CN105708840A - Epinastine hydrochloride composition - Google Patents
Epinastine hydrochloride composition Download PDFInfo
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- CN105708840A CN105708840A CN201410710953.7A CN201410710953A CN105708840A CN 105708840 A CN105708840 A CN 105708840A CN 201410710953 A CN201410710953 A CN 201410710953A CN 105708840 A CN105708840 A CN 105708840A
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- epinastine hydrochloride
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Abstract
The invention discloses an epinastine hydrochloride composition. In terms of 1000 weight parts, the prescription of the composition involves 15-50 parts by weight of epinastine hydrochloride, 830-950 parts by weight of filler, 25-60 parts by weight of a composite flavoring agent, 0.5-5 parts by weight of hydroxypropyl cellulose, 0.5-5 parts by weight of essence. The invention adopts the composite flavoring agent for taste modifying, also selects the filler with sweet taste, and is supplemented by essence, effectively covers up the disadvantage of extremely bitter taste of epinastine hydrochloride, and improves the clinical medication compliance. The invention effectively solves the problems of large particle size distribution and much particle fine powder in epinastine hydrochloride composition, can obtain stable and uniform particles, and is suitable for industrial production requirements.
Description
Technical field
The present invention relates to epinastine, be specifically related to a kind of epinastine hydrochloride compositions.
Background technology
Epinastine hydrochloride is efficient selective H1Acceptor inhibitor, its tablet has been thrown in from 1994 since Japanese market, due to the feature such as it is respond well, safety is high, indication scope is wide, drug interaction is few and cardiac toxicity is low, being always up the leading products in the oral allergy preparations of Japan, the various dosage form such as capsule, eye drop develops listing in succession.
Epinastine hydrochloride taste is extremely bitter, therefore it mostly is coated tablet or capsule clinically, due to this product few side effects, toxicity is low, patient's better tolerance, in Japan for department of pediatrics or particular patient medication, develop 1% epinastine hydrochloride dry syrup, get permission to produce in Japan in January, 2005, it it is the novel form aiming at department of pediatrics or particular patient use and developing, it is first once-a-day medication of Japan, it is suitable for department of pediatrics or the Loratadine of particular patient use, this product is got permission for bronchial asthma, abnormality rhinitis, rubella, the treatment of the allergic diseases such as skin pruritus (includes eczema), convenient oral, market potential is big.
It is extremely bitter that epinastine hydrochloride is dissolved in water aftertaste, and single correctives is difficult to cover its bitterness, and after correctives large usage quantity, increases the difficulty of granulation, it is difficult to is uniformly mixed and granule that particle size distribution is narrower, is unfavorable for that preparation produces.
Summary of the invention
For the problems referred to above that prior art exists, it is an object of the invention to provide a kind of epinastine hydrochloride granula subtilis.
For achieving the above object, the technical solution used in the present invention is as follows:
A kind of epinastine hydrochloride compositions, is made up of by following proportioning epinastine hydrochloride, filler, compound correctives, binding agent and essence:
Epinastine hydrochloride 5～40 weight portion；
Filler 820～950 weight portion；
Compound correctives 25～60 weight portion；
Binding agent 1～5 weight portion；
Essence 0.5～5 weight portion.
Above-mentioned compound correctives is the mixture of aspartame, sucralose and glycyrrhizic acid monoammonium S.
The filler of the present invention is the good adjuvant of water solublity.
Above-mentioned binding agent is preferably any one in hydroxypropyl cellulose, polyvidone and starch.
As a kind of preferred version, the composition and ratio of described epinastine hydrochloride compositions is as follows:
Epinastine hydrochloride 5～30 weight portion；
Filler 870～950 weight portion；
Compound correctives 30～50 weight portion；
Binding agent 2～4 weight portion；
Essence 1～3 weight portion；
The weight portion sum of above-mentioned each composition is 1000 weight portions.
As a kind of optimal case, the composition and ratio of described epinastine hydrochloride compositions is as follows:
Epinastine hydrochloride 10 weight portion；
Filler 945 weight portion；
Compound correctives 40 weight portion；
Binding agent 3 weight portion；
Essence 2 weight portion.
Above-mentioned filler selects the good adjuvant of water-soluble, it is preferred to one in erythritol, sucrose or its compositions.
Above-mentioned correctives is preferably the homogeneous mixture of aspartame, sucralose and glycyrrhizic acid monoammonium S, and its ratio is 8:1:1.
Above-mentioned binding agent is preferably any one in hydroxypropyl cellulose, polyvidone and starch.
Above-mentioned essence is preferably any one in strawberry essence, flavoring pineapple essence, fragrant citrus essence and milk flavour.
Above-mentioned composition is preferred with granula subtilis.
The preparation method of epinastine hydrochloride granula subtilis of the present invention is as follows:
First by the epinastine hydrochloride of recipe quantity, filler, compound correctives mix homogeneously, the aqueous solution being subsequently adding binding agent carries out wet granulation, dry, rear granulate, then spray into suitable amount of adhesive solution and carry out fluidized bed granulation, dry, finally mix homogeneously with essence, after granule subpackage, obtain finished product.
Preferably, the diameter of particle of described epinastine hydrochloride and filler, correctives is respectively less than equal to 120 orders.
Preferably, it is 5～20% for the mass percent concentration of the binder aqueous solution of wet granulation.
Preferably, dry selection fluid bed drying, baking temperature is 50～80 DEG C, and drying time is 15～40 minutes.
Preferably, the mesh size that granulate is selected is 0.5-1.0mm.
Preferably, it is 1～3% for the mass percent concentration of the binder aqueous solution of fluidized bed granulation.
Compared with prior art, the beneficial effects of the present invention is:
The present invention is by adopting compound taste masking technology to carry out taste masking, and selects the filler with sweet taste.Selected filler, correctives and essence produce synergism, efficiently solve the shortcoming that epinastine hydrochloride taste is extremely bitter, improve the compliance of clinical application.In prescription of the present invention, correctives large usage quantity, filler becomes crystalloid, and water carrying capacity is relatively low, and direct wet granulation is difficult to obtain the granule of uniform particle diameter, granule heterogeneity, affects bigger on the drug content in finished product.The present invention, by wet granulation, granulate, fluidized bed granulation combination, significantly reduces particle size distribution scope.It is relatively big that the present invention efficiently solves epinastine hydrochloride particulate particle size distribution, the problem that granule fines is more, stablize, homogeneous granule, applicable industrialization production requirements.The compositions composition of the present invention is simple, and adjuvant is cheap and easy to get, and preparation is easily, it is not necessary to special installation, with short production cycle, cost is low, is also very suitable for industrialized production；In a word, the present invention has significance progress relative to prior art.
Detailed description of the invention
Below in conjunction with embodiment and comparative example, technical solution of the present invention is described in further detail and completely.
Embodiment 1:
The composition prescription of granula subtilis described in the present embodiment is as follows:
Epinastine hydrochloride 100g
Sucrose 9438g
Aspartame 320g
Sucralose 40g
Glycyrrhizic acid monoammonium S40g
Hydroxypropyl cellulose 42g
Strawberry essence 20g.
First described epinastine hydrochloride, sucrose, aspartame, sucralose, glycyrrhizic acid monoammonium S are crossed respectively 120 mesh sieves, standby；Then the epinastine hydrochloride of recipe quantity is put in wet granulator with sucrose aspartame, sucralose, glycyrrhizic acid monoammonium S, open stirring 5min and be sufficiently mixed uniformly to each material.Then add 5%(w/w) hydroxypropyl cellulose aqueous solution 600g make binding agent granulate.Fluid bed drying to water content lower than 3% time mesh size be the screen cloth granulate of 0.5mm.In fluid bed, spray into 2%(w/w again) hydroxypropyl cellulose aqueous solution 600g make binding agent granulate, dried granulate, add strawberry essence, mix homogeneously, be distributed into dimension, to obtain final product.
Embodiment 2
The composition prescription of granula subtilis described in the present embodiment is as follows:
Epinastine hydrochloride 100g
Erythritol 9438g
Aspartame 320g
Sucralose 40g
Glycyrrhizic acid monoammonium S40g
Hydroxypropyl cellulose 42g
Milk flavour 20g；
First described epinastine hydrochloride, erythritol, aspartame, sucralose, glycyrrhizic acid monoammonium S are crossed respectively 120 mesh sieves, standby；Then the epinastine hydrochloride of recipe quantity is put in wet granulator with sucrose aspartame, sucralose, glycyrrhizic acid monoammonium S, open stirring 5min and be sufficiently mixed uniformly to each material.Then add 5%(w/w) hydroxypropyl cellulose aqueous solution 600g make binding agent granulate.Fluid bed drying to water content lower than 3% time mesh size be the screen cloth granulate of 0.5mm.In fluid bed, spray into 2%(w/w again) hydroxypropyl cellulose aqueous solution 600g make binding agent granulate, dried granulate, add milk flavour, mix homogeneously, be distributed into dimension, to obtain final product.
Embodiment 3
The composition prescription of granula subtilis described in the present embodiment is as follows:
Epinastine hydrochloride 100g
Erythritol 4438g
Sucrose 5000g
Aspartame 320g
Sucralose 40g
Glycyrrhizic acid monoammonium S40g
Hydroxypropyl cellulose 42g
Flavoring pineapple essence 20g；
First described epinastine hydrochloride, erythritol, sucrose, aspartame, sucralose, glycyrrhizic acid monoammonium S are crossed respectively 120 mesh sieves, standby；Then the epinastine hydrochloride of recipe quantity is put in wet granulator with sucrose aspartame, sucralose, glycyrrhizic acid monoammonium S, open stirring 5min and be sufficiently mixed uniformly to each material.Then add 5%(w/w) hydroxypropyl cellulose aqueous solution 600g make binding agent granulate.Fluid bed drying to water content lower than 3% time mesh size be the screen cloth granulate of 0.5mm.In fluid bed, spray into 2%(w/w again) hydroxypropyl cellulose aqueous solution 600g make binding agent granulate, dried granulate, add flavoring pineapple essence, mix homogeneously, be distributed into dimension, obtain the granula subtilis less than 30 orders.
Embodiment 4
Choosing 30 orders, 65 orders, 120 orders, 250 orders, Example 1-3 gained granula subtilis 100g, be respectively put in screen jacket, two handss are uniformly exerted oneself, and vibrate 5 minutes, open top cover, weigh the granule weight on sieve at different levels respectively, calculate each several part granule and account for the ratio of total stuff amount.Record each several part particle diameter accounting as shown in table 1.
Finished particle particle size distribution obtained by table 1 above-described embodiment and technique
Table 1 data show, granula subtilis prepared by the formulation and technology described in embodiment 1 ~ 3, particle size distribution is substantially between 30 orders to 200 orders, and major part granule is between 65 orders to 120 orders, less than 200 order fine powder accountings within 4%, particle size distribution scope is narrower, and granulating efficiency is better, it is possible to meet the requirement of subsequent technique.
Embodiment 5
By 2010 editions two annex I rules of preparations IN of Chinese Pharmacopoeia, above-described embodiment and comparative example gained granula subtilis are carried out quality inspection；Mouthfeel evaluation is participated in crowd and is included adult man, each 10 of female, child's (below 12 one full year of life) man, each 10 of female；Detailed Inspection result is shown in Table 2.
The quality test results of table 2 above-described embodiment and comparative example gained granula subtilis
Table 2 data show, granula subtilis prepared by the formulation and technology described in embodiment 1 ~ 3, loss on drying, content, have three key indexs of related substance all to meet 2010 editions ruless of preparations of Chinese Pharmacopoeia regulation；The granula subtilis mouthfeel evaluation prepared is better；The granula subtilis good fluidity prepared.Quality test results totally meets regulation.
Example 1-3 gained granula subtilis keeps sample for a long time respectively under temperature 25 DEG C ± 2 DEG C, relative humidity 60% ± 10% condition, investigates its shelf stability.Table 3 is embodiment 2-5 gained granula subtilis quality measurements after certain period that keeps sample.
Table 3 granula subtilis Detection of Stability result
Table 3 data show, granula subtilis prepared by the formulation and technology described in embodiment 1 ~ 3, long-term stable experiment is carried out under temperature 25 DEG C ± 2 DEG C, relative humidity 60% ± 10% condition, detect respectively at March, June, JIUYUE, December, 18 months, 24 months six time points respectively, sample property, content, have related substance all to meet regulation；Stability study sample mouthfeel is better, it was shown that it is good that sample imitated phase internal stability at 24 months.
Embodiment 6-10
Running according to parameter in below table, with parts by weight, all the other are with reference to embodiment 1
| Epinastine | Filler | Compound correctives | Binding agent | Essence | |
| Embodiment 6 | 15 | 950 | 25 | 5 | 5 |
| Embodiment 7 | 50 | 882 | 60 | 5 | 3 |
| Embodiment 8 | 20 | 940 | 35 | 4 | 1 |
| Embodiment 9 | 40 | 900 | 50 | 5 | 5 |
| Embodiment 10 | 30 | 925 | 40 | 3 | 2 |
The formula that the granula subtilis that embodiment of the present invention 6-10 prepares is selected is reasonable, and filler, correctives and essence produce synergism, efficiently solves the shortcoming that aspartame taste is extremely bitter, improves the compliance of clinical application.The present invention, by wet granulation, granulate, fluidized bed granulation combination, significantly reduces particle size distribution scope.Through detection, epinastine granula subtilis particle size distribution prepared by the present invention is suitable, is suitable for granulating；Good stability, prepared granula subtilis is up-to-standard.
The composition of granula subtilis of the present invention is simple, and adjuvant is cheap and easy to get, and preparation is easily, it is not necessary to special installation, with short production cycle, cost is low, is also very suitable for industrialized production；In a word, the present invention has significance progress relative to prior art.
Finally it is necessary described herein: above example is served only for technical scheme is described in more detail; it is not intended that limiting the scope of the invention, some nonessential improvement and adjustment that those skilled in the art makes according to the foregoing of the present invention belong to protection scope of the present invention.
Claims (9)
1. an epinastine hydrochloride compositions, it is characterised in that: prepared by following proportioning by epinastine hydrochloride, filler, compound correctives, binding agent and essence:
Epinastine hydrochloride 5～40 weight portion；
Filler 820～950 weight portion；
Compound correctives 25～60 weight portion；
Binding agent 1～5 weight portion；
Essence 0.5～5 weight portion；
Described compound correctives is the homogeneous mixture of aspartame, sucralose and glycyrrhizic acid monoammonium S；The weight portion sum of described each composition is 1000 weight portions.
2. epinastine hydrochloride compositions as claimed in claim 1, it is characterised in that there is following composition and ratio:
Epinastine hydrochloride 5～30 weight portion；
Filler 870～950 weight portion；
Compound correctives 30～50 weight portion；
Binding agent 2～4 weight portion；
Essence 1～3 weight portion；
The weight portion sum of described each composition is 1000 weight portions.
3. epinastine hydrochloride compositions as claimed in claim 1, it is characterised in that: described filler is selected from the one in sucrose, erythritol or both compositionss.
4. epinastine hydrochloride compositions as claimed in claim 2, it is characterised in that: described filler is selected from the one in sucrose, erythritol or both compositionss.
5. epinastine hydrochloride compositions as claimed in claim 1, it is characterised in that: described compound correctives be aspartame, sucralose, glycyrrhizic acid monoammonium S ratio for 8:1:1, by weight.
6. epinastine hydrochloride compositions as claimed in claim 2, it is characterised in that: described compound correctives be aspartame, sucralose, glycyrrhizic acid monoammonium S ratio for 8:1:1, by weight.
7. epinastine hydrochloride compositions as claimed in claim 1 or 2, it is characterised in that: described binding agent is selected from any one in hydroxypropyl cellulose, polyvidone or starch.
8. epinastine hydrochloride compositions as claimed in claim 1 or 2, it is characterised in that: described essence is selected from any one in strawberry essence, flavoring pineapple essence, fragrant citrus essence or milk flavour.
9. the epinastine hydrochloride compositions as described in any one of claim 1-6, it is characterised in that: described compositions is granula subtilis.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410710953.7A CN105708840A (en) | 2014-12-01 | 2014-12-01 | Epinastine hydrochloride composition |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410710953.7A CN105708840A (en) | 2014-12-01 | 2014-12-01 | Epinastine hydrochloride composition |
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| CN105708840A true CN105708840A (en) | 2016-06-29 |
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| CN201410710953.7A Pending CN105708840A (en) | 2014-12-01 | 2014-12-01 | Epinastine hydrochloride composition |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1202111A (en) * | 1995-11-14 | 1998-12-16 | 贝林格尔·英格海姆公司 | Use of epinastine in the treatment of pain |
| WO2003037350A1 (en) * | 2001-10-26 | 2003-05-08 | Boehringer Ingelheim International Gmbh | New dry and aqueous epinastine-syrup-formulation |
| CN1981769A (en) * | 2005-12-16 | 2007-06-20 | 张文静 | Hydrochloride epinastine dispersing tablets and their production |
| CN103251563A (en) * | 2013-05-22 | 2013-08-21 | 北京科源创欣科技有限公司 | Stable granular medicine composition containing epinastine or hydrochloride thereof |
-
2014
- 2014-12-01 CN CN201410710953.7A patent/CN105708840A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1202111A (en) * | 1995-11-14 | 1998-12-16 | 贝林格尔·英格海姆公司 | Use of epinastine in the treatment of pain |
| WO2003037350A1 (en) * | 2001-10-26 | 2003-05-08 | Boehringer Ingelheim International Gmbh | New dry and aqueous epinastine-syrup-formulation |
| CN1981769A (en) * | 2005-12-16 | 2007-06-20 | 张文静 | Hydrochloride epinastine dispersing tablets and their production |
| CN103251563A (en) * | 2013-05-22 | 2013-08-21 | 北京科源创欣科技有限公司 | Stable granular medicine composition containing epinastine or hydrochloride thereof |
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