CN104940155A - Ambroxol hydrochloride composition tablet as medicine for treating respiratory disease - Google Patents
Ambroxol hydrochloride composition tablet as medicine for treating respiratory disease Download PDFInfo
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- CN104940155A CN104940155A CN201510467710.XA CN201510467710A CN104940155A CN 104940155 A CN104940155 A CN 104940155A CN 201510467710 A CN201510467710 A CN 201510467710A CN 104940155 A CN104940155 A CN 104940155A
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- ambroxol hydrochloride
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- ambroxol
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Abstract
The invention discloses an ambroxol hydrochloride composition tablet as medicine for treating respiratory disease and belongs to the technical field of medicines. The composition is composed of ambroxol hydrochloride, sodium carboxymethyl starch, sodium chloride, lactose F100, microcrystalline cellulose 102, and superfine silica powder. The ambroxol hydrochloride is classified as a novel crystal form composite, an x-ray powder diffraction pattern measured by using Cu-K alpha rays is as shown in Figure 1, the ambroxol hydrochloride is different from the ambroxol hydrochloride reported in the prior art, test results show that the ambroxol hydrochloride composition is better in solubleness and higher in stability, the preparation of all preparations is facilitated, the preparation method of the ambroxol hydrochloride crystal form composition tablet is simple, the stability is good, and the dissolution rate is high.
Description
Technical field
The invention belongs to medical art, relate to a kind of medicine ambroxol hydrochloride composition tablet for the treatment of respiratory system disease.
Background technology
Ambroxol hydrochloride (Ambroxol Hydrochloride) has another name called Ambroxol Hydrochloride, a kind of respiratory tract lubrication expectorant and mucolytic, ambroxol hydrochloride, chemical name is trans-4-[(2-amino-3,5-dibromo-benzyl) amino] cyclohexanol HCI, for white is to micro-yellow crystalline powder; Ambroxol hydrochloride has the characteristic that mucus is got rid of facilitation and dissolved secretions, and it can promote the eliminating of thick secretions in respiratory tract and reduce the delay of mucus, thus significantly promotes expectoration, improves breath state.The secretion of pulmonary surfactant, the secretion of air flue liquid and ciliary movement can be promoted.Ambroxol hydrochloride is widely used in the thick sputum, dys-expectoration etc. that various acute and chronic respiratory tract disease causes clinically.
At present, the polymorphic about ambroxol hydrochloride has disclosed a lot of patent and document.
The pharmaceutical composition that patent ZL201210513123.6 discloses a kind of ambroxol hydrochloride crystal formation and obtained by this crystal formation, described ambroxol hydrochloride crystal formation in the X-ray powder diffraction pattern represented with the 2 θ ± 0.2 ° angle of diffraction at 6.9 °, 7.2 °, 12.8 °, 15.6 °, 17.5 °, 20 °, 21 °, 22 °, 24 ° of places demonstrate characteristic diffraction peak.
Patent ZL201210231927.7 relates to a kind of unformed ambroxol compound and preparation method thereof, and the X-ray powder diffraction pattern of this unformed powder is without obvious characteristic peak.
Patent application 201410071920.2 relates to a kind of ambroxol compound and oral cavity disintegration tablet.The X-ray powder diffraction pattern that ambroxol hydrochloride of the present invention uses the measurement of Cu-K alpha ray to obtain as shown in Figure 1.Containing ambroxol hydrochloride 10-30 weight portion, filler 50-80 weight portion, disintegrating agent 10-15 weight portion, fluidizer 0.3-1.6 weight portion, lubricant 0.4-1.6 weight portion, correctives 8-16 weight portion in Orally disintegrating tablet of ambroxol hydrochloride.
Ambroxol hydrochloride is insoluble in water, very large difficulty is brought to the preparation of preparation, the present invention proposes a kind of new hydrochloric acid ammonia bromine compounds, there is good dissolubility and higher stability, facilitate the preparation of various preparation, utilize and the invention provides that the method for preparing tablet thereof that ambroxol hydrochloride crystal-form compound makes is simple, good stability, dissolution are high.
Summary of the invention
Goal of the invention of the present invention is to provide a kind of medicine ambroxol hydrochloride composition tablet for the treatment of respiratory system disease.
In order to complete object of the present invention, the technical scheme of employing is:
Treat a medicine ambroxol hydrochloride composition tablet for respiratory system disease, described compositions is made up of ambroxol hydrochloride, sodium starch glycolate, sodium chloride, lactose F100, microcrystalline Cellulose 102, micropowder silica gel; Described ambroxol hydrochloride is crystal, and the X-ray powder diffraction pattern that the measurement of use Cu-K alpha ray obtains as shown in Figure 1.
Preferably, with parts by weight, described compositions is made up of the ambroxol hydrochloride of 2 weight portions, the sodium starch glycolate of 2.00-2.06 weight portion, the sodium chloride of 0.50-0.58 weight portion, the microcrystalline Cellulose 102 of lactose F100,7.7-8.1 weight portion of 3.60-3.70 weight portion, the micropowder silica gel of 0.4-0.6 weight portion.
Preferably, with parts by weight, described compositions is made up of the micropowder silica gel of the sodium chloride of the sodium starch glycolate of the ambroxol hydrochloride of 2 weight portions, 2.03 weight portions, 0.54 weight portion, the lactose F100 of 3.65 weight portions, microcrystalline Cellulose 102,0.5 weight portion of 7.9 weight portions.
The preparation method of described compositions comprises the following steps:
1) supplementary material process: raw material ambroxol hydrochloride to be sieved 80 orders with oscillating sieving machine;
2) weigh: weigh according to technology preparation;
3) always mix: the ambroxol hydrochloride of recipe quantity, sodium starch glycolate, sodium chloride, lactose F100, microcrystalline Cellulose 102 are placed in three-dimensional motion mixer, motor rotation frequency 200r/min is set, open mixer and mix 15 minutes, the micropowder silica gel of recipe quantity is added after having mixed, motor rotation frequency 200r/min is set, opens mixer and mix 5 minutes;
4) tabletting: select high speed tablet press tabletting, regulate pressure to make the molding of slice, thin piece energy and hardness at 4-8kgf;
5) pack.
The preparation method of the crystal of described ambroxol hydrochloride comprises the following steps:
Be dissolved in by ambroxol hydrochloride in the mixed solvent of methanol that 35 DEG C of volumes are 6 times of ambroxol hydrochloride weight, dimethyl sulfoxine, the volume ratio of methanol and dimethyl sulfoxine is 4:1.5; First add with the speed of 25ml/min the ethanol of 9 times and the mixed solvent of ether that volume is ambroxol hydrochloride weight, the volume ratio of ethanol, ether is 2.5:1, and limit edged stirs, control temperature 35 DEG C, growing the grain 2 hours; And then the distilled water of 7 times that volume total amount is ambroxol hydrochloride weight is added with the speed of 20ml/min, growing the grain, after 1 hour, is cooled to-5 DEG C with the speed of 10 DEG C/h, then keeps mixing speed 90 revs/min of stirring and crystallizing, growing the grain 2 hours; Filter, washing, drying under reduced pressure obtains ambroxol hydrochloride crystalline compounds.
Below technical scheme of the present invention is made further explanation:
The present invention is by the precise controlling to crystallization condition, and prepared a kind of ambroxol hydrochloride novel crystal forms unlike the prior art, the X-ray powder diffraction pattern of this ambroxol hydrochloride crystal unlike the prior art.Simultaneously due to the ins and outs of this crystal formation, find through test, ambroxol compound of the present invention has good dissolubility and higher stability, facilitate the preparation of various preparation, utilize and the invention provides that the method for preparing tablet thereof that ambroxol hydrochloride crystal-form compound makes is simple, good stability, dissolution are high.
Accompanying drawing explanation
Fig. 1 is the X-ray powder diffraction that the ambroxol hydrochloride crystal of the embodiment of the present invention 1 preparation uses the measurement of Cu-K alpha ray to obtain.
Detailed description of the invention
Below by specific embodiment, summary of the invention of the present invention is described in further detail, but does not therefore limit content of the present invention.
embodiment 1:the preparation of ambroxol hydrochloride crystal
Be dissolved in by ambroxol hydrochloride in the mixed solvent of methanol that 35 DEG C of volumes are 6 times of ambroxol hydrochloride weight, dimethyl sulfoxine, the volume ratio of methanol and dimethyl sulfoxine is 4:1.5; First add with the speed of 25ml/min the ethanol of 9 times and the mixed solvent of ether that volume is ambroxol hydrochloride weight, the volume ratio of ethanol, ether is 2.5:1, and limit edged stirs, control temperature 35 DEG C, growing the grain 2 hours; And then the distilled water of 7 times that volume total amount is ambroxol hydrochloride weight is added with the speed of 20ml/min, growing the grain, after 1 hour, is cooled to-5 DEG C with the speed of 10 DEG C/h, then keeps mixing speed 90 revs/min of stirring and crystallizing, growing the grain 2 hours; Filter, washing, drying under reduced pressure obtains ambroxol hydrochloride crystalline compounds.
As shown in Figure 1, its purity of high-performance liquid chromatogram determination is 99.9% to the X-ray powder diffraction pattern that the ambroxol hydrochloride crystal prepared uses the measurement of Cu-K alpha ray to obtain.
embodiment 2:the preparation of Ambroxol Hydrochloride Tablets
Prescription: with parts by weight as table 1
Table 1 ambroxol hydrochloride composition prescription
Preparation method:
1) supplementary material process: raw material ambroxol hydrochloride to be sieved 80 orders with oscillating sieving machine;
2) weigh: weigh according to technology preparation;
3) always mix: the ambroxol hydrochloride of recipe quantity, sodium starch glycolate, sodium chloride, lactose F100, microcrystalline Cellulose 102 are placed in three-dimensional motion mixer, motor rotation frequency 200r/min is set, open mixer and mix 15 minutes, the micropowder silica gel of recipe quantity is added after having mixed, motor rotation frequency 200r/min is set, opens mixer and mix 5 minutes;
4) tabletting: select high speed tablet press tabletting, regulate pressure to make the molding of slice, thin piece energy and hardness at 4-8kgf;
5) pack.
embodiment 3:the preparation of Ambroxol Hydrochloride Tablets
Prescription: with parts by weight as table 2
Table 2 ambroxol hydrochloride composition prescription
Preparation method:
1) supplementary material process: raw material ambroxol hydrochloride to be sieved 80 orders with oscillating sieving machine;
2) weigh: weigh according to technology preparation;
3) always mix: the ambroxol hydrochloride of recipe quantity, sodium starch glycolate, sodium chloride, lactose F100, microcrystalline Cellulose 102 are placed in three-dimensional motion mixer, motor rotation frequency 200r/min is set, open mixer and mix 15 minutes, the micropowder silica gel of recipe quantity is added after having mixed, motor rotation frequency 200r/min is set, opens mixer and mix 5 minutes;
4) tabletting: select high speed tablet press tabletting, regulate pressure to make the molding of slice, thin piece energy and hardness at 4-8kgf;
5) pack.
embodiment 4:the preparation of Ambroxol Hydrochloride Tablets
Prescription: with parts by weight as table 3
Table 3 ambroxol hydrochloride composition prescription
Preparation method:
1) supplementary material process: raw material ambroxol hydrochloride to be sieved 80 orders with oscillating sieving machine;
2) weigh: weigh according to technology preparation;
3) always mix: the ambroxol hydrochloride of recipe quantity, sodium starch glycolate, sodium chloride, lactose F100, microcrystalline Cellulose 102 are placed in three-dimensional motion mixer, motor rotation frequency 200r/min is set, open mixer and mix 15 minutes, the micropowder silica gel of recipe quantity is added after having mixed, motor rotation frequency 200r/min is set, opens mixer and mix 5 minutes;
4) tabletting: select high speed tablet press tabletting, regulate pressure to make the molding of slice, thin piece energy and hardness at 4-8kgf;
5) pack.
experimental example 1:mobility is tested
The mobility of this experimental example to the ambroxol compound of the embodiment of the present invention 1 detects, adopt fixed funnel method, funnel is placed in the suitable height on graph paper, ambroxol compound is freely flowed down from bell mouth, until the cone top formed contacts with bell mouth, measure hypotenuse and the horizontal angle (θ angle of repose) of ambroxol compound accumulation horizon.Experimental result is as shown in table 4.
Table 4 mobility experimental result
From the interpretation of table 4, the mobility of the ambroxol compound that the embodiment of the present invention 1 prepares is fine.
experimental example 2:dissolubility contrast test
the dissolubility of following ambroxol hydrochloride is detected,
Comparative example 1: commercially available ambroxol hydrochloride (Wuhan English and pharmaceutical Co. Ltd);
Comparative example 2: prepare according to the embodiment 1 of patent ZL201210513123.6;
Comparative example 3: prepare according to the embodiment 1 of patent ZL201210231927.7;
Comparative example 4: prepare according to the embodiment 1 of patent application 201410071920.2;
1. be determined at the quality of ambroxol hydrochloride in 100g water saturation solution under 20 DEG C of conditions; Experimental result is as shown in table 5.
Table 5 dissolubility comparative test result
As can be seen from Table 5, the water solublity of ambroxol hydrochloride of the present invention improves greatly, brings conveniently to preparation preparation.
experimental example 3:influence factor tests
1. hot test
The tablet that Example 2 prepares, simulation listing packaging, puts in sealing clean container, places 10 days at 40 ± 2 DEG C of temperature, and in the 5th day and sampling in the 10th day, detect by stability high spot reviews project, result of the test compared with 0 day.
2. high humility test
The tablet that Example 2 prepares, simulation listing packaging, puts in sealing clean container, place 10 days under the condition of 25 ± 2 DEG C of relative humiditys 90% ± 5%, in the 5th day and sampling in the 10th day, detect by stability high spot reviews project, result of the test compared with 0 day.
3. strong illumination test
The tablet that Example 2 prepares, simulation listing packaging, puts in sealing clean container, and being placed in illumination is place 10 days under the condition of 4500lx, and in the 5th day and sampling in the 10th day, detect by stability high spot reviews project, result compared with 0 day.The results are shown in Table 6:
Table 6 influence factor result of the test
Result shows: the ambroxol hydrochloride tablet that the present invention prepares, its good stability, and dissolution is high, and under high temperature, high humidity, high light conditions, equal retention is stablized.Influence factor's experiment is carried out to the ambroxol hydrochloride tablet that other embodiments of the invention prepare, obtains identical experimental result.
Claims (5)
1. treat a medicine ambroxol hydrochloride composition tablet for respiratory system disease, it is characterized in that: described compositions is made up of ambroxol hydrochloride, sodium starch glycolate, sodium chloride, lactose F100, microcrystalline Cellulose 102, micropowder silica gel; Described ambroxol hydrochloride is crystal, and the X-ray powder diffraction pattern that the measurement of use Cu-K alpha ray obtains as shown in Figure 1.
2. the medicine ambroxol hydrochloride composition tablet for the treatment of respiratory system disease according to claim 1, it is characterized in that: with parts by weight, described compositions is made up of the ambroxol hydrochloride of 2 weight portions, the sodium starch glycolate of 2.00-2.06 weight portion, the sodium chloride of 0.50-0.58 weight portion, the microcrystalline Cellulose 102 of lactose F100,7.7-8.1 weight portion of 3.60-3.70 weight portion, the micropowder silica gel of 0.4-0.6 weight portion.
3. the medicine ambroxol hydrochloride composition tablet for the treatment of respiratory system disease according to claim 1, it is characterized in that: with parts by weight, described compositions is made up of the micropowder silica gel of the sodium chloride of the sodium starch glycolate of the ambroxol hydrochloride of 2 weight portions, 2.03 weight portions, 0.54 weight portion, the lactose F100 of 3.65 weight portions, microcrystalline Cellulose 102,0.5 weight portion of 7.9 weight portions.
4., according to the medicine ambroxol hydrochloride composition tablet of the arbitrary described treatment respiratory system disease of claim 1-3, it is characterized in that, the preparation method of described composition tablet comprises the following steps:
1) supplementary material process: raw material ambroxol hydrochloride to be sieved 80 orders with oscillating sieving machine;
2) weigh: weigh according to technology preparation;
3) always mix: the ambroxol hydrochloride of recipe quantity, sodium starch glycolate, sodium chloride, lactose F100, microcrystalline Cellulose 102 are placed in three-dimensional motion mixer, motor rotation frequency 200r/min is set, open mixer and mix 15 minutes, the micropowder silica gel of recipe quantity is added after having mixed, motor rotation frequency 200r/min is set, opens mixer and mix 5 minutes;
4) tabletting: select high speed tablet press tabletting, regulate pressure to make the molding of slice, thin piece energy and hardness at 4-8kgf;
5) pack.
5. the medicine ambroxol hydrochloride composition tablet for the treatment of respiratory system disease according to claim 1, is characterized in that, the preparation method of described ambroxol hydrochloride crystal comprises the following steps:
Be dissolved in by ambroxol hydrochloride in the mixed solvent of methanol that 35 DEG C of volumes are 6 times of ambroxol hydrochloride weight, dimethyl sulfoxine, the volume ratio of methanol and dimethyl sulfoxine is 4:1.5; First add with the speed of 25ml/min the ethanol of 9 times and the mixed solvent of ether that volume is ambroxol hydrochloride weight, the volume ratio of ethanol, ether is 2.5:1, and limit edged stirs, control temperature 35 DEG C, growing the grain 2 hours; And then the distilled water of 7 times that volume total amount is ambroxol hydrochloride weight is added with the speed of 20ml/min, growing the grain, after 1 hour, is cooled to-5 DEG C with the speed of 10 DEG C/h, then keeps mixing speed 90 revs/min of stirring and crystallizing, growing the grain 2 hours; Filter, washing, drying under reduced pressure obtains ambroxol hydrochloride crystalline compounds.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510467710.XA CN104940155A (en) | 2015-08-04 | 2015-08-04 | Ambroxol hydrochloride composition tablet as medicine for treating respiratory disease |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201510467710.XA CN104940155A (en) | 2015-08-04 | 2015-08-04 | Ambroxol hydrochloride composition tablet as medicine for treating respiratory disease |
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| CN201510467710.XA Withdrawn CN104940155A (en) | 2015-08-04 | 2015-08-04 | Ambroxol hydrochloride composition tablet as medicine for treating respiratory disease |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030171391A1 (en) * | 2002-01-25 | 2003-09-11 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Ambroxol for the treatment of chronic pain |
| CN102964257A (en) * | 2012-11-24 | 2013-03-13 | 沈阳新马药业有限公司 | Ambroxol hydrochloride compound and medicine composition thereof |
| JP2013147494A (en) * | 2011-12-20 | 2013-08-01 | Daiichi Sankyo Healthcare Co Ltd | Safe internal medicine composition |
| CN104788327A (en) * | 2015-05-15 | 2015-07-22 | 苗怡文 | Ambroxol hydrochloride compound for treating respiratory system disease and preparation method of ambroxol hydrochloride compound |
-
2015
- 2015-08-04 CN CN201510467710.XA patent/CN104940155A/en not_active Withdrawn
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030171391A1 (en) * | 2002-01-25 | 2003-09-11 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Ambroxol for the treatment of chronic pain |
| JP2013147494A (en) * | 2011-12-20 | 2013-08-01 | Daiichi Sankyo Healthcare Co Ltd | Safe internal medicine composition |
| CN102964257A (en) * | 2012-11-24 | 2013-03-13 | 沈阳新马药业有限公司 | Ambroxol hydrochloride compound and medicine composition thereof |
| CN104788327A (en) * | 2015-05-15 | 2015-07-22 | 苗怡文 | Ambroxol hydrochloride compound for treating respiratory system disease and preparation method of ambroxol hydrochloride compound |
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Application publication date: 20150930 |
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