CN100482227C - Sustained release compound capsules and its preparation method - Google Patents
Sustained release compound capsules and its preparation method Download PDFInfo
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- CN100482227C CN100482227C CNB2004100256669A CN200410025666A CN100482227C CN 100482227 C CN100482227 C CN 100482227C CN B2004100256669 A CNB2004100256669 A CN B2004100256669A CN 200410025666 A CN200410025666 A CN 200410025666A CN 100482227 C CN100482227 C CN 100482227C
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- Prior art keywords
- desloratadine
- coating
- slow
- plain
- preparation
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- 239000002775 capsule Substances 0.000 title claims abstract description 30
- 238000002360 preparation method Methods 0.000 title claims abstract description 27
- 150000001875 compounds Chemical class 0.000 title claims abstract description 19
- 238000013268 sustained release Methods 0.000 title claims abstract description 15
- 239000012730 sustained-release form Substances 0.000 title claims abstract description 15
- 229960001271 desloratadine Drugs 0.000 claims abstract description 53
- JAUOIFJMECXRGI-UHFFFAOYSA-N Neoclaritin Chemical compound C=1C(Cl)=CC=C2C=1CCC1=CC=CN=C1C2=C1CCNCC1 JAUOIFJMECXRGI-UHFFFAOYSA-N 0.000 claims abstract description 52
- KWGRBVOPPLSCSI-WCBMZHEXSA-N pseudoephedrine Chemical compound CN[C@@H](C)[C@@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WCBMZHEXSA-N 0.000 claims abstract description 18
- KWGRBVOPPLSCSI-UHFFFAOYSA-N d-ephedrine Natural products CNC(C)C(O)C1=CC=CC=C1 KWGRBVOPPLSCSI-UHFFFAOYSA-N 0.000 claims abstract description 17
- 229960003908 pseudoephedrine Drugs 0.000 claims abstract description 17
- 239000002245 particle Substances 0.000 claims abstract description 4
- 238000000576 coating method Methods 0.000 claims description 53
- 239000011248 coating agent Substances 0.000 claims description 52
- CAVQBDOACNULDN-NRCOEFLKSA-N (1s,2s)-2-(methylamino)-1-phenylpropan-1-ol;sulfuric acid Chemical compound OS(O)(=O)=O.CN[C@@H](C)[C@@H](O)C1=CC=CC=C1.CN[C@@H](C)[C@@H](O)C1=CC=CC=C1 CAVQBDOACNULDN-NRCOEFLKSA-N 0.000 claims description 18
- 229960004159 pseudoephedrine sulfate Drugs 0.000 claims description 18
- 239000012530 fluid Substances 0.000 claims description 16
- 239000008187 granular material Substances 0.000 claims description 13
- 230000003578 releasing effect Effects 0.000 claims description 13
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 12
- 239000000463 material Substances 0.000 claims description 11
- 238000005516 engineering process Methods 0.000 claims description 10
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 10
- 229920002472 Starch Polymers 0.000 claims description 8
- 239000006187 pill Substances 0.000 claims description 8
- 239000008107 starch Substances 0.000 claims description 8
- 235000019698 starch Nutrition 0.000 claims description 8
- 239000007921 spray Substances 0.000 claims description 7
- 239000013530 defoamer Substances 0.000 claims description 6
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 6
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 6
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 5
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical group [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 claims description 5
- 235000019700 dicalcium phosphate Nutrition 0.000 claims description 5
- 238000001035 drying Methods 0.000 claims description 5
- 235000019359 magnesium stearate Nutrition 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- 239000011734 sodium Substances 0.000 claims description 5
- 229910052708 sodium Inorganic materials 0.000 claims description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 4
- 239000011230 binding agent Substances 0.000 claims description 4
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 4
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 4
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 4
- 229960003943 hypromellose Drugs 0.000 claims description 4
- 238000000034 method Methods 0.000 claims description 4
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 claims description 4
- 239000004014 plasticizer Substances 0.000 claims description 4
- 239000003223 protective agent Substances 0.000 claims description 4
- 239000000741 silica gel Substances 0.000 claims description 4
- 229910002027 silica gel Inorganic materials 0.000 claims description 4
- 238000005507 spraying Methods 0.000 claims description 4
- 239000001856 Ethyl cellulose Substances 0.000 claims description 3
- 239000002671 adjuvant Substances 0.000 claims description 3
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 3
- 229920001249 ethyl cellulose Polymers 0.000 claims description 3
- 235000019325 ethyl cellulose Nutrition 0.000 claims description 3
- -1 granulation Substances 0.000 claims description 3
- 239000007779 soft material Substances 0.000 claims description 3
- 235000021355 Stearic acid Nutrition 0.000 claims description 2
- 229920001615 Tragacanth Polymers 0.000 claims description 2
- 239000000305 astragalus gummifer gum Substances 0.000 claims description 2
- 239000004203 carnauba wax Substances 0.000 claims description 2
- 239000007766 cera flava Substances 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 229940060534 desloratadine 2.5 mg Drugs 0.000 claims description 2
- 229940029077 desloratadine 5 mg Drugs 0.000 claims description 2
- 229960004667 ethyl cellulose Drugs 0.000 claims description 2
- 238000005469 granulation Methods 0.000 claims description 2
- 230000003179 granulation Effects 0.000 claims description 2
- 239000000314 lubricant Substances 0.000 claims description 2
- 229920000609 methyl cellulose Polymers 0.000 claims description 2
- 239000001923 methylcellulose Substances 0.000 claims description 2
- 229960002900 methylcellulose Drugs 0.000 claims description 2
- 235000010981 methylcellulose Nutrition 0.000 claims description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 2
- 239000003361 porogen Substances 0.000 claims description 2
- 239000008117 stearic acid Substances 0.000 claims description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 239000003814 drug Substances 0.000 description 6
- 239000000203 mixture Substances 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical compound CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 239000001069 triethyl citrate Substances 0.000 description 4
- VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 description 4
- 235000013769 triethyl citrate Nutrition 0.000 description 4
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 2
- 239000004925 Acrylic resin Substances 0.000 description 2
- 229920000178 Acrylic resin Polymers 0.000 description 2
- 208000035285 Allergic Seasonal Rhinitis Diseases 0.000 description 2
- 206010028735 Nasal congestion Diseases 0.000 description 2
- 206010048908 Seasonal allergy Diseases 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 230000001476 alcoholic effect Effects 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 229920001477 hydrophilic polymer Polymers 0.000 description 2
- 229960003088 loratadine Drugs 0.000 description 2
- 235000010603 pastilles Nutrition 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 229960004793 sucrose Drugs 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229920003081 Povidone K 30 Polymers 0.000 description 1
- 206010039085 Rhinitis allergic 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
- 201000010105 allergic rhinitis Diseases 0.000 description 1
- CKMXBZGNNVIXHC-UHFFFAOYSA-L ammonium magnesium phosphate hexahydrate Chemical compound [NH4+].O.O.O.O.O.O.[Mg+2].[O-]P([O-])([O-])=O CKMXBZGNNVIXHC-UHFFFAOYSA-L 0.000 description 1
- 230000001387 anti-histamine Effects 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 239000004148 curcumin Substances 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 238000009501 film coating Methods 0.000 description 1
- 239000007888 film coating Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
- 230000004968 inflammatory condition Effects 0.000 description 1
- JCCNYMKQOSZNPW-UHFFFAOYSA-N loratadine Chemical compound C1CN(C(=O)OCC)CCC1=C1C2=NC=CC=C2CCC2=CC(Cl)=CC=C21 JCCNYMKQOSZNPW-UHFFFAOYSA-N 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 201000009240 nasopharyngitis Diseases 0.000 description 1
- 229960005489 paracetamol Drugs 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229940093429 polyethylene glycol 6000 Drugs 0.000 description 1
- 229940022361 pseudoephedrine sulfate 120 mg Drugs 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 229910052567 struvite Inorganic materials 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 238000009492 tablet coating Methods 0.000 description 1
- 239000002700 tablet coating Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
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- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a sustained release compound capsules and its preparation method, wherein each capsule comprises a desloratadine tablet and a plurality of pseudo ephedrine slow release particles, the active components include desloratadine 2.5mg-5mg, pseudo ephedrine 120mg-240mg. The compound slow release capsule can increase the biological availability and compliableness for the patients.
Description
Technical field
The present invention relates to a kind of dosage form of medicine, relate in particular to a kind of compound sustained release capsules and preparation method thereof.
Background technology
Treatment at present show with the patient of allergia and/or relevant sign of inflammatory conditions (as common cold) and symptom and with skin or on lower respiratory tract allergia and/or struvite pathological changes, for example hand over answering property rhinitis, the pollinosis sign relevant with nasal congestion upper respiratory disease, allergic rhinitis and nasal congestion and the patient of symptom, the salt that generally adopts Desloratadine and pseudoephedrine or its to have the pharmacologically active effect refers to the pseudoephedrine sulfate therapeutic alliance.But present dosage form needs more than a day time to take, and causes patient's compliance relatively poor, and causes easily and miss phenomenon.Because the gap between the half-life of pseudoephedrine and the half-life of Desloratadine is great disparity relatively.Simply, then can can't reach and keep an effective blood drug level simultaneously, and can not reach satisfactory therapeutic effects because of both with the compound preparation of pseudoephedrine and Desloratadine composition.
Desloratadine, also be referred to as many times be-remove ethoxycarbonyl loratadine (descarbethoxyloratadine), be effective degradation material of loratadine, be used for the non-sedative antihistamine medicine that resistance is answered the disease reactant, in U.S. Pat 4659716, describe as a kind of.U.S. Pat 6100274 discloses the compositions that contains Desloratadine.U.S. Pat 5595997 discloses the method and formulation that uses Desloratadine treatment pollinosis symptom, Desloratadine, after oral administration absorbs, at 3 by carboxylated and generate metabolite 3-hydroxyl Desloratadine.
U.S. Pat 4990535 and 5100675 discloses a kind of one day administered twice sustained release coating sheet, and wherein this tablet coating contains Desloratadine.Hydrophilic polymer and Polyethylene Glycol, and the core of this tablet contains acetaminophen, isoephedrine or its salt, expandable hydrophilic polymer and pharmaceutically acceptable excipient.
U.S. Pat 5314697 discloses a kind of tablet of slow release, the substrate heart that contains pseudoephedrine sulfate is arranged and exist in Desloratadine in the clothing film.
Schering Corp discloses a kind of slow-release solid oral formulations of film coating in Chinese patents CN 00137300, the pseudoephedrine sulfate that has comprised slow-released part in ball core substrate is loaded with the Desloratadine of required dosage in the clothing film on the surface of piller.
The tablet that prior art did not disclose the micropill of the pseudoephedrine that will have slow releasing function that is administered once every day of the present invention and contained Desloratadine is filled in the preparation of forming compound recipe among the same capsule jointly.
Summary of the invention
The object of the present invention is to provide a kind of compliance good, have slow-release function, can make Desloratadine and pseudoephedrine reach and keep the compound capsule of effective blood drug concentration simultaneously.
Another object of the present invention is to provide a kind of preparation method of compound capsule.
A kind of compound sustained release capsules of the present invention, every capsules is made up of a slice Desloratadine sheet and some pseudoephedrinees or its slow-releasing granules with salt of pharmacologically active, wherein contains his 2.5mg～5mg of active component ground chlorine thunder, pseudoephedrine or it has the salt 120mg～240mg of pharmacologically active; Described Desloratadine sheet is made up of plain sheet of Desloratadine and plain coating tablets, wherein the plain sheet of Desloratadine comprises Desloratadine, Desloratadine protective agent, binding agent, lubricant and fluidizer, and plain coating tablets comprises filmogen, film modifying agent, antiplastering aid and defoamer; Described slow-releasing granules is the micropill of film-controlled slow-release or micropill or the film-controlled slow-release and the bonded micropill of skeleton slow release of skeleton slow release.
Wherein the Desloratadine protective agent is the adjuvant that pharmacy is accepted that can be that has alkalescence a little.
The micropill of film-controlled slow-release is made up of plain ball, ground floor coating and second layer coating, plain ball comprises that pseudoephedrine or its have the salt of pharmacologically active, excipient and the blank pill heart, the ground floor coating comprises coating material, plasticizer, defoamer and the porogen with slow releasing function, and second layer coating comprises coating material, plasticizer and defoamer.
The micropill of skeleton slow release is made up of pseudoephedrine sulfate, excipient, binding agent and skeleton slow-release material.
The skeleton slow-release material is one or more in Cera Flava, Brazil wax, stearic acid, octadecanol, hypromellose, ethyl cellulose, methylcellulose, tragacanth gum, the Lac.
Described coating material is the aqueous dispersion of ethyl cellulose, all kinds of acrylic resin, Lac, Aquacoat, all kinds of acrylic resins.
Desloratadine sheet in the preferred every capsules of the present invention contains Desloratadine 5mg, starch 27mg, calcium hydrogen phosphate 9mg, polyvidone 1mg, carboxymethyl starch sodium 9mg, micropowder silica gel 0.5mg, magnesium stearate 0.5mg; The pseudoephedrine sulfate that contains 240mg in the slow-releasing granules.
The present invention also discloses a kind of preparation method of compound sustained release capsules, comprise that the preparation of Desloratadine sheet and pseudoephedrine or its have the preparation of slow-releasing granules of the salt of pharmacologically active, then with the Desloratadine sheet that obtains with slow release is particles filled obtains in capsule shells.
The preparation of Desloratadine sheet comprises:
(1), the preparation of the plain sheet of Desloratadine: Desloratadine and other adjuvants are sieved, and mixed then soft material, granulation, granulate, tabletting obtain;
(2), plain coating tablets: the plain sheet of the Desloratadine that obtains is made with the coating solution coating.
The preparation of slow-releasing granules comprises:
(1) preparation of plain ball: at first preparation contains pseudoephedrine or it has the solution of the salt of pharmacologically active, gets celphere then and is placed on and adopts the side pressure spray process above-mentioned solution to be loaded into the surface of celphere in the fluid bed;
(2) ground floor coating: at first prepare coating solution, get plain ball then, with the technology of fluid bed side spray coating solution is sprayed to plain ball surface and carries out coating, drying obtains again;
(3) second layer coating: at first prepare coating solution, get the micropill that the ground floor coating obtains then, with the technology of fluid bed side spray coating solution is sprayed to above-mentioned micropill surface and carries out coating, drying obtains again;
(4) the clothing film solidifies: the micropill that obtains in the step (3) is cured.
Compound sustained release capsules of the present invention, comprise the slow-release micro-pill of forming by pseudoephedrine or its salt in its content simultaneously and can guarantee that the tablet that discharged Desloratadine once in a day is constituted with pharmacologically active, this slow-release micro-pill can be kept the releasing effect more than 12 hours, can arrive and keep an effective blood drug level with Desloratadine simultaneously, improved bioavailability and patient's compliance, and taken once in one day and get final product.
The specific embodiment
Embodiment: 10000 compound sustained release capsules of present embodiment preparation
1, the preparation of the plain sheet of Desloratadine:
Plain tablet recipe: Desloratadine 25g starch 270g
Calcium hydrogen phosphate 90g polyvidone 10g
Carboxymethylstach sodium 90g micropowder silica gel 5g
Magnesium stearate 5g
A, Desloratadine, starch are crossed 120 mesh sieves, it is standby that calcium hydrogen phosphate is crossed 100 mesh sieves;
Polyvidone (70% alcoholic solution) solution of b, preparation 10% takes by weighing the carboxymethylstach sodium mix homogeneously of Desloratadine, starch phosphate hydrogen calcium and 2/3 amount;
C, mixed material is made even soft material, granulate through 30 mesh sieves with 10% 30 POVIDONE K 30 BP/USP, 30 alcoholic solutions;
D, 55 ℃ of oven dry through 30 mesh sieve granulate, add remaining carboxymethyl starch sodium, micropowder silica gel, magnesium stearate, mixing;
E, according to the in flakes heavy 50mg tablet of the method for routine compacting, hardness 3kg/ sheet.
2, the coating of Desloratadine tablet:
Coating fluid prescription: 10000 of plain sheets
Methacrylic acid aminoalkyl ester copolymer E100 12.5g
Magnesium stearate 5g polyethylene glycol 6000 1g
Water 2g ethanol 160g
Configure after the coating solution according to coating fluid prescription, adopt conventional coating method to carry out coating and obtain the Desloratadine sheet.
3, the preparation of the plain ball of pseudoephedrine sulfate:
Plain ball prescription: cane sugar type medicinal fine pellet core 600.0g
Pseudoephedrine sulfate 1000.0g polyvidone 60.0g
Hypromellose 10.0g 75% ethanol 1400ml
A, the pseudoephedrine sulfate of getting recipe quantity, polyvidone, hypromellose, the dissolve with ethanol with 75%, the solution of pastille;
B, the sucrose ball heart of getting recipe quantity are placed on the surface that the technology that adopts the side spray in the fluid bed is loaded into the solution of pastille in the blank pill heart; (45 ℃ of inlet temperature, air quantity 24HZ, atomizing pressure 3.0kg, flow velocity 10 → 15rpm, rotary speed 10 → 14 → 15HZ)
The plain ball that has loaded medicine is dried to moisture content less than 2% with the capable drying of fluid bed top spirt (50 ℃ of inlet temperature, air quantity 21.6HZ).
4, the ground floor coating of the plain ball of pseudoephedrine sulfate:
Coating fluid prescription:
The plain ball 1670g of pseudoephedrine sulfate
Aquacoat Aquacoat ECD 560ml
Triethyl citrate 25g
Pure water 560ml
Technology: a, the Aquacoat Aquacoat that gets recipe quantity add one times of amount of water and dilute, and add the triethyl citrate of recipe quantity, stir 3 hours;
B, get the plain ball of the pseudoephedrine sulfate of recipe quantity, the coating operation is carried out on the surface that coating solution is sprayed to plain ball with the technology of fluid bed side spray.(40 ℃ of air quantity 23HZ of air quantity 25HZ inlet temperature atomizing pressure 3.0kg flow velocity 6rpm rotary speed 14HZ)
The micropill that c will wrap clothing pushes up dry 0.5 hour (50 ℃ of inlet temperature, the air quantity 22HZ) of spray in fluid bed.
5, the second layer coating of pseudoephedrine sulfate slow-release micro-pill:
Coating fluid prescription: ground floor coating pseudoephedrine sulfate micropill 1835g
Aquacoat Aquacoat ECD 560ml
Triethyl citrate 25g
Pure water 560ml
Pseudoephedrine sulfate 200mg
Technology: a, the Aquacoat Aquacoat that gets recipe quantity add one times of amount of water and dilute, and the back that stirs adds pseudoephedrine sulfate, continues stirring and dissolving, adds the triethyl citrate of recipe quantity, stirs 3 hours;
B, get the plain ball of the pseudoephedrine sulfate of recipe quantity, coating operation (40 ℃ of air quantity 23HZ of air quantity 25HZ inlet temperature atomizing pressure 3.0kg flow velocity 6rpm rotary speed 14HZ) is carried out on the surface that coating solution is sprayed to plain ball with the technology of fluid bed side spray;
C, the micropill that will wrap clothing push up dry 0.5 hour (50 ℃ of inlet temperature, the air quantity 22HZ) of spray in fluid bed.
6, the clothing film solidifies:
The micropill that obtains at last solidified under 60 ℃ of conditions obtained the pseudoephedrine slow-release micro-pill in 24 hours.
7, filled capsules:
The Desloratadine sheet and the pseudoephedrine slow-release micro-pill that obtain are filled in the capsule shells simultaneously, make and contain Desloratadine 2.5mg, pseudoephedrine sulfate 120mg in every capsules.
Claims (6)
1. compound sustained release capsules, it is characterized in that every capsules is filled in the capsule shells by a slice Desloratadine sheet and some pseudoephedrinees or its slow-releasing granules with salt of pharmacologically active forms, and wherein contains active component Desloratadine 2.5mg～5mg, pseudoephedrine or it has the salt 120mg～240mg of pharmacologically active; Described Desloratadine sheet is made up of plain sheet of Desloratadine and plain coating tablets, wherein the plain sheet of Desloratadine comprises Desloratadine, Desloratadine protective agent, binding agent, lubricant and fluidizer, and plain coating tablets comprises filmogen, film modifying agent, antiplastering aid and defoamer; Described slow-releasing granules is the micropill of film-controlled slow-release or micropill or the film-controlled slow-release and the bonded micropill of skeleton slow release of skeleton slow release; Described Desloratadine protective agent is a calcium hydrogen phosphate.
2. compound sustained release capsules according to claim 1, the micropill that it is characterized in that film-controlled slow-release is made up of plain ball, ground floor coating and second layer coating, plain ball comprises that pseudoephedrine or its have the salt of pharmacologically active, excipient and the blank pill heart, the ground floor coating comprises coating material, plasticizer, defoamer and the porogen with slow releasing function, and second layer coating comprises coating material, plasticizer and defoamer.
3. compound sustained release capsules according to claim 1 is characterized in that the micropill of skeleton slow release is made up of pseudoephedrine sulfate, excipient, binding agent and skeleton slow-release material.
4. compound sustained release capsules according to claim 3 is characterized in that the skeleton slow-release material is one or more in Cera Flava, Brazil wax, stearic acid, octadecanol, hypromellose, ethyl cellulose, methylcellulose, tragacanth gum, the Lac.
5. compound sustained release capsules according to claim 1 is characterized in that the Desloratadine sheet in every capsules contains Desloratadine 5mg, starch 27mg, calcium hydrogen phosphate 9mg, polyvidone 1mg, carboxymethyl starch sodium 9mg, micropowder silica gel 0.5mg, magnesium stearate 0.5mg; The pseudoephedrine sulfate that contains 240mg in the slow-releasing granules.
6. the preparation method of compound sustained release capsules according to claim 1 is characterized in that comprising the preparation and the particulate preparation of slow release of Desloratadine sheet, then with the Desloratadine sheet that obtains with slow release is particles filled obtains in capsule shells; Wherein, the preparation of Desloratadine sheet may further comprise the steps:
(1) preparation of the plain sheet of Desloratadine: Desloratadine and other adjuvants are sieved, and mixed then soft material, granulation, granulate, tabletting obtain;
(2) plain coating tablets: the plain sheet of the Desloratadine that obtains is made with the coating solution coating, then with the Desloratadine sheet that obtains with slow release is particles filled obtains in capsule shells;
The preparation of slow-releasing granules may further comprise the steps:
(1) preparation of plain ball: at first preparation contains pseudoephedrine or it has the solution of the salt of pharmacologically active, gets celphere then and is placed on and adopts the side pressure spray process above-mentioned solution to be loaded into the surface of celphere in the fluid bed;
(2) ground floor coating: at first prepare coating solution, get plain ball then, with the technology of fluid bed side spray coating solution is sprayed to plain ball surface and carries out coating, drying obtains again;
(3) second layer coating: at first prepare coating solution, get the micropill that the ground floor coating obtains then, with the technology of fluid bed side spray coating solution is sprayed to above-mentioned micropill surface and carries out coating, drying obtains again;
(4) the clothing film solidifies: the micropill that obtains in the step (3) is cured.
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| Application Number | Priority Date | Filing Date | Title |
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| CNB2004100256669A CN100482227C (en) | 2004-07-01 | 2004-07-01 | Sustained release compound capsules and its preparation method |
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| Application Number | Priority Date | Filing Date | Title |
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| CNB2004100256669A CN100482227C (en) | 2004-07-01 | 2004-07-01 | Sustained release compound capsules and its preparation method |
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| CN1593413A CN1593413A (en) | 2005-03-16 |
| CN100482227C true CN100482227C (en) | 2009-04-29 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101849902B (en) * | 2010-06-03 | 2012-06-06 | 浙江华海药业股份有限公司 | Preparation method of solid pharmaceutical composition containing desloratadine |
| CN105535144B (en) * | 2016-01-28 | 2019-04-16 | 南方医科大学 | A kind of capsule for treating allergic rhinitis |
| CN113230235B (en) * | 2021-04-15 | 2022-11-11 | 海南普利制药股份有限公司 | Compound sustained-release capsule containing desloratadine and preparation method thereof |
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2004
- 2004-07-01 CN CNB2004100256669A patent/CN100482227C/en not_active Expired - Lifetime
Non-Patent Citations (2)
| Title |
|---|
| HPLC法同时测定复方氯雷他定缓释胶囊中两组分含量. 黄薇薇等.儿科药学杂志，第8卷第4期. 2002 |
| HPLC法同时测定复方氯雷他定缓释胶囊中两组分含量. 黄薇薇等.儿科药学杂志，第8卷第4期. 2002 * |
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| CN1593413A (en) | 2005-03-16 |
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Address after: 571127 Guilin economic and Technological Development Zone, Meilan District, Hainan, Haikou Patentee after: HAINAN POLY PHARM. Co.,Ltd. Patentee after: ZHEJIANG POLY PHARMACEUTICAL Co.,Ltd. Patentee after: HANGZHOU SHARPLY PHARM R&D INSTIT. Co.,Ltd. Address before: 571127 Guilin economic and Technological Development Zone, Meilan District, Hainan, Haikou Patentee before: Hainan Poly Pharm Co.,Ltd. Patentee before: Zhejiang Ruida Pharm Co.,Ltd. Patentee before: HANGZHOU SHARPLY PHARM R&D INSTIT. Co.,Ltd. |
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