Drug delivery system containing weakly basic selective serotonin 5-ht3 blocking agent and organic acid 机翻标题: 暂无翻译,请尝试点击翻译按钮。

源语言标题
(JP2016014048) 弱​塩基​性​選択​性​セロトニン​5−H​T​3​遮断​剤​および​有機​酸​を​含む​薬物​送達​系
公开号/公开日
JP2016014048 A 2016-01-28 [JP2016014048] / 2016-01-28
申请号/申请日
2015JP-0188001 / 2015-09-25
发明人
VANKATESH GOPI M;LAI JIN-WANG;VYAS NEHAL H;
申请人
ADARE PHARMACEUTICALS;
主分类号
IPC分类号
A61K-009/14A61K-009/20A61K-031/4178A61K-045/00A61K-047/10A61K-047/12A61K-047/14A61K-047/26A61K-047/32A61K-047/34A61K-047/38A61K-047/46
摘要
(JP2016014048) PROBLEM TO BE SOLVED: To provide a new pharmaceutical multiparticle dosage form.SOLUTION: A pharmaceutical dosage form such as a capsule, a conventional tablet or orally disintegrating tablet capable of delivering a weakly basic nitrogen (N)-containing selective serotonin 5-HTblocking agent having a pKa in the range of from about 5 to 14 and a solubility of about 200 μg/mL or less at pH 6.8 into the body in a sustained-released fashion, suitable for a once-daily dosing regimen, comprises at least one organic acid which solubilizes the weakly basic selective serotonin 5-HTblocking agent prior to releasing it into the hostile intestinal environment where the blocking agent is practically insoluble.  The unit dosage form may be composed of a multitude of multicoated particulates (i.e., immediate-release beads, sustained-release beads and/or one or more timed pulsatile-release bead populations) and is designed in such a way that the weakly basic blocking agent and the organic acid do not come into close contact during processing and/or storage thereby avoiding in-situ formation of acid addition compounds while ensuring that the acid is not depleted prior to completion of the drug release.
机翻摘要
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地址
代理人
代理机构
;
优先权号
2006US-60762750 2006-01-27
主权利要求
(JP2016014048)  1. The immediately discharge (IR) beads and the controlled release characteristic (SR) beads of the weak basic medicine, and/or being the medicine multi particle medicine shapes which include the group of one or more of the time limit pulse type discharge (TPR) beads, the aforementioned weak basic medicine, as a nitrogen (N) content selective [serotonin] 5-HT3 cutoff medicine and the melting medicine which possess the solubility below approximately 200 .micro. g/mL with pKa and pH6.8 inside the range of approximately 5-14 one to include approved possible organic acid at least pharmacy, as for the aforementioned weak basic active ingredient and the aforementioned organic acid, at the time of while producing or keeping in solid stateThere are no times when it contacts mutually, when liquating testing with the stripping method (first 2 hours in 0.1N HCl, continuously test in the buffer with pH6.8) of the American pharmaceutical codex (USP) where because of this, in situ formation of the acid addition compound is evaded, uses 2 gradual liquation medium, to completion of the aforementioned medicine discharge from medicine shape the medicine multi particle medicine shapes where the aforementioned organic acid is not depleted. 2. The ratio for the solubility with pH6.8 of the reaching suitable highest dosage quantity of the aforementioned weak basic medicine is approximately 100 or more, at least the aforementioned weak basic medicine is made to solubilize before the discharging to the intestinal tract environment whose one approved possible organic acid is unsuitable pharmacy, the aforementioned weak basic medicine is insolubility substantially, the aforementioned medicine shape with the patient who needs this kind of medication vis-a-vis the dosage plan of 1 day 1 time ideal target medicine movement study profile after the prescribing is shown in 24 hours, in claim 1 medicine multi particle medicine shapes of statement. 3. A) Outside the aforementioned TPR beads, were applied on the aforementioned SR beads, including the non- water soluble polymer with combination with the intestinal soluble polymer delay time coating is included, coating outside the description above offers the delay time of approximately 2- approximately 7 hours before the starting the medicine discharge, b) The aforementioned SR beads, include the SR (barrier) coating which surrounds the IR beads, the aforementioned SR coating, independently or includes the non- water soluble polymer with combination with the water soluble pore formation characteristic polymer, the aforementioned SR coating offers controlled release characteristic profile, c) The aforementioned IR beads, at least implication one which was applied to the SR coating organic acid core particle weak basic medicine, d) Inside the aforementioned SR coating organic acid core surrounds the organic acid core particle, barrier coating is included, barrier coating inside the description above, independently or includes the non- water soluble polymer with combination with the water soluble pore formation characteristic polymer, at the same time, offers controlled release characteristic profile, e) The aforementioned organic acid core particle one which functioning is done includes approved possible organic acid at least pharmacy as a melting medicine of the aforementioned weak basic medicine, in claim 1 medicine multi particle medicine shapes of statement. 4. 1) The collapse medicine and sugar alcohol or the saccharide which possess the mean diameter of each approximately 30 .micro.m or less or the divination dissolved fine granule which possesses the mean diameter of 400 .micro.m or less where these combinations are included, furthermore to include, the collapse lock inside the aforementioned buccal cavity, contacting with the saliva inside the buccal cavity and collapsing within approximately 60 seconds it becomes the multiplex coating beads, in claim 1 of form of the collapse lock (ODT) inside the buccal cavity medicine multi particle medicine shapes of statement. 5. The aforementioned TPR beads barrier (SR) coating are not included on the aforementioned IR beads, because of this it becomes possible to unsuitable intestinal tract environment to make the solubilization medicine discharge, the said medicine as been ideal with the patient who needs this kind of medication vis-a-vis the dosage plan of 1 day 1 time insolubility, after the oral administration substantially is, in claim 3 medicine multi particle medicine shapes of statement. 6. At least, the IR beads group, the 1st TPR beads group, and the SR beads group or to include the 2nd TPR beads group, with the IR beads group and ratio of the 1st TPR beads group and the SR beads or the 2nd TPR beads group approximately 10:90: 0- approximately 40:10: It changes with 50, in claim 1 medicine multi particle medicine shapes of statement. 7. The aforementioned weak basic nitrogen (N) content selective [serotonin] 5-HT3 cutoff medicine, has the solubility under 100 .micro. g/mL with pKa7.4 and pH6.8, [ondansetoron] which is chemotherapy or the *** air which it is related after the surgical operating and the selective 5-HT3 receptor antagonist which is adapted to the prevention of vomiting condition or it is that pharmacy approved possible salt, in claim 1 medicine multi particle medicine shapes of statement. 8. The aforementioned organic acid, is selected from the group which consists of citric acid, fumaric acid, malic acid, maleic acid, tartaric acid, succinic acid, oxalic acid, aspartic acid, glutamic acid, and these blends, in claim 1 medicine multi particle medicine shapes of statement. 9. Weight ratio with the weak basic medicine and organic acid approximately 5:1-1: It changes with 10, offers ideal target medicine movement study profile to the dosage plan of 1 day 1 time, in claim 1 medicine multi particle medicine shapes of statement. 10. The aforementioned organic acid core particle: i) Organic acid crystal, II) The inactive particle, or III) organic acid which coating is done, the polymer binder and diluent/the bulking agent are contained with organic acid and the polymer binder, the pellet which is manufactured by revolution granulation, granule globose conversion, extrusion molding globose conversion or granulation compression or the minute tablet is included, in claim 3 medicine multi particle medicine shapes of statement. 11. In the aforementioned particle core, independently or approximately 9:1-5 of the water soluble polymer: The barrier (SR) coating which includes the non- water soluble polymer with combination at ratio of 5 is offered, the aforementioned barrier coating, approximately 1.5%-20 weight % is applied with weight increase with the weight of the beads which coating are done as a standard, in claim 3 medicine multi particle medicine shapes of statement. 12. The aforementioned particle barrier coating, the ethyl cellulose, cellulose acetate, cellulose acetate butyrate, poly- vinyl acetate and neutral methacrylic acid - includes the non- water soluble polymer which is selected from methyl methacrylate copolymer, and the group which consists of these blends, in claim 11 medicine multi particle medicine shapes of statement. 13. The methyl cellulose, the hydroxypropyl methyl cellulose and the hydroxypropyl cellulose, the barrier coating which includes the non- water soluble polymer with combination with the water soluble polymer which is selected from poly- vinyl pyrolidone, polyethylene glycol, and the group which consists of these blends is offered to the aforementioned particle core, in claim 11 medicine multi particle medicine shapes of statement. 14. The aforementioned delay time coating, non- water soluble polymer, the respective approximately 9:1-1 of intestinal soluble polymer: With combination at ratio of 3, approximately 10%-60 weight % it includes with weight increase with the weight of the TPR beads as a standard, in claim 3 medicine multi particle medicine shapes of statement. 15. The aforementioned delay time coating, cellulose acetate phthalate and hydroxypropyl methyl cellulose phthalate, [hidorokishipuropirumechiruserurosukushineto], poly- vinyl acetate phthalate and pH sensitivity methacrylic acid - methyl methacrylate copolymer, includes the non- water soluble polymer with combination with the intestinal soluble polymer which is selected from the shellac, these derivatives, and the group which consists of these blends, in claim 14 medicine multi particle medicine shapes of statement. 16. At least one of the inside barrier coating and outer part delay time coating, the triacetin, citric acid tributyl and citric acid triethyl, [kuen] asechirutori - [n]-buchiru, diethyl phthalate, the dibutyl sebacate, polyethylene glycol and polypropylene glycol, the castor oil, includes the plasticizer which is selected from acetylation mono glyceride and the group which consists of [jiguriserido], and these blends, in claim 3 medicine multi particle medicine shapes of statement. 17. The aforementioned IR beads, offer the filling up dosage quantity due to the fact that approximately 50% or more of the active ingredient which within rear 1 hours of oral administration of medicine shape is contained in the aforementioned IR beads discharges, in claim 3 medicine multi particle medicine shapes of statement. 18. When the aforementioned IR beads, it is installed, as the IR part of medicine shape the aforementioned weak basic medicine and the polymer binder which it is laminated are converted to the inactive core are included, in claim 3 medicine multi particle medicine shapes of statement. 19. The aforementioned weak basic medicine [ondansetoron] or that includes the approved possible salt pharmacy, each TPR beads group, in the delay time coating of the non- water soluble ethyl cellulose and intestinal soluble hydroxypropyl methyl cellulose phthalate at ratio of approximately 9:1- approximately 1:3, includes the controlled release characteristic coating fumaric acid core which coating is done with weight increase of 50% or less, the case of oral administration of medicine shape, specified delay time, continuously shows the discharge feature which differs, in claim 1 medicine multi particle medicine shapes of statement. 20. The collapse lock inside the aforementioned buccal cavity, the IR beads group and the SR beads group which the sense of taste mask are done, and/or one of the hydrochloric acid [ondansetoron] two hydrates or includes two TPR beads groups, each SR or the TPR beads group which includes the controlled release characteristic coating fumaric acid core collapses easily in the buccal cavity, the multiplex coating beads it is smooth and forming the suspensoid whose swallowing is easy, it offers ideal target medicine movement study profile with the patient who needs this kind of medication vis-a-vis the dosage plan of 1 day 1 time, in claim 1 medicine multi particle medicine shapes of statement. 21. Approximately being manufacturing method of the multi particle medicine shapes which at least include one pharmacy approved possible organic acid as a weak basic nitrogen (N) content selective [serotonin] 5-HT3 cutoff medicine and the melting medicine which possess the ratio of the reaching suitable highest dosage quantity for the solubility (solubility) of 200 .micro. g/mL or less, and the solubility with pH6.8 of approximately 100 or more with pKa and pH6.8 of the range of the 5-14: a) The process which manufactures the organic acid core, b) In the SR coating which includes the non- water soluble polymer with combination with the water soluble polymer or the intestinal soluble polymer at ratio of the independently or approximately 95:5- approximately 50:50, coating doing the aforementioned organic acid core, with weight increase of approximately 20% or less, the process which manufactures the SR coating organic acid core by offering controlled release characteristic profile, c) The process which manufactures the IR (immediately discharge) beads by applying the protective seal coating with the water soluble polymer the aforementioned weak basicity or by that pharmacy the approved possible salt, from the polymer binder solution laminating converts to the aforementioned SR coating organic acid core, and with option, d) By applying with weight increase of approximately 1.5%-20% with the dry weight of the beads which barrier (SR) coating of the non- water soluble polymer with combination with the water soluble polymer at ratio of the independently the process which manufactures the SR beads or approximately 95:5- approximately 50:50, coating are done, e) Approximately 9:1-1: Outside at ratio of 3 including the non- water soluble polymer with combination with the intestinal soluble polymer, the process which manufactures the TPR beads approximately 10%-60 of the beads which delay time coating, coating are done weight % by applying with weight increase, and f) The IR beads and the SR beads, and/or the blend of the TPR beads group of one or more, at the appropriate quantity which achieves the target medicine movement study kind of profile which is ideal with the patient who needs this kind of medication vis-a-vis the dosage plan of 1 day 1 time it fills up in the gelatin capsule, or the method of including the process which is compressed in the usual tablet or the collapse lock inside the buccal cavity. 22. The aforementioned organic acid lamination conversion and SR coating, each of medicine lamination conversion, and outer part delay time coating, pharmacy is applied from the solution or the water dispersant in approved possible solvent system, in claim 21 method of statement. 23. Process below: g) With option, with solvent coacervation or either of porous membrane coating the process which the medicine content beads the sense of taste mask is done, h) Granulating sugar alcohol or the saccharide or these combinations, and collapse medicine which possess the mean diameter of each approximately 30 .micro.m or less, the process which forms the divination detachable fine granule which possesses the mean diameter of approximately 400 .micro.m or less, i) The multiplex coating beads and the divination detachable fine granule the process which is mixed at ratio with the multiplex coating beads and the fine granule of approximately 1:6- approximately 1:2, and j) The blend process (i), the process which with usual revolution tablet press is compressed in the collapse lock inside the buccal cavity furthermore is included, in claim 21 method of statement. 24. Pressing operation to the collapse lock inside the aforementioned buccal cavity, making use of the usual revolution tablet press which has the external lubricating system, the die/di and punch includes the process which the lubrication is done before the compressing, in claim 23 method of statement. 25. The aforementioned medicine shape, in regard to remedy the IR beads group and the SR beads group of the weak basic nitrogen (N) content selective [serotonin] 5-HT3 cutoff medicine of the effective quantity, and/or includes the TPR beads group of one or more, the discharge feature where each of the multiplex coating beads group differs after the specified delay time is shown, in claim 21 method of statement.
法律状态
(JP2016014048) LEGAL DETAILS FOR JP2016014048  Actual or expected expiration date=2027-01-29    Legal state=ALIVE    Status=PENDING     Event publication date=2015-09-25  Event code=JP/APP  Event indicator=Pos  Event type=Examination events  Application details  Application country=JP JP2015188001  Application date=2015-09-25  Standardized application number=2015JP-0188001     Event publication date=2015-10-26  Event code=JP/A621  Event indicator=Pos  Event type=Examination events  Written request for application examination  Effective date of the event=2015-10-26  JAPANESE INTERMEDIATE CODE: A621     Event publication date=2016-01-28  Event code=JP/A  Event indicator=Pos  Event type=Examination events  Published application  Publication country=JP  Publication number=JP2016014048  Publication stage Code=A  Publication date=2016-01-28  Standardized publication number=JP2016014048     Event publication date=2016-10-13  Event code=JP/A131  Event indicator=Neg  Event type=Examination events  Notification of reasons for refusal  Effective date of the event=2016-10-13  JAPANESE INTERMEDIATE CODE: A131     Event publication date=2017-01-12  Event code=JP/A601  Event type=Examination events  Written request for extension of term  Effective date of the event=2017-01-12  JAPANESE INTERMEDIATE CODE: A601
专利类型码
A
国别省市代码
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