CN102247368A - Compound acrivastine sustained release tablets, and preparation method thereof - Google Patents
Compound acrivastine sustained release tablets, and preparation method thereof Download PDFInfo
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- CN102247368A CN102247368A CN 201110130629 CN201110130629A CN102247368A CN 102247368 A CN102247368 A CN 102247368A CN 201110130629 CN201110130629 CN 201110130629 CN 201110130629 A CN201110130629 A CN 201110130629A CN 102247368 A CN102247368 A CN 102247368A
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- Prior art keywords
- acrivastine
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- hydroxypropyl emthylcellulose
- slow releasing
- pseudoephedrine hydrochloride
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- 229960003792 acrivastine Drugs 0.000 title claims abstract description 46
- PWACSDKDOHSSQD-IUTFFREVSA-N acrivastine Chemical compound C1=CC(C)=CC=C1C(\C=1N=C(\C=C\C(O)=O)C=CC=1)=C/CN1CCCC1 PWACSDKDOHSSQD-IUTFFREVSA-N 0.000 title claims abstract description 46
- 150000001875 compounds Chemical class 0.000 title claims abstract description 33
- 238000002360 preparation method Methods 0.000 title claims abstract description 25
- 239000007939 sustained release tablet Substances 0.000 title abstract description 4
- 239000008187 granular material Substances 0.000 claims abstract description 25
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims abstract description 22
- KWGRBVOPPLSCSI-UHFFFAOYSA-N d-ephedrine Natural products CNC(C)C(O)C1=CC=CC=C1 KWGRBVOPPLSCSI-UHFFFAOYSA-N 0.000 claims abstract description 17
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims abstract description 16
- 239000008101 lactose Substances 0.000 claims abstract description 15
- BALXUFOVQVENIU-KXNXZCPBSA-N pseudoephedrine hydrochloride Chemical compound [H+].[Cl-].CN[C@@H](C)[C@@H](O)C1=CC=CC=C1 BALXUFOVQVENIU-KXNXZCPBSA-N 0.000 claims abstract description 13
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims abstract description 12
- 229960003447 pseudoephedrine hydrochloride Drugs 0.000 claims abstract description 12
- 235000019359 magnesium stearate Nutrition 0.000 claims abstract description 11
- 239000000203 mixture Substances 0.000 claims abstract description 9
- 239000007779 soft material Substances 0.000 claims abstract description 9
- 239000002994 raw material Substances 0.000 claims abstract description 6
- 239000000377 silicon dioxide Substances 0.000 claims abstract description 6
- 235000012239 silicon dioxide Nutrition 0.000 claims abstract description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 24
- -1 Hydroxypropyl Chemical group 0.000 claims description 20
- 238000000034 method Methods 0.000 claims description 16
- 239000003814 drug Substances 0.000 claims description 15
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 12
- 239000011230 binding agent Substances 0.000 claims description 11
- 229940079593 drug Drugs 0.000 claims description 10
- 238000002156 mixing Methods 0.000 claims description 7
- 238000005303 weighing Methods 0.000 claims description 7
- 229910004298 SiO 2 Inorganic materials 0.000 claims description 5
- 238000001514 detection method Methods 0.000 claims description 5
- 239000000843 powder Substances 0.000 claims description 5
- 229960001375 lactose Drugs 0.000 claims description 4
- 238000012856 packing Methods 0.000 claims description 3
- 238000004080 punching Methods 0.000 claims description 3
- 239000003826 tablet Substances 0.000 abstract description 43
- 239000000463 material Substances 0.000 abstract description 10
- SQXPPECBPHSOSQ-GNWPWZHSSA-N (1s,2s)-2-(methylamino)-1-phenylpropan-1-ol;(e)-3-[6-[(e)-1-(4-methylphenyl)-3-pyrrolidin-1-ylprop-1-enyl]pyridin-2-yl]prop-2-enoic acid;hydrochloride Chemical compound Cl.CN[C@@H](C)[C@@H](O)C1=CC=CC=C1.C1=CC(C)=CC=C1C(\C=1N=C(\C=C\C(O)=O)C=CC=1)=C/CN1CCCC1 SQXPPECBPHSOSQ-GNWPWZHSSA-N 0.000 abstract description 4
- 239000000314 lubricant Substances 0.000 abstract description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 abstract 3
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 abstract 3
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 abstract 3
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 abstract 3
- 206010067484 Adverse reaction Diseases 0.000 abstract 1
- 239000000853 adhesive Substances 0.000 abstract 1
- 230000001070 adhesive effect Effects 0.000 abstract 1
- 230000006838 adverse reaction Effects 0.000 abstract 1
- 229910052681 coesite Inorganic materials 0.000 abstract 1
- 229910052906 cristobalite Inorganic materials 0.000 abstract 1
- 229910052682 stishovite Inorganic materials 0.000 abstract 1
- 229910052905 tridymite Inorganic materials 0.000 abstract 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- 238000005516 engineering process Methods 0.000 description 6
- 238000012216 screening Methods 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 239000000945 filler Substances 0.000 description 4
- 230000001387 anti-histamine Effects 0.000 description 3
- 239000000739 antihistaminic agent Substances 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000003825 pressing Methods 0.000 description 3
- 238000010561 standard procedure Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- KWGRBVOPPLSCSI-WPRPVWTQSA-N (-)-ephedrine Chemical compound CN[C@@H](C)[C@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WPRPVWTQSA-N 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 238000007599 discharging Methods 0.000 description 2
- 238000005469 granulation Methods 0.000 description 2
- 230000003179 granulation Effects 0.000 description 2
- 238000005286 illumination Methods 0.000 description 2
- 238000007689 inspection Methods 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 238000005453 pelletization Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- HDLOXDDMKWEDCR-PASALVRNSA-N (1s,2s)-2-(methylamino)-1-phenylpropan-1-ol;(e)-3-[6-[(e)-1-(4-methylphenyl)-3-pyrrolidin-1-ylprop-1-enyl]pyridin-2-yl]prop-2-enoic acid Chemical compound CN[C@@H](C)[C@@H](O)C1=CC=CC=C1.C1=CC(C)=CC=C1C(\C=1N=C(\C=C\C(O)=O)C=CC=1)=C/CN1CCCC1 HDLOXDDMKWEDCR-PASALVRNSA-N 0.000 description 1
- ZOPQOWMEWBFVAR-PXRPMCEGSA-N 2-[2-[4-[(4-chlorophenyl)-phenylmethyl]piperazin-1-yl]ethoxy]acetic acid;(1s,2s)-2-(methylamino)-1-phenylpropan-1-ol Chemical compound CN[C@@H](C)[C@@H](O)C1=CC=CC=C1.C1CN(CCOCC(=O)O)CCN1C(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 ZOPQOWMEWBFVAR-PXRPMCEGSA-N 0.000 description 1
- 208000035285 Allergic Seasonal Rhinitis Diseases 0.000 description 1
- DBAKFASWICGISY-BTJKTKAUSA-N Chlorpheniramine maleate Chemical compound OC(=O)\C=C/C(O)=O.C=1C=CC=NC=1C(CCN(C)C)C1=CC=C(Cl)C=C1 DBAKFASWICGISY-BTJKTKAUSA-N 0.000 description 1
- 102000000543 Histamine Receptors Human genes 0.000 description 1
- 108010002059 Histamine Receptors Proteins 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 208000036284 Rhinitis seasonal Diseases 0.000 description 1
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 1
- 229940042500 acrivastine / pseudoephedrine Drugs 0.000 description 1
- 229940086148 acrivastine 8 mg Drugs 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 201000010105 allergic rhinitis Diseases 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000002269 analeptic agent Substances 0.000 description 1
- 230000003266 anti-allergic effect Effects 0.000 description 1
- 230000002804 anti-anaphylactic effect Effects 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229940056152 cetirizine / pseudoephedrine Drugs 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 229960002179 ephedrine Drugs 0.000 description 1
- ZQBWEJQBVWJHRY-PXRPMCEGSA-N ethyl 4-(8-chloro-5,6-dihydrobenzo[1,2]cyclohepta[2,4-b]pyridin-11-ylidene)piperidine-1-carboxylate;(1s,2s)-2-(methylamino)-1-phenylpropan-1-ol Chemical compound CN[C@@H](C)[C@@H](O)C1=CC=CC=C1.C1CN(C(=O)OCC)CCC1=C1C2=NC=CC=C2CCC2=CC(Cl)=CC=C21 ZQBWEJQBVWJHRY-PXRPMCEGSA-N 0.000 description 1
- 229940042366 fexofenadine / pseudoephedrine Drugs 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 229940033996 loratadine / pseudoephedrine Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 238000006303 photolysis reaction Methods 0.000 description 1
- 230000015843 photosynthesis, light reaction Effects 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 229940035056 pseudoephedrine hydrochloride 120 mg Drugs 0.000 description 1
- 150000003233 pyrroles Chemical group 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 208000017022 seasonal allergic rhinitis Diseases 0.000 description 1
- 229940115174 semprex-d Drugs 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 238000009492 tablet coating Methods 0.000 description 1
- 239000002700 tablet coating Substances 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
Images
Abstract
The invention relates to compound acrivastine sustained release tablets, which are prepared from formulated raw materials of, by mass: 14 to 18 parts of acrivastine, 118 to 122 parts of pseudoephedrine hydrochloride, 38 to 42 parts of hydroxypropyl methylcellulose K4M, 18 to 22 parts of hydroxypropyl methylcellulose (100mPa.s), 98 to 102 parts of lactose, 1 to 3 parts of magnesium stearate, and 1 to 3 parts of SiO2. The preparation method comprises the steps that: the effective components acrivastine and pseudoephedrine hydrochloride, and the filling material are weighed, sieved and mixed; the framework material hydroxypropyl methylcellulose and an adhesive are added to the mixture; a soft material is prepared and sieved, such that wet granules are prepared; the granules are dried and shaped; a lubricant is added to the granules; all the materials are well mixed and are compressed into tablets according to certain requirements; the tablets are packed, such that finished products are obtained. Compared to common tablets, the sustained release tablets provided by the invention has advantages of long functioning duration, which is 12 hours; mild function; slow release; and less and light adverse reaction.
Description
Technical field
The present invention relates to the medication preparation field, relate in particular to a kind of compound recipe acrivastine slow releasing tablet and preparation method thereof.
Background technology
Acrivastine is pyrroles's amine antihistaminic, is by Britain Glaxo-Wellcome company development, its capsule preparations in August, 1988 in Britain's Initial Public Offering, commodity are called Semprex.The acrivastine capsule was going on the market in China through approval in 1993, and obtained administrative protection in 93 years, and the calendar year 2001 administrative protection of this kind stops, and its commodity are called glad folk music.
Compound recipe acrivastine capsule is the compound preparation of acrivastine 8mg and the pseudo-numb alkali 60mg of hydrochloric acid.Antihistamine new drug acrivastine in this product plays anti-allergic effects, and β
2The pseudo-fiber crops of receptor stimulating agent hydrochloric acid play the effect of the congested allergic symptom of rapid releasing nose, therefore have the incomparable clear superiority of folk prescription.The compound preparation application for quotation of acrivastine that in March, 1994, UCB. S.A. (BE) Bruxelles Belgium submitted to U.S. FDA and the pseudo-Herba Ephedrae of hydrochloric acid gets the Green Light, and commodity are called Semprex-D.The domestic report that does not still have listing at present of this kind.
The compound preparation of the pseudo-numb alkali of antihistaminic and hydrochloric acid has been antianaphylactic treatment medicine medicine compatibility method the most commonly used, and such compound preparation that has gone on the market has: loratadine/pseudoephedrine hydrochloride, fexofenadine/pseudoephedrine hydrochloride, chlorphenamine maleate/pseudoephedrine hydrochloride, cetirizine/pseudoephedrine hydrochloride etc.The compound preparation of acrivastine and pseudoephedrine hydrochloride can play rapid controlling symptoms, pick up the effect that anti-effect reaches treating both the principal and secondary aspects of a disease by the histamine receptor of acrivastine again.Therefore, acrivastine/pseudoephedrine hydrochloride compound preparation is compared with the acrivastine single preparations of ephedrine and is had very significantly curative effect advantage.
At present the weak point of the compound preparation of report be acrivastine and pseudoephedrine hydrochloride the compound preparation employing be ordinary preparation, patient's medicining times many (4-6 times on the one), patient's toleration is poor, bioavailability is low.
Summary of the invention
The invention discloses a kind of compound recipe acrivastine slow releasing tablet and preparation method thereof.The invention is intended to by process innovation, adopt slow release method, make slow releasing tablet, reduce patient's medicining times, the patient is acceptant, has improved bioavailability of medicament simultaneously.
The present invention adopts following technical scheme for achieving the above object:
A kind of compound recipe acrivastine slow releasing tablet is characterized in that: the mass ratio of its each component of prescription raw material is:
Acrivastine: 14-18
Pseudoephedrine hydrochloride: 118-122
Hydroxypropyl emthylcellulose K4M:38-42
Hydroxypropyl emthylcellulose (100mPa.s): 18-22
Lactose: 98-102
Magnesium stearate: 1-3
SiO
2： 1-3
70% ethanol: an amount of.
Described compound recipe acrivastine slow releasing tablet is characterized in that: the mass ratio of its each component of prescription raw material is:
Acrivastine: 16
Pseudoephedrine hydrochloride: 120
Hydroxypropyl emthylcellulose K4M:40
Hydroxypropyl emthylcellulose (100mPa.s): 20
Lactose: 100
Magnesium stearate: 2
SiO
2： 2
70% ethanol: an amount of.
The preparation method of described compound recipe acrivastine slow releasing tablet is characterized in that: specifically may further comprise the steps:
(1) lucifuge operation takes by weighing each supplementary material by prescription, and is standby;
(2) with acrivastine crude drug, pseudoephedrine hydrochloride, lactose, cross behind 100 mesh sieves by the abundant mix homogeneously of equivalent incremental method respectively;
(3) in above-mentioned blended medicated powder, add hydroxypropyl emthylcellulose K4M and hydroxypropyl emthylcellulose (100mPa.s) mixing, make binding agent, the system soft material with an amount of 70% ethanol;
(4) soft material is passed through the wet grain of 20 mesh sieve systems;
(5) granule is put into baking oven, 55-65 ℃ after dry 15-20 minute, take out and naturally cool to room temperature;
(6) dried granule is passed through 20 mesh sieve granulate;
(7) granule mix homogeneously behind the magnesium stearate that will take by weighing, silicon dioxide and the granulate, detection level is calculated and is answered tabletting heavy;
(8) use the tablet machine tabletting, used stamping is No. 10 stampings, pressure 5～6kg;
(9) the good tablet of packing punching press.
Beneficial effect of the present invention:
The compound recipe acrivastine slow releasing tablet acting duration that the present invention produces long (12h), effect relaxes, and discharges slowly steadily, and untoward reaction is few and light, has reduced patient's medication number of times, has improved patient's toleration, has improved patient's bioavailability.
Description of drawings
Fig. 1 is a process chart of the present invention.
Specific embodiments
The prescription prescription and the technology of compound recipe acrivastine slow releasing tablet are as follows:
1. write out a prescription
Acrivastine: 16g
Pseudoephedrine hydrochloride: 120g
Hydroxypropyl emthylcellulose K4M:40g
Hydroxypropyl emthylcellulose (100mPa.s): 20g
Lactose: 100g
Magnesium stearate: 2g
SiO
2： 2g
70% ethanol: an amount of,
Above-mentioned prescription batching is made 1000.
Preparation technology
(1) lucifuge operation takes by weighing each supplementary material by prescription, and is standby;
(2) with acrivastine crude drug, pseudoephedrine hydrochloride, lactose, cross behind 100 mesh sieves by the abundant mix homogeneously of equivalent incremental method respectively;
(3) in above-mentioned blended medicated powder, add hydroxypropyl emthylcellulose K4M and hydroxypropyl emthylcellulose (100mPa.s) mixing, make binding agent, the system soft material with an amount of 70% ethanol;
(4) soft material is passed through the wet grain of 20 mesh sieve systems;
(5) granule is put into baking oven, 55-65 ℃ after dry 15-20 minute, take out and naturally cool to room temperature;
(6) dried granule is passed through 20 mesh sieve granulate;
(7) granule mix homogeneously behind the magnesium stearate that will take by weighing, silicon dioxide and the granulate, detection level is calculated and is answered tabletting heavy;
(8) use the tablet machine tabletting, used stamping is No. 10 stampings, and pressure 5～6kg, sheet heavily are 0.3g;
(9) the good tablet of packing punching press, and calculated yield.
Preparation technology's note
Acrivastine, pseudoephedrine hydrochloride are its effective ingredient, and hydroxypropyl emthylcellulose K4M and hydroxypropyl emthylcellulose (100mPa.s) are the framework material of slow releasing tablet, and lactose is a filler.Magnesium stearate and silicon dioxide are lubricant.
For fear of the principal agent photolysis, its operating process should be avoided the strong illumination material.For principal agent is fully dissolved, raw material is crossed 100 mesh sieves, and even in order to make medicament contg, lactose is crossed 100 mesh sieves.
2. prescription screening requirement
This product is a slow releasing tablet, relevant requirements according to Chinese Pharmacopoeia 2010 editions appendix I A and appendix XIXD, detections such as slow releasing tablet uniformity, release are investigated, noted outward appearance, hardness, weight differential, the content of preparation, the ease for operation and the repeatability of technology simultaneously.
3. prescription screening
Prescription screening is carried out in requirement according to 2010 editions tablet general rules of Chinese Pharmacopoeia, and mainly investigating index is release, forms to determine satisfactory prescription.
This experiment is carried out single factor to sustained-release tablet recipe and is investigated under conditions such as stator weight, facility for granulating, tablet machine parameter, temperature and humidity.
Different framework materials is to the influence to the slow releasing tablet release of the influence of slow releasing tablet release and identical slow-release material different amounts
The different framework material of table 1 is to the influence of compound recipe acrivastine slow releasing tablet release
After more than pressing the recipe quantity mixing, be that binding agent 20 mesh sieves are granulated, dash for No. 10 with 70% ethanol, hardness 5.5kg, the heavy 0.3g/ sheet of sheet is surveyed its release by the quality standard method.
Conclusion: from above release result, as can be seen HPMCK4M40mg HPMC100mPa.s) release the best during 20mg, and compressibility is fine.
Different binding agents are to the influence of compound recipe acrivastine slow releasing tablet release
The different binding agents of table 2 are to the influence of compound recipe acrivastine slow releasing tablet release
After more than pressing the recipe quantity mixing, granulate with different binding agent 20 mesh sieves, dash for No. 10, sheet weight 0.3g surveys its release by the quality standard method.
Conclusion: by the release result, 70% alcohol granulation discharges best as can be seen.
Different filleies are to the influence of compound recipe acrivastine slow releasing tablet release
The different filleies of table 3 are to the influence of compound recipe acrivastine slow releasing tablet release
After more than pressing the recipe quantity mixing, granulate with same binder 20 mesh sieves, dash for No. 10, sheet weight 0.3g surveys its release by the quality standard method.
Conclusion: two kinds of filleies compare, and lactose is obviously fast than microcrystalline Cellulose to the release of principal agent, and in the release scope of setting, so select lactose to do filler.
Brief summary: according to above experiment, more than the prescription tentatively draft slow-release material be HPMCK4M40mg HPMC100mPa.s) 20mg, filler is a lactose, 70% alcohol granulation.
The investigation of Different Preparation
Method one: above prescription preparation is all with tabletting behind the direct mixed pelletization of powder;
Method two: with acrivastine crude drug, pseudoephedrine hydrochloride, lactose, cross behind 100 mesh sieves by the abundant mix homogeneously of equivalent incremental method respectively; In above-mentioned blended medicated powder, add hydroxypropyl emthylcellulose K4M and hydroxypropyl emthylcellulose (100mPa.s) mixing, make binding agent, the system soft material with an amount of 70% ethanol; Soft material is passed through the wet grain of 20 mesh sieve systems; Granule is put into baking oven, 55-65 ℃ after dry 15-20 minute, take out and naturally cool to room temperature; Dried granule is passed through 20 mesh sieve granulate; With granule mix homogeneously behind the magnesium stearate, silicon dioxide and the granulate that take by weighing, tabletting.
The influence of the different preparation methoies of table 4 to discharging
Conclusion: method two obviously is better than method one to the release of principal agent
All can reach requirement with discharging.
The prescription screening brief summary: according to above prescription screening, and by a large amount of previous experiments results as can be known:
(1) dissimilar framework materials have considerable influence to the slow releasing tablet release, with HPMCK4M40mg HPMC100mPa.s) 20mg the best.
(2) different types of binding agent has remarkable difference to the release of slow releasing tablet, and 70% ethanol has facilitation than other binding agent to the release of slow releasing tablet
(3) different filler has remarkable difference to the release of slow releasing tablet.
Tablet hardness is to the influence of drug release
After same prescription adopted different compression force tablettings, the hardness that obtains tablet was respectively 4kg, 5kg, 6kg, the results are shown in Table 7.
The influence that table 7 different hardness discharges compound recipe acrivastine slow releasing tablet
Conclusion: when tablet hardness is 4kg, 5kg, principal agent discharges and is more or less the same during 6kg.Multiple factors such as comprehensive compound recipe acrivastine slow releasing tablet coating, selecting the hardness of slow releasing tablet is 5～6kg.
The craft screening brief summary:
(1) system of selection two pelletizing press sheets
(2) tablet hardness is controlled at 5～6kg
[inspection]
Related substance is with reference to State Food and Drug Administration's related standards, and we have investigated the influence of the sample size of sample to chromatographic peak profile again, and the dirt content test method has been carried out methodological study again.On this basis, my method in the draft of settling the standard is used for the mensuration of compound recipe acrivastine slow releasing tablet related substance.All up to specification on inspection.
Release is with reference to State Food and Drug Administration's standard pertinent regulations, and we have carried out methodological study to assay method again, and to the release homogeneity of grinding sample certainly and rate of release is studied and commercially available product relatively, basically identical.
[assay] on the experimental basis of interference, linearity, precision and the response rate of investigation method, we adopt the content according to high effective liquid chromatography for measuring acrivastine and pseudoephedrine hydrochloride.All up to specification through check.
[study on the stability] stability test is the result show: high temperature does not have obvious influence to the stability of compound recipe acrivastine slow releasing tablet, and high humidity can make the heavy obviously increase of the sheet of this product, and the illumination acrivastine easily decomposes, to photo-labile.Therefore, the holding conditions of this product should be: lucifuge, drying, the shady and cool airtight preservation in place; But the effect duration of accelerated test result's preliminary forecasting this product is 2 years; The result that long term test kept sample 6 months shows that this product is stable, and test is still in process.
6, overall merit
Compound recipe acrivastine slow releasing tablet is that the acrivastine crude drug adds suitable adjuvant, the tablet that the rational technology of warp is made.Through study on the stability and related detection, the quality standard of being formulated (content, character, discriminating, release etc.) can be controlled the quality of medicine well.
Compound recipe acrivastine slow releasing tablet of the present invention, specification is acrivastine 16mg, and pseudoephedrine hydrochloride 120mg this product is useful for seasonal allergic rhinitis, and 2 times on the one, sooner or later respectively once, 24 hours are effectively.
Claims (3)
1. compound recipe acrivastine slow releasing tablet is characterized in that: mass ratio of its each component of prescription raw material is:
Acrivastine: 14-18
Pseudoephedrine hydrochloride: 118-122
Hydroxypropyl emthylcellulose K4M:38-42
Hydroxypropyl emthylcellulose (100mPa.s): 18-22
Lactose: 98-102
Magnesium stearate: 1-3
SiO
2： 1-3
70% ethanol: an amount of.
2. compound recipe acrivastine slow releasing tablet according to claim 1 is characterized in that: the mass ratio of its each component of prescription raw material is:
Acrivastine: 16
Pseudoephedrine hydrochloride: 120
Hydroxypropyl emthylcellulose K4M:40
Hydroxypropyl emthylcellulose (100mPa.s): 20
Lactose: 100
Magnesium stearate: 2
SiO
2： 2
70% ethanol: an amount of.
3. the preparation method of compound recipe acrivastine slow releasing tablet as claimed in claim 1 or 2 is characterized in that: specifically may further comprise the steps:
(1) lucifuge operation takes by weighing each supplementary material by prescription, and is standby;
(2) with acrivastine crude drug, pseudoephedrine hydrochloride, lactose, cross behind 100 mesh sieves by the abundant mix homogeneously of equivalent incremental method respectively;
(3) in above-mentioned blended medicated powder, add hydroxypropyl emthylcellulose K4M and hydroxypropyl emthylcellulose (100mPa.s) mixing, make binding agent, the system soft material with an amount of 70% ethanol;
(4) soft material is passed through the wet grain of 20 mesh sieve systems;
(5) granule is put into baking oven, 55-65 ℃ after dry 15-20 minute, take out and naturally cool to room temperature;
(6) dried granule is passed through 20 mesh sieve granulate;
(7) granule mix homogeneously behind the magnesium stearate that will take by weighing, silicon dioxide and the granulate, detection level is calculated and is answered tabletting heavy;
(8) use the tablet machine tabletting, used stamping is No. 10 stampings, pressure 5～6kg;
(9) the good tablet of packing punching press.
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108125924A (en) * | 2018-03-16 | 2018-06-08 | 重庆华邦制药有限公司 | Acrivastine capsule and preparation method thereof |
| US10874616B2 (en) | 2012-11-15 | 2020-12-29 | Incyte Corporation | Sustained-release dosage forms of ruxolitinib |
| US11045421B2 (en) | 2013-08-07 | 2021-06-29 | Incyte Corporation | Sustained release dosage forms for a JAK1 inhibitor |
| US11214573B2 (en) | 2011-06-20 | 2022-01-04 | Incyte Holdings Corporation | Azetidinyl phenyl, pyridyl or pyrazinyl carboxamide derivatives as JAK inhibitors |
| US11285140B2 (en) | 2010-03-10 | 2022-03-29 | Incyte Corporation | Piperidin-4-yl azetidine derivatives as JAK1 inhibitors |
| US11331320B2 (en) | 2005-12-13 | 2022-05-17 | Incyte Holdings Corporation | Heteroaryl substituted pyrrolo[2,3-b]pyridines and pyrrolo[2,3-b]pyrimidines as Janus kinase inhibitors |
| US11833155B2 (en) | 2020-06-03 | 2023-12-05 | Incyte Corporation | Combination therapy for treatment of myeloproliferative neoplasms |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US11331320B2 (en) | 2005-12-13 | 2022-05-17 | Incyte Holdings Corporation | Heteroaryl substituted pyrrolo[2,3-b]pyridines and pyrrolo[2,3-b]pyrimidines as Janus kinase inhibitors |
| US11744832B2 (en) | 2005-12-13 | 2023-09-05 | Incyte Corporation | Heteroaryl substituted pyrrolo[2,3-b]pyridines and pyrrolo[2,3-b]pyrimidines as Janus kinase inhibitors |
| US11285140B2 (en) | 2010-03-10 | 2022-03-29 | Incyte Corporation | Piperidin-4-yl azetidine derivatives as JAK1 inhibitors |
| US11214573B2 (en) | 2011-06-20 | 2022-01-04 | Incyte Holdings Corporation | Azetidinyl phenyl, pyridyl or pyrazinyl carboxamide derivatives as JAK inhibitors |
| US10874616B2 (en) | 2012-11-15 | 2020-12-29 | Incyte Corporation | Sustained-release dosage forms of ruxolitinib |
| US11337927B2 (en) | 2012-11-15 | 2022-05-24 | Incyte Holdings Corporation | Sustained-release dosage forms of ruxolitinib |
| US11576865B2 (en) | 2012-11-15 | 2023-02-14 | Incyte Corporation | Sustained-release dosage forms of ruxolitinib |
| US11576864B2 (en) | 2012-11-15 | 2023-02-14 | Incyte Corporation | Sustained-release dosage forms of ruxolitinib |
| US11896717B2 (en) | 2012-11-15 | 2024-02-13 | Incyte Holdings Corporation | Sustained-release dosage forms of ruxolitinib |
| US11045421B2 (en) | 2013-08-07 | 2021-06-29 | Incyte Corporation | Sustained release dosage forms for a JAK1 inhibitor |
| CN108125924A (en) * | 2018-03-16 | 2018-06-08 | 重庆华邦制药有限公司 | Acrivastine capsule and preparation method thereof |
| US11833155B2 (en) | 2020-06-03 | 2023-12-05 | Incyte Corporation | Combination therapy for treatment of myeloproliferative neoplasms |
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