloride composition tablet and preparation method thereof.
Background technology
Tracheitis, asthma are a kind of common respiratory tract diseases, and its sickness rate height, the oncoming force are fast, and the whole world has 300,000,000 people to suffer from this disease approximately at present, in China 3,000 ten thousand patients is arranged, and prevalence is about 0.5%-1.5%, and all is progressively ascendant trend every year; Persistent ailment when outbreak clinical manifestation is: cough with asthma, asthma, abundant expectoration, uncomfortable in chest, itching of the throat, dyspnea, cardiopalmus hyperhidrosis, seriously fidgety, stridulate sound, heart beating is disorderly, blood pressure drops even death by suffocation.Bronchial asthma is that a kind of increasing with airway reactivity is the air flue chronic inflammatory disease of characteristics.Evidence suggests that actute infection and asthma attack are closely related, and can influence the order of severity of asthma.General population's bronchial asthma sickness rate is 0.569%.Some clinical and result of the tests show: asthma can two kinds of form onsets, and a kind of is based on bronchial muscular spasm, shows as ictal dyspnea; Another then based on the airway inflammation stimulation, shows as intractable cough, and the latter becomes cough variant asthma.
Treatment present situation and common drug are as follows:
Bronchial asthma: (1) glucocorticoid; (2) β
2Receptor stimulating agent, anti-inflammatory treatment is first elected inhaled glucocorticoid.Advocate glucocorticoid and β at present
2The two share receptor stimulating agent and can better control asthma; drug combination not only improves pulmonary function; and the asymptomatic natural law of increase patient; improve patient's quality of life; there is not the incidence rate of adverse reaction of increasing; this is consistent with external relevant bibliographical information, and Dowlang points out: in the respiratory mucosa protection, use low concentration β respectively
2Receptor stimulating agent and low concentration glucocorticoid only have the criticality cytoprotection; Low concentration uses both and unite, even also can make cilium surface obtain being close to the invasion and attack of protecting to resist respiratory pathogen completely; (3) control release type theophylline, its acting duration long (12-24) hour, and constant release has significantly reduced the fluctuation of serum theophylline concentration, the poisoning danger and the futile treatment that is lower than valley concentration that are higher than peak concentration of avoiding fugitive preparation to occur often, and theophylline can produce antiinflammatory action when lower serum treatment concentration (less than 10mg), so the control release type theophylline has become and prevents and treats one of asthma medicine commonly used; (4) antihistaminic, asthmatic patient no matter stage of attack, catabasis all exist histamine receptor unbalance, i.e. H
2Receptor (H
2R) quantity minimizing function is low, and H
1Receptor (H
1Therefore R) quantity increases, and function is hyperfunction relatively, uses antihistaminic and the coupling glucocorticoid both can increase antiinflammatory action, can prevent again and to correct histamine receptor unbalance, better efficacy.
Cough variant asthma: all use earlier prednisone and aminophyllines that is diagnosed as primary disease are treated, and then press later treating asthma, concrete grammar: oral ketotifen, suction are breathed heavily urine peace becotide spray and are treated.
Asthmatic chronic bronchitis: (1) control is infected, and uses narrow-spectrum antibiotic as far as possible, in order to avoid superinfection or generation Resistant strain; (2) eliminate the phlegm, antitussive, avoid using strong anti-tussive agents, in order to avoid inhibition maincenter and increase the weight of respiratory tract obstruction and inflammation; (3) spasmolytic, relieving asthma; (4) aerosol therapy.
Therefore, invention a kind of can better control asthma and acute and chronic bronchitis with secretions and bronchospasm, improve pulmonary function and increase the asymptomatic natural law of patient and improve patient and have great importance quality of life.
Summary of the invention
The invention provides a kind of can better control asthma and acute and chronic bronchitis with secretions and bronchospasm, improve pulmonary function and increase the asymptomatic natural law of patient and improve patient's compound ambroxol hydrochloride composition tablet of quality of life, concrete technical scheme is as follows:
A kind of compound ambroxol hydrochloride composition tablet, the effective ingredient of making in 1000 the raw material is as follows:
Preferably, the effective ingredient of making in 1000 the raw material is as follows:
Described salbutamol sulfate is in albuterol, and described hyprolose is the low hyprolose that replaces.
Compound ambroxol hydrochloride composition tablet white of the present invention or off-white color sheet.
Described ambroxol hydrochloride chemical name is the amino 3.5-dibromo-benzyl of trans-4-[(2-) amino] cyclohexanol hydrochloridumi, chemical formula is C
13H
18Br
2N
2OHCl, molecular weight are 414.6, are colourless clear liquid, and chemical structural formula is:
Described ambroxol hydrochloride is the succedaneum of Bisolvon, be to act on the strongest expectorant of relievining asthma at present clinically, the mucus that ambroxol hydrochloride can stimulate the bronchorrhea glandular secretion to be easier to flow makes the sputum dilution, toughness reduces, and can increase generation and the secretion of pulmonary surfactant, thereby reduce airway resistance, reduce the adhesive force of mucus, activate mucociliary blanket function, promote the mucociliary transhipment.Compare with the first generation and second filial generation expelling phlegm drugs, ambroxol hydrochloride is except having powerful mucolysis effect, and its maximum characteristics are that it can stimulate alveolar type II cells, promotes the synthetic and secretion of alveolar surfactant, thereby effectively strengthen mucus transport, promote expectoration.
Described salbutamol sulfate chemical name is 1-(4-hydroxyl-3-hydroxymethyl phenyl)-2-(uncle's fourth amino) ethanol sulfate, and chemical formula is (C
13H
21NO
3)
2H
2SO
4, molecular weight is 576.7, chemical structural formula is:
Described salbutamol sulfate (in albuterol) is alpha 1 beta-adrenergic
2Receptor stimulating agent can selectively acting β on bronchial smooth muscle
2Adrenoreceptor makes smooth muscle loosening in the air flue, and airway resistance reduces and can increase the mucosa cilium and removes function, suppresses mastocyte and discharges inflammatory mediators such as histamine and leukotriene, reduces vascular permeability and blood vessel and oozes out, and performance is relievingd asthma, spasmolysis.
The compound preparation that the present invention adopts ambroxol hydrochloride and albuterol to form, both synergism can be brought into play expelling phlegm for arresting cough and antasthmatic effect simultaneously, and the relieving cough symptom promotes sputum to discharge fast; The two share can better control asthma and acute and chronic bronchitis with secretions and bronchospasm; Drug combination not only improves pulmonary function, and increases the asymptomatic natural law of patient, improves patient's quality of life.
The invention also discloses a kind of preparation method of described compound ambroxol hydrochloride composition tablet, may further comprise the steps:
The first step: ambroxol hydrochloride and salbutamol sulfate are sieved respectively, standby;
Second step: hypromellose is added purified water be mixed with 3% hypromellose aqueous solution, standby;
The 3rd step: get described ambroxol hydrochloride, salbutamol sulfate, hyprolose and the lactose of recipe quantity, mix homogeneously obtains first mixture;
The 4th step: make soft material with adding the 3% hypromellose aqueous solution for preparing in the step 2 in described first mixture;
The 5th step: step 4 gained soft material is crossed 30 eye mesh screens granulate, obtain compound ambroxol hydrochloride compositions wet granular;
The 6th step: described compound ambroxol hydrochloride compositions wet granular is carried out drying through forced air drying under 55～65 ℃ of temperature, obtain the dried granule of compound ambroxol hydrochloride compositions;
The 7th step: the dried granule of described compound ambroxol hydrochloride compositions is crossed 24 eye mesh screen granulate, add polyvinylpolypyrrolidone and the magnesium stearate of recipe quantity again, mix homogeneously after quality inspection is qualified, again through tabletting, namely gets the compound ambroxol hydrochloride composition tablet.
Preferably, in the described step 1 described ambroxol hydrochloride is crossed 120 mesh sieves, described salbutamol sulfate is crossed 100 mesh sieves; Preferably, under 60 ℃ of temperature, carry out drying through blast drier in the described step 6; Preferably, described tabletting is specially: punch die dashes for the dimple form circle, and diameter is 6.5mm.
Use preparation method of the present invention, production technology is simple, and technological parameter is easy to control, is fit to suitability for industrialized production.
The specific embodiment
Describe technical scheme of the present invention below in conjunction with specific embodiments in detail, be used for explaining technical scheme of the present invention in this illustrative examples of the present invention and explanation, but not as a limitation of the invention.
A kind of compound ambroxol hydrochloride composition tablet, the effective ingredient of making in 1000 the raw material is as follows:
Described salbutamol sulfate is in albuterol, and described hyprolose is the low hyprolose that replaces.
The compound preparation that the present invention adopts ambroxol hydrochloride and albuterol to form, both synergism can be brought into play expelling phlegm for arresting cough and antasthmatic effect simultaneously, and the relieving cough symptom promotes sputum to discharge fast; The two share can better control asthma and acute and chronic bronchitis with secretions and bronchospasm; Drug combination not only improves pulmonary function, and increases the asymptomatic natural law of patient, improves patient's quality of life.
Concrete preparation method is as follows:
The first step: described ambroxol hydrochloride is crossed 120 mesh sieves, standby; Described salbutamol sulfate is crossed 100 mesh sieves, standby;
Second step: hypromellose is added purified water be mixed with 3% hypromellose aqueous solution, standby;
The 3rd step: get described ambroxol hydrochloride, salbutamol sulfate, hyprolose and the lactose of recipe quantity, mix homogeneously obtains first mixture;
The 4th step: make soft material with adding the 3% hypromellose aqueous solution for preparing in the step 2 in described first mixture;
The 5th step: step 4 gained soft material is crossed 30 eye mesh screens granulate, obtain compound ambroxol hydrochloride compositions wet granular;
The 6th step: described compound ambroxol hydrochloride compositions wet granular is carried out drying through forced air drying under 60 ℃ of temperature, obtain the dried granule of compound ambroxol hydrochloride compositions;
The 7th step: the dried granule of described compound ambroxol hydrochloride compositions is crossed 24 eye mesh screen granulate, the polyvinylpolypyrrolidone and the magnesium stearate that add recipe quantity again, mix homogeneously, after quality inspection is qualified, again through tabletting, namely get the compound ambroxol hydrochloride composition tablet, described tabletting is specially: punch die dashes for the dimple form circle, and diameter is 6.5mm.
Compound ambroxol hydrochloride composition tablet white of the present invention or off-white color sheet, stable high spot reviews project according to defined under two appendix XI of Chinese Pharmacopoeia version in 2010 X C " crude drug and pharmaceutical preparation stability test guideline " item, the respectively side of the reply ambroxol hydrochloride composition tablet samples that our company produces is carried out investigations such as character, related substance, dissolution, content, and has increased limit test of microbe latter stage in study on the stability:
Sample: compound ambroxol hydrochloride composition tablet
Lab scale sample lot number: 1019; Middle test agent lot number: 100101,100102,100103;
Source: our company's self-control.
Working standard
Ambroxol hydrochloride working standard lot number: D-M090507, content: 99.73%(is in wet product);
Salbutamol sulfate working standard lot number: D-090501, content: 99.91%(is in wet product);
Source: demarcate and get by raw material.
Influence factor's test, accelerated test, long term test have been carried out respectively.
1, influence factor's test
In order to inquire into the inherent stability of medicine, understand the factor that influence stability of drug products and may degradation pathway and catabolite, for production technology, packing, holding conditions and the analytical method of setting up catabolite provide scientific basis, carry out the influence factor and test.Get this product, test.
(1) hot test: get this product (lot number: 1019), respectively at 40 ℃ with 60 ℃ of temperature under placed 10 days,, detect result of the test and comparison in 0 day in the 5th day and sampling in the 10th day by stable high spot reviews project.Result of the test sees Table 1, table 2.
Table 1 compound ambroxol hydrochloride composition tablet influence factor result of the test 1
Table 2 compound ambroxol hydrochloride composition tablet influence factor result of the test 2
Table 3 compound ambroxol hydrochloride composition tablet moisture absorption weight increment test result
(2) high wet test
Get this product (lot number: 1019), in 25 ℃ of temperature, placed 10 days under relative humidity 90% ± 5%, 75% ± 5% the condition, in the 5th day and sampling in the 10th day, detect by stable high spot reviews project, result of the test and comparison in 0 day.Result of the test sees Table 1, table 2.(lot number: 1019), two parts, each 20, accurate title is fixed, puts respectively in relative humidity 90% ± 5%, 75% ± 5% environment and places, and in the 5th day and sampling in the 10th day, the accurate title decided, and investigated the moisture absorption weightening finish of this product to get this product.The results are shown in Table 3.
(3) exposure experiments to light
Get this product (lot number: 1019), put under the condition that intensity of illumination is 4500lx and placed 10 days, in the 5th day and sampling in the 10th day, detect by stable high spot reviews project, result of the test and comparison in 0 day.Result of the test sees Table 1, table 2.
Result of the test shows: this product was placed 5 days under relative humidity 90% ± 5% condition, and moisture absorption is increased weight greater than 5.0%, so no longer other every indexs are checked, only the every index under relative humidity 75% condition was checked.This product was placed 10 days under illumination, high temperature, super-humid conditions, and under illumination, 60 ℃ of conditions of high temperature, outside the related substance of ambroxol hydrochloride and salbutamol sulfate slightly increased, every index was compared with 0 day under other each conditions all significant change; With reference to above result of the test, and in conjunction with ambroxol hydrochloride sheet and salbutamol sulfate sheet Chinese Pharmacopoeia version two ministerial standards in 2010, the holding conditions of this product is decided to be: shading, sealing preservation.
2, study on the stability
(1) accelerated test: get each batch sample of pilot scale, the simulation commercially available back is that 40 ± 2 ℃, relative humidity are to place 6 months under 75% ± 5% the condition in temperature, respectively at the 1st, 2,3,6 sampling at the end of month once, measures by stable high spot reviews project.Result of the test sees Table 4, table 5.
Table 4 compound ambroxol hydrochloride composition tablet accelerated test result 1
Table 5 compound ambroxol hydrochloride composition tablet accelerated test result 2
By the accelerated test result as can be known, this product was investigated through accelerated test in 6 months, and outside the related substance of demineralizing acid ambroxol and salbutamol sulfate slightly increased, other every indexs did not have significant change, all in prescribed limit.Show this product by above-mentioned packing, basicly stable under the condition of 40 ℃ ± 2 ℃ of temperature, relative humidity 75% ± 5%.
Table 6 compound ambroxol hydrochloride composition tablet long-term test results 1
Table 7 compound ambroxol hydrochloride composition tablet long-term test results 2
(2) long term test
Get each batch sample of pilot scale, the simulation commercially available back is that 25 ℃ ± 2 ℃, relative humidity are to place under 60% ± 10% condition in temperature, respectively at the 3rd, 6,9,12,18,24,36 sampling at the end of month once, measure by stable high spot reviews project, result of the test sees Table 6, table 7.
By long-term test results as can be known, this product was investigated through long term test in 12 months, and outside the related substance of demineralizing acid ambroxol and salbutamol sulfate slightly increased, significant change did not take place other every indexs, all in prescribed limit.Show this product by above-mentioned packing, basicly stable under the condition of 25 ℃ ± 2 ℃ of temperature, relative humidity 60% ± 10%.This test is not finished as yet, well afoot.
In sum, with reference to above influence factor's result of the test, and in conjunction with ambroxol hydrochloride sheet and salbutamol sulfate sheet Chinese Pharmacopoeia version two ministerial standards in 2010, the holding conditions of this product is decided to be: shading, sealing preservation.Stability test according to each batch sample is investigated the result, and it is 18 months that the effect duration of this product is fixed tentatively.
With reference to ambroxol hydrochloride and ambroxol hydrochloride sheet standard (Chinese Pharmacopoeia 2005 and 2010 version two ones), salbutamol sulfate and salbutamol sulfate sheet standard (Chinese Pharmacopoeia 2005 and 2010 version two ones), salbutamol sulfate standard (BP2009), and according to quality research result of the test and stability test result, work out this standard.
1, nomenclature of drug
According to " Chinese adopted drug name nomenclature principle ", and with reference to two ones of Chinese Pharmacopoeia versions in 2010
Relevant kind and formulating.
2, content limit
With reference to ambroxol hydrochloride sheet standard (Chinese Pharmacopoeia 2010 version two ones), salbutamol sulfate sheet standard (Chinese Pharmacopoeia 2010 version two ones), and according to the result of the test of each batch sample assay of quality research and the result of stability test, the specification of considering this product simultaneously is less, determines that this product limit is: this product ambroxol-hydrochloride-containing (C
13H
18Br
2N
2OHCl) press albuterol (C with salbutamol sulfate
13H
21NO
3) calculate and all should be 90.0%～110.0% of labelled amount.
3, character
According to the character check result of each batch sample of this product, and in conjunction with the appearance character of raw material and adjuvant, determine that the character of this product is: this product is white or off-white color sheet.Order into quality standard.
4, differentiate
With reference to salbutamol sulfate sheet standard (Chinese Pharmacopoeia 2010 version two ones) and ambroxol hydrochloride sheet standard (Chinese Pharmacopoeia 2010 version two ones), and in conjunction with the result of the test of each batch sample, will differentiate that a design is as follows:
(1) get 5 of this product, porphyrize adds water 5ml, and jolting makes the salbutamol sulfate dissolving, filters, and filtrate adds 1 of ferric chloride test solution, jolting, and solution shows purple; Add the sodium bicarbonate test solution and namely generate orange-yellow muddiness.Each batch sample and salbutamol sulfate working standard are operated with method, all are positive reaction, and blank adjuvant and ambroxol hydrochloride working standard are negative response.
(2) get 5 of this product, porphyrize adds 0.4% borax soln 20ml jolting and makes dissolving, filters, and adds 3%4-amino-antipyrine solution 1ml and 2% potassium ferricyanide solution 1ml, adds chloroform 10ml jolting, places and makes layering, and it is orange red that the chloroform layer shows.Each batch sample and salbutamol sulfate working standard are operated with method, all are positive reaction, and blank adjuvant and ambroxol hydrochloride working standard are negative response.
(3) in the chromatogram that records under ambroxol hydrochloride and salbutamol sulfate assay item, the retention time of the need testing solution main peak all retention time with the reference substance solution main peak is consistent.It is ordered into quality standard.
5, check
(1) related substance
Ambroxol hydrochloride is formulated with reference to ambroxol hydrochloride and ambroxol hydrochloride sheet standard (Chinese Pharmacopoeia 2010 version two ones).Methodology evidence by systems such as system suitability test, blank interference test, destructive testing, linear relationship test, precision test and minimum detectable activities, this chromatographic condition is applicable to the inspection of ambroxol hydrochloride related substance in this product, salbutamol sulfate and blank adjuvant are noiseless, can satisfy the requirement that stability test is investigated.In the time of 6 months, carried out the comparative study of self-control sample and ambroxol hydrochloride sheet listing sample impurity in accelerated test.The result shows, the kind basically identical of the impurity that exists among the kind of the impurity that exists among the self-control sample chromatogram figure and the listing sample chromatogram figure makes namely that impurities is consistent with the sample impurities that goes on the market in the sample by oneself.
Salbutamol sulfate is formulated with reference to salbutamol sulfate standard (BP2009).Methodology evidence by systems such as system suitability test, blank interference test, destructive testing, linear relationship test, precision test and minimum detectable activities, this chromatographic condition is applicable to the inspection of salbutamol sulfate related substance in this product, ambroxol hydrochloride and blank adjuvant are noiseless, can satisfy the requirement that stability test is investigated.In the time of 12 months, carried out the comparative study of self-control sample and salbutamol sulfate sheet listing sample impurity in long term test.The result shows, the kind basically identical of the impurity that exists among the kind of the impurity that exists among the self-control sample chromatogram figure and the listing sample chromatogram figure, and, make namely that impurities is consistent with the sample impurities that goes on the market in the sample by oneself.
(2) uniformity of dosage units
Because of every ambroxol-hydrochloride-containing 7.5mg of this product, salbutamol sulfate 2.4mg(is equivalent to albuterol 2mg), should check uniformity of dosage units.Because this product adopts the content of high effective liquid chromatography for measuring ambroxol hydrochloride and salbutamol sulfate, so still adopt high performance liquid chromatography to check the uniformity of dosage units of this product.Each batch sample is operated with method, and the result is all up to specification.Order into quality standard.
(3) dissolution
Easily molten in water because of salbutamol sulfate, ambroxol hydrochloride is slightly molten in water, so be dissolution medium with water.Because of every ambroxol-hydrochloride-containing 7.5mg of this product, salbutamol sulfate 2.4mg(is equivalent to albuterol 2mg), so determine that the volume of dissolution medium is 200ml.UV scanning figure by relatively ambroxol hydrochloride and salbutamol sulfate as can be known, as adopt ultraviolet visible spectrophotometry to measure the stripping quantity of two principal agents, the mutual interference of two principal agents meeting phase, therefore select for use the HPLC method respectively the stripping quantity of ambroxol hydrochloride sulfur and sour albuterol to be measured, chromatographic condition is with under the assay item.By the methodology evidence of system, the linearity of this product dissolution method, precision, the response rate, stability of solution are all good, are fit to the dissolution test of this product; In addition filter membrane absorption is investigated, the result shows that 0.45 μ m filter membrane adsorption rate less than 2%, do not disturb the dissolution determination of this product substantially; According to the dissolution determination result of each batch sample of this product, the stripping limit of ambroxol hydrochloride in this product and albuterol all is decided to be 80% of labelled amount.It is ordered into quality standard.
(4) other
According to stipulating under two appendix I of Chinese Pharmacopoeia version in 2010 A tablet general rule item, should check microbial limit, each batch sample is through check, and is all up to specification.Order into quality standard.
6, assay
Ambroxol hydrochloride adopts the content of ambroxol hydrochloride in high effective liquid chromatography for measuring this product with reference to ambroxol hydrochloride and ambroxol hydrochloride sheet standard (Chinese Pharmacopoeia 2010 version two ones).By the methodology evidence of system, linearity, the precision of this method are good, and the stability of solution and the response rate are all good, are fit to the assay of this product.Order into quality standard.
Salbutamol sulfate adopts the content of salbutamol sulfate in high effective liquid chromatography for measuring this product with reference to salbutamol sulfate sheet standard (Chinese Pharmacopoeia 2005 and 2010 version two ones).By the methodology evidence of system, linearity, the precision of this method are good, and the stability of solution and the response rate are all good, are fit to the assay of this product.Order into quality standard.
7, classification
With reference to ambroxol hydrochloride standard (Chinese Pharmacopoeia 2010 version two ones), salbutamol sulfate standard (Chinese Pharmacopoeia 2010 version two ones) is formulated.
8, storage
With reference to ambroxol hydrochloride and ambroxol hydrochloride sheet standard (Chinese Pharmacopoeia 2010 version two ones), salbutamol sulfate and salbutamol sulfate sheet standard (Chinese Pharmacopoeia 2010 version two ones), and the combination stability result of the test is formulated.
The above is preferred implementation of the present invention; should be pointed out that for those skilled in the art, under the prerequisite that does not break away from the principle of the invention; can also make some improvements and modifications, these improvements and modifications also are considered as protection scope of the present invention.
Claims (6)
1. compound ambroxol hydrochloride composition tablet, it is characterized in that: the effective ingredient of making 1000 is as follows:
Ambroxol hydrochloride 7.0-8.0g
Salbutamol sulfate 1.5-2.5g
Lactose 70-80g
Hyprolose 15-25g
3% hypromellose aqueous solution is an amount of
Polyvinylpolypyrrolidone 5-8g
Magnesium stearate 0.5-1.5g.
2. compound ambroxol hydrochloride composition tablet according to claim 1, it is characterized in that: the effective ingredient of making 1000 is as follows:
Ambroxol hydrochloride 7.5g
Salbutamol sulfate 2g
Lactose 75g
Hyprolose 20g
3% hypromellose aqueous solution is an amount of
Polyvinylpolypyrrolidone 6g
Magnesium stearate 1g.
3. method for preparing as compound ambroxol hydrochloride composition tablet as described in claim 1 or 2 is characterized in that: may further comprise the steps:
(1) ambroxol hydrochloride and salbutamol sulfate are sieved respectively, standby;
(2) hypromellose is added purified water and be mixed with 3% hypromellose aqueous solution, standby;
(3) get described ambroxol hydrochloride, salbutamol sulfate, hyprolose and the lactose of recipe quantity, mix homogeneously obtains first mixture;
(4) make soft material with adding the 3% hypromellose aqueous solution for preparing in the step (2) in described first mixture;
(5) step (4) gained soft material is crossed 30 eye mesh screens and granulated, obtain compound ambroxol hydrochloride compositions wet granular;
(6) described compound ambroxol hydrochloride compositions wet granular is carried out drying through forced air drying under 55～65 ℃ of temperature, obtain the dried granule of compound ambroxol hydrochloride compositions;
(7) the dried granule of described compound ambroxol hydrochloride compositions is crossed 24 eye mesh screen granulate, add polyvinylpolypyrrolidone and the magnesium stearate of recipe quantity again, mix homogeneously after quality inspection is qualified, again through tabletting, namely gets the compound ambroxol hydrochloride composition tablet.
4. the method for preparing the compound ambroxol hydrochloride composition tablet according to claim 3, it is characterized in that: described step is crossed 120 mesh sieves with described ambroxol hydrochloride in (1), and described salbutamol sulfate is crossed 100 mesh sieves.
5. the method for preparing the compound ambroxol hydrochloride composition tablet according to claim 3 is characterized in that: carry out drying through blast drier under 60 ℃ of temperature in the described step (6).
6. the method for preparing the compound ambroxol hydrochloride composition tablet according to claim 3, it is characterized in that: the tabletting in the described step (7) is specially: punch die dashes for the dimple form circle, and diameter is 6.5mm.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN105326815A (en) * | 2015-12-08 | 2016-02-17 | 青岛正大海尔制药有限公司 | Preparation method of controlled release capsules containing ambroxol hydrochloride and salbutamol sulfate |
| CN105326796A (en) * | 2015-12-08 | 2016-02-17 | 青岛正大海尔制药有限公司 | Powder containing ambroxol hydrochloride and salbutamol sulfate |
| CN105395500A (en) * | 2015-12-07 | 2016-03-16 | 青岛正大海尔制药有限公司 | Preparation method of ambroxol-salbutamol tablet |
| CN105412055A (en) * | 2015-12-07 | 2016-03-23 | 青岛正大海尔制药有限公司 | Ambroxol and salbutamol tablet |
| CN105434412A (en) * | 2015-12-08 | 2016-03-30 | 青岛正大海尔制药有限公司 | Ambroxol and salbutamol controlled release capsule |
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|---|---|---|---|---|
| CN101099729A (en) * | 2006-07-03 | 2008-01-09 | 天津康鸿医药科技发展有限公司 | Oral solid preparation containing ambroxol hydrochloride and salbutamol active components |
| CN102240276A (en) * | 2011-04-27 | 2011-11-16 | 陕西合成药业有限公司 | Granular preparation containing ambroxolhydrochloride and salbutamol sulfate and preparation method thereof |
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2013
- 2013-05-08 CN CN201310166801.0A patent/CN103251577B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101099729A (en) * | 2006-07-03 | 2008-01-09 | 天津康鸿医药科技发展有限公司 | Oral solid preparation containing ambroxol hydrochloride and salbutamol active components |
| CN102240276A (en) * | 2011-04-27 | 2011-11-16 | 陕西合成药业有限公司 | Granular preparation containing ambroxolhydrochloride and salbutamol sulfate and preparation method thereof |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105395500A (en) * | 2015-12-07 | 2016-03-16 | 青岛正大海尔制药有限公司 | Preparation method of ambroxol-salbutamol tablet |
| CN105412055A (en) * | 2015-12-07 | 2016-03-23 | 青岛正大海尔制药有限公司 | Ambroxol and salbutamol tablet |
| CN105326815A (en) * | 2015-12-08 | 2016-02-17 | 青岛正大海尔制药有限公司 | Preparation method of controlled release capsules containing ambroxol hydrochloride and salbutamol sulfate |
| CN105326796A (en) * | 2015-12-08 | 2016-02-17 | 青岛正大海尔制药有限公司 | Powder containing ambroxol hydrochloride and salbutamol sulfate |
| CN105434412A (en) * | 2015-12-08 | 2016-03-30 | 青岛正大海尔制药有限公司 | Ambroxol and salbutamol controlled release capsule |
| CN105326815B (en) * | 2015-12-08 | 2018-06-01 | 青岛正大海尔制药有限公司 | The preparation method of ambroxol salbutamol controlled release capsule |
| CN105326796B (en) * | 2015-12-08 | 2018-06-05 | 青岛正大海尔制药有限公司 | Ambroxol salbutamol powder |
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| Publication number | Publication date |
|---|---|
| CN103251577B (en) | 2015-04-22 |
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