CN103565753B - Ambroxol Hydrochloride Granules and preparation method thereof - Google Patents
Ambroxol Hydrochloride Granules and preparation method thereof Download PDFInfo
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- CN103565753B CN103565753B CN201310491704.9A CN201310491704A CN103565753B CN 103565753 B CN103565753 B CN 103565753B CN 201310491704 A CN201310491704 A CN 201310491704A CN 103565753 B CN103565753 B CN 103565753B
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Abstract
The invention discloses a kind of Ambroxol Hydrochloride Granules, be made up of the component of following weight portion: 20 ~ 50 parts of ambroxol hydrochlorides, 500 ~ 1000 portions of mannitol, 10 ~ 50 parts of correctivess, 1 ~ 5 part of binding agent, described binding agent is that the hypromellose of 1:0.5 ~ 1 and No. II, acrylic resin form by mass ratio.Ambroxol Hydrochloride Granules of the present invention is granulated with microencapsulation, can reduce poisonous side effect of medicine, covers bad smell and taste, improves the stability of medicine in the intestines and stomach or the zest reduced stomach.By the screening of adjuvant, can not only wall sticking phenomenon be avoided, improve the quality standard of obtained ambroxol hydrochloride, also reduce the hygroscopic effect in storage process.The invention also discloses the preparation method of this Ambroxol Hydrochloride Granules, this preparation method is simple, and drying time is short, with short production cycle, and without the need to any special installation, cost is low, is suitable for suitability for industrialized production.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, be specifically related to a kind of Ambroxol Hydrochloride Granules and preparation method thereof.
Background technology
Up to now, research report both at home and abroad about ambroxol hydrochloride is more, and phase early 1980s, ambroxol hydrochloride is declared at first by German Boehringer Ingelheim company and gone on the market, its formal name used at school is ambroxol hydrochloride (Ambroxol HCl), trade name mucosolvan (Mucosolvan).Went on the market successively in multiple countries such as France, Italy, Japan, Spain afterwards, domestic also have the ambroxol hydrochloride of different dosage form to go on the market in succession.Up to the present, the ambroxol hydrochloride dosage form of having gone on the market has tablet, granule, capsule, slow releasing capsule, slow-release pill, syrup, oral liquid, chewable tablet, oral cavity disintegration tablet, effervescent tablet and injection etc.
The patent No. is disclose a kind of Ambroxol Hydrochloride Granules and production technology thereof in the Chinese invention patent application of CN1628647A, and the method adopts a large amount of sucrose to granulate, and pelletization is sticky wall easily, and storage ability is poor.
The patent No. is disclose the stable Pharmaceutical composition of a kind of ambroxol hydrochloride granula in the Chinese invention patent application of CN1836654A, wherein with the addition of aspartame adjuvant, and aspartame is heated to 30 degrees Celsius, capital causes the Toxic producing methanol, and a large amount of long-term taking can cause the untoward reaction such as stomachache, anxiety, arthritis, asthma.
Because ambroxol hydrochloride has extremely strong bitterness, limit the application of old man and child, directly adding correctives effectively can not cover bitterness.
Summary of the invention
The invention provides a kind of Ambroxol Hydrochloride Granules, this Ambroxol Hydrochloride Granules related impurities content is low and storage ability good.
Present invention also offers a kind of preparation method of Ambroxol Hydrochloride Granules, this preparation method substantially increases the qualification rate of product.
A kind of Ambroxol Hydrochloride Granules, be made up of the component of following weight portion:
Described binding agent is that the hypromellose of 1:0.5 ~ 1 and No. II, acrylic resin form by mass ratio.
The present invention adopts hypromellose and No. II, acrylic resin as binding agent, wherein No. II, acrylic resin has highly filled, low viscous advantage, in the process preparing Ambroxol Hydrochloride Granules, while shortening the time, also not easily there is tablet adhesion and sticky pot.Both combine, and no matter are all improved largely in hardness, moisture or stability etc., and considerably reduce the hygroscopic effect in storage process.
No. II, described acrylic resin is a kind of enteric acrylate's resin, methacrylic acid and methyl methacrylate is adopted to obtain with the ratio copolymerization of mol ratio 50:50, insoluble in the medium of pH2 ~ 5, dissolve in the medium of pH6 ~ 8, can directly buy from the market.
As preferably, the viscosity of described hypromellose is 4000 ~ 6000mPa.s.Adopt No. II, the hypromellose of this viscosity and acrylic resin to match, dissolution and the mobility of described Ambroxol Hydrochloride Granules can be improved.
As preferably, described correctives is steviosin.Adopt steviosin as correctives, mouthfeel can be improved preferably, and not sugary, and diabetics also can be taken, and expands the applicable crowd of medicine, meanwhile, not easily produces harmful substance under high temperature.
Consider the mouthfeel of medicine, impurity content and stability, conduct further preferably, described Ambroxol Hydrochloride Granules, be made up of the component of following weight portion:
Present invention also offers the preparation method of above-mentioned Ambroxol Hydrochloride Granules, comprise the following steps:
(1) take hypromellose and No. II, acrylic resin, under continuous stirring state, slowly adding distilled water, to make mass concentration be 1 ~ 3% aqueous dispersion, puts in liquid spraying can for subsequent use;
(2) ambroxol hydrochloride is dropped into fluid bed, regulate inlet temperature, leaving air temp, feed rate, spray, after forming microcapsule, cross 20 ~ 30 mesh sieves, then drop into mannitol, correctives spraying mix homogeneously, 50 ~ 60 DEG C of oven dry, 20 ~ 30 mesh sieve granulate, obtain described Ambroxol Hydrochloride Granules.
Adopt this preparation method to make medicament microcapsule, medicament microcapsuleization can reduce poisonous side effect of medicine, covers bad smell and taste, improves the stability of medicine in the intestines and stomach or the zest reduced stomach.When patient takes, microcapsule can not discharge medicine because making an exception and occur bitterness, and in gastric juice, capsule material is rapidly dissolvable, release medicine, to reach the object covering ambroxol hydrochloride bitterness.
As preferably, described inlet temperature is 60 DEG C ~ 80 DEG C.
As preferably, described leaving air temp is 50 DEG C ~ 70 DEG C.Adopt this inlet temperature and leaving air temp to be convenient to make medicament microcapsule, and effectively prevent impurity content from raising.
As preferably, described feed rate 5 ~ 15ml/min.
Compared with the existing technology, the invention has the advantages that:
(1) by the screening of adjuvant, can not only avoid wall sticking phenomenon, improve the obtained quality index such as ambroxol hydrochloride microorganism limitation, dissolubility all qualified, moisture, stable content are controlled, also reduce the hygroscopic effect in storage process.
(2) Ambroxol Hydrochloride Granules of the present invention is granulated with microencapsulation, can reduce poisonous side effect of medicine, covers bad smell and taste, improves the stability of medicine in the intestines and stomach or the zest reduced stomach.
(3) preparation method of the present invention is simple, and drying time is short, with short production cycle, and without the need to any special installation, cost is low, is suitable for suitability for industrialized production.
Detailed description of the invention
Embodiment 1
Crude drug and adjuvant are crossed 100 mesh sieves respectively, for subsequent use.
Take the raw material of following recipe quantity:
Take hypromellose 0.02g(model: HT-K, viscosity: 4000mPa.s) and No. II, acrylic resin (manufacturer: Xi'an rehabilitation Pharmaceuticals Ltd of Zao Lutang Pharmaceutical group, medicinal) 0.03g, under continuous stirring state, slowly add distilled water make quality and be divided into 2% aqueous dispersion, put in liquid spraying can for subsequent use.Ambroxol hydrochloride 0.3g is dropped into fluid bed, inlet temperature is 60 DEG C ~ 80 DEG C, leaving air temp is 50 DEG C ~ 70 DEG C, feed rate 10ml/min, sprays, and crosses 30 mesh sieves after forming microcapsule, drop into mannitol 9g, steviosin 0.1g again to spray mix homogeneously, 50 ~ 60 DEG C of oven dry, 20 mesh sieve granulate, obtain Ambroxol Hydrochloride Granules 1000 bags.
Embodiment 2
Crude drug and adjuvant are crossed 100 mesh sieves respectively, for subsequent use.
Take the raw material of following recipe quantity:
Take hypromellose 0.02g(model: HT-K, viscosity: 6000mPa.s) and No. II, acrylic resin (manufacturer: Xi'an rehabilitation Pharmaceuticals Ltd of Zao Lutang Pharmaceutical group, medicinal) 0.03g, under continuous stirring state, slowly add distilled water make quality and be divided into 2% aqueous dispersion, put in liquid spraying can for subsequent use.Ambroxol hydrochloride 0.4g is dropped into fluid bed, inlet temperature is 60 DEG C ~ 80 DEG C, leaving air temp is 50 DEG C ~ 70 DEG C, feed rate 10ml/min, sprays, and crosses 30 mesh sieves after forming microcapsule, drop into mannitol 8g, steviosin 0.1g again to spray mix homogeneously, 50 ~ 60 DEG C of oven dry, 20 mesh sieve granulate, obtain Ambroxol Hydrochloride Granules 1000 bags.
Embodiment 3
Crude drug and adjuvant are crossed 100 mesh sieves respectively, for subsequent use.
Take the raw material of following recipe quantity:
Take hypromellose 0.02g(model: HT-K, viscosity: 2000mPa.s) and No. II, acrylic resin (manufacturer: Xi'an rehabilitation Pharmaceuticals Ltd of Zao Lutang Pharmaceutical group, medicinal) 0.03g, under continuous stirring state, slowly add distilled water make quality and be divided into 2% aqueous dispersion, put in liquid spraying can for subsequent use.Ambroxol hydrochloride 0.5g is dropped into fluid bed, inlet temperature is 60 DEG C ~ 80 DEG C, leaving air temp is 50 DEG C ~ 70 DEG C, feed rate 10ml/min, sprays, and crosses 30 mesh sieves after forming microcapsule, drop into mannitol 8g, steviosin 0.2g again to spray mix homogeneously, 50 ~ 60 DEG C of oven dry, 20 mesh sieve granulate, obtain Ambroxol Hydrochloride Granules 1000 bags.
Embodiment 4
Crude drug and adjuvant are crossed 100 mesh sieves respectively, for subsequent use.
Take the raw material of following recipe quantity:
Take hypromellose 0.02g(model: HT-K, viscosity: 8000mPa.s) and No. II, acrylic resin (manufacturer: Xi'an rehabilitation Pharmaceuticals Ltd of Zao Lutang Pharmaceutical group, medicinal) 0.03g, under continuous stirring state, slowly add distilled water make quality and be divided into 2% aqueous dispersion, put in liquid spraying can for subsequent use.Ambroxol hydrochloride 0.2g is dropped into fluid bed, inlet temperature is 60 DEG C ~ 80 DEG C, leaving air temp is 50 DEG C ~ 70 DEG C, feed rate 10ml/min, sprays, and crosses 30 mesh sieves after forming microcapsule, drop into mannitol 10g, steviosin 0.1g again to spray mix homogeneously, 50 ~ 60 DEG C of oven dry, 20 mesh sieve granulate, obtain Ambroxol Hydrochloride Granules 1000 bags.
Comparative example 1
Comparative example 2
Comparative example 3
The preparation technology of comparative example 1 ~ 3 is as follows:
Principal agent and adjuvant are crossed 100 mesh sieves respectively.First adjuvant is fully mixed, then take recipe quantity adjuvant and fully mix with principal agent.Add binding agent soft material again, 20 mesh sieves are granulated, 55 DEG C of dryings, and 20 mesh sieve granulate, sift out fine powder, packaging.
Comparative example 4
All operations are identical with embodiment 1, except binding agent only uses hypromellose.
Comparative example 5
All operations are identical with embodiment 1, except No. II, acrylic resin is replaced with Eudragit Ⅲ.
Comparative example 6
All operations are identical with embodiment 1, except hypromellose is replaced with polyvidone.
The Ambroxol Hydrochloride Granules that the embodiment of the present invention 1 ~ 4 and comparative example 1 ~ 6 obtain is carried out stability test, and adopt the method for accelerated test to carry out study on the stability to it, the detection method of projects is all pressed
According to the record method in Chinese Pharmacopoeia version two in 2010, result is as following table:
The related check data of Ambroxol Hydrochloride Granules
Result shows: sample is placed 6 months under accelerated test condition, and its character, granularity, moisture, dissolution, related substance, content etc. are all better than comparative example 1 ~ 3(and publication number is the Chinese patent application of CN1836654A) tablet prepared.With short production cycle, quality controllable, be beneficial to cost-saving, and simple to operate, meet industrialization production requirements, be better than existing preparation method.
Claims (7)
1. an Ambroxol Hydrochloride Granules, is characterized in that, is made up of the component of following weight portion:
Described binding agent is that the hypromellose of 1:0.5 ~ 1 and No. II, acrylic resin form by mass ratio;
The preparation method of described Ambroxol Hydrochloride Granules, comprises the following steps:
(1) take hypromellose and No. II, acrylic resin, under continuous stirring state, slowly adding distilled water, to make mass concentration be 1 ~ 3% aqueous dispersion, puts in liquid spraying can for subsequent use;
(2) ambroxol hydrochloride is dropped into fluid bed, regulate inlet temperature, leaving air temp, feed rate, sprays, and crosses 20 ~ 30 mesh sieves after forming microcapsule, drop into mannitol, correctives spraying mix homogeneously again, 50 ~ 60 DEG C of oven dry, 20 ~ 30 mesh sieve granulate, obtain described Ambroxol Hydrochloride Granules.
2. Ambroxol Hydrochloride Granules according to claim 1, is characterized in that, the viscosity of described hypromellose is 4000 ~ 6000mPa.s.
3. Ambroxol Hydrochloride Granules according to claim 1 and 2, is characterized in that, described correctives is steviosin.
4. Ambroxol Hydrochloride Granules according to claim 3, is characterized in that, is made up of the component of following weight portion:
5. Ambroxol Hydrochloride Granules according to claim 1, is characterized in that, described inlet temperature is 60 DEG C ~ 80 DEG C.
6. Ambroxol Hydrochloride Granules according to claim 1, is characterized in that, described leaving air temp is 50 DEG C ~ 70 DEG C.
7. Ambroxol Hydrochloride Granules according to claim 1, is characterized in that, described feed rate 5 ~ 15ml/min.
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| CN201310491704.9A CN103565753B (en) | 2013-10-18 | 2013-10-18 | Ambroxol Hydrochloride Granules and preparation method thereof |
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| CN201310491704.9A CN103565753B (en) | 2013-10-18 | 2013-10-18 | Ambroxol Hydrochloride Granules and preparation method thereof |
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| CN103565753A CN103565753A (en) | 2014-02-12 |
| CN103565753B true CN103565753B (en) | 2015-09-16 |
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| CN104606170A (en) * | 2015-02-04 | 2015-05-13 | 上海华源安徽仁济制药有限公司 | Ambroxol hydrochloride capsule and preparation method thereof |
| CN105726560B (en) * | 2016-01-26 | 2019-04-16 | 海南葫芦娃药业集团股份有限公司 | A kind of Gansukang capsule and preparation method thereof |
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Address after: Haikou national high tech Zone Industrial Park two trough trough four road 570216 Hainan city of Haikou province No. 8 Patentee after: HAINAN HULUWA PHARMACEUTICAL GROUP CO., LTD. Address before: Haikou national high tech Zone Industrial Park two trough trough four road 570216 Hainan city of Haikou province No. 8 Patentee before: Hainan Gourd Doll Pharmaceutical Co., Ltd. |