WO2012141502A2 - Comprimé de type à libération prolongée contenant de l'aceclofénac - Google Patents

Comprimé de type à libération prolongée contenant de l'aceclofénac Download PDF

Info

Publication number
WO2012141502A2
WO2012141502A2 PCT/KR2012/002769 KR2012002769W WO2012141502A2 WO 2012141502 A2 WO2012141502 A2 WO 2012141502A2 KR 2012002769 W KR2012002769 W KR 2012002769W WO 2012141502 A2 WO2012141502 A2 WO 2012141502A2
Authority
WO
WIPO (PCT)
Prior art keywords
weight
aceclofenac
tablet
release layer
controlled release
Prior art date
Application number
PCT/KR2012/002769
Other languages
English (en)
Korean (ko)
Other versions
WO2012141502A3 (fr
Inventor
어진
한창균
정현근
김양중
김종걸
이정화
하남성
Original Assignee
안국약품 주식회사
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 안국약품 주식회사 filed Critical 안국약품 주식회사
Priority to MX2013011891A priority Critical patent/MX346466B/es
Priority to BR112013026473-0A priority patent/BR112013026473B1/pt
Publication of WO2012141502A2 publication Critical patent/WO2012141502A2/fr
Publication of WO2012141502A3 publication Critical patent/WO2012141502A3/fr

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/216—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • A61K9/2086—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat
    • A61K9/209—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat containing drug in at least two layers or in the core and in at least one outer layer
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • A61K9/2086—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat

Definitions

  • the present invention relates to an aceclofenac-containing controlled release tablet, which will be described in more detail, wherein the slow-release layer is composed of a multi-layer structure having a rapid-release layer and a slow-release layer.
  • the present invention relates to aceclofenac-containing controlled release tablets containing polyethylene oxide, which are designed to be taken once daily while having a much smaller size than the conventional controlled release substrate.
  • Aceclofenac is a nonsteroidal anti-inflammatory analgesic. It has better absorption in inflammatory tissues than other non-steroidal anti-inflammatory drugs, and has an excellent inhibitory effect on the production of the bioactive substance, prostagladin, which causes arthritis, spondylitis, toothache, and post-traumatic inflammation. It is known to be effective in low back pain, sciatica and postoperative pain.
  • COX-2 is selectively blocked to reduce the production of prostaglandin, thereby reducing the side effects including gastrointestinal disorders and having high stability.
  • aceclofenac preparations having such a pharmacological action tablets to be taken 100 mg twice a day and capsules to be taken twice a day to improve bioavailability are commercially available.
  • aceclofenac oral solution is inconvenient to be taken twice daily at 12 hour intervals.
  • sustained release preparations that can reduce the frequency of aceclofenac preparations.
  • the sustained-release preparation is much larger than the rapid-release preparation, it has been a very important technical task to reduce the size of the sustained-release tablet as much as possible to improve the convenience of the patient.
  • slow release tablets are also important to control the rate of release, but the technique of making the tablet size appropriate is more difficult and requires more research.
  • Korean Patent Laid-Open Publication No. 2006-0117572 (published date; November 17, 2006) includes a controlled-release aceclofenac preparation that sustains drug efficacy for 24 hours with a once-daily administration. I introduce it.
  • the formulation is 57 to 58.29% by weight of aceclofenac powder coated with ethyl cellulose; 14.28% by weight calcium monohydrogen phosphate; Lactose 24-25%; 2.86 wt% magnesium stearate; And 0.57% by weight of hard silicic anhydride.
  • Korean Patent Publication No. 2010-0064015 (published date: June 14, 2010) is a rapid release layer containing aceclofenac, water-soluble additives, pH regulators, disintegrants, fillers and lubricants, and aceclofenac, a release control polymer , A controlled release formulation comprising a sustained release layer comprising a fat soluble surfactant, a filler and a lubricant, wherein the pH adjusting agent is sodium hydrogen carbonate.
  • the formulation is a two-layered tablet having a fast-release layer and a sustained-release layer, which has the advantage of being manufactured by a general purification process without using a fluidized bed coater, but especially since the size of one tablet exceeds 480 mg and its size is very large. Dosing patients or older people may cause significant inconvenience in taking it.
  • the problem to be solved by the present invention is to prepare aceclofenac controlled release tablets that can be taken once a day in a simple and inexpensive manufacturing process compared to the prior art, in particular by reducing the size of one tablet significantly to 300 ⁇ 350mg long-term patients It is to provide aceclofenac-containing controlled release tablets that provide an optimal drug dissolution profile to improve the ease of taking for the elderly and to maintain an effective blood concentration during the administration.
  • the present invention comprises aceclofenac as an active ingredient, in the controlled release tablet of a multi-layer structure having a fast-release layer and a slow-release layer adjacent to each other,
  • the rapid release layer is 25 to 35% by weight of aceclofenac based on the weight of the tablet; 3 to 6 wt% of a disintegrant selected from croscarmellose sodium, crospovidone, and sodium starch glycolate; 10 to 14% by weight of an excipient selected from dimannitol, lactose and microcrystalline cellulose; 0.5 to 1.5% by weight of a binder selected from hydroxypropyl cellulose, povidone, methyl cellulose and gelatin; It consists of 1-2% by weight of lubricant selected from light silicic anhydride, talc, magnesium stearate,
  • the sustained release layer is 28 to 38% by weight of acecrofenac based on the weight of the tablet; 6-10% by weight of hypromellose; 0.7-9 wt% polyethylene oxide; 4-7 wt% of poorly soluble excipients selected from microcrystalline cellulose, corn starch, potato starch and wheat starch; 0.5 to 1.5% by weight of a binder selected from hydroxypropyl cellulose, povidone, methyl cellulose and gelatin; It consists of 1 to 2% by weight of a lubricant selected from light silicic anhydride, talc, magnesium stearate,
  • the weight of one tablet is 300 ⁇ 350mg, the content of aceclofenac contained herein is characterized in that 200mg.
  • Aceclofenac-containing controlled release tablets of the present invention can express sufficient anti-inflammatory analgesic effect by taking only once a day, and particularly, the weight of one tablet is 300-350 mg, which is much smaller in size than conventional sustained-release tablets, and thus the convenience of taking There is an improved effect.
  • the controlled release tablet of the present invention is a tablet composed of a two-layer structure of a rapid release layer and a sustained release layer, and can be quickly manufactured at a low cost by using a general high speed mixer and a tableting machine, and realize immediate and continuous drug release after taking It has the effect of maximizing the therapeutic effect.
  • FIG. 4 is a graph showing the dissolution test results for Example 2, Comparative Examples 1 and 2.
  • FIG. 4 is a graph showing the dissolution test results for Example 2, Comparative Examples 1 and 2.
  • Aceclofenac-containing controlled release tablet is composed of a multi-layered structure having a rapid release layer and a sustained release layer adjacent to each other, the rapid release layer is composed of aceclofenac and disintegrants, excipients, binders and lubricants as active ingredients,
  • the emissive layer consists of aceclofenac and a sustained release base, excipients, binders and glidants.
  • the rapid release layer and the sustained release layer may be formed in a two-layer structure stacked up and down, or may be composed of a three-layer structure in which the rapid release layer is stacked up and down with the sustained release layer as an intermediate layer.
  • the controlled release tablet is the weight of one tablet of 300 ⁇ 350mg, the content of the active ingredient aceclofenac is characterized in that the daily effective amount of 200mg.
  • the aceclofenac is preferably included so as to be divided by 25 to 35% by weight in the immediate release layer and 28 to 38% by weight in the slow release layer based on the total weight of the tablet.
  • the rapid release layer contains aceclofenac 80 ⁇ 110mg
  • the slow release layer contains 90 ⁇ 120mg of aceclofenac.
  • any one or more selected from croscarmellose sodium, crospovidone, and sodium starch glycolate may be used, and the content thereof is 3 to 6 wt% based on the weight of the tablet.
  • any one or more selected from dimannitol, lactose, microcrystalline cellulose the content is 10 to 14% by weight.
  • any one or more selected from hydroxypropyl cellulose, povidone, methyl cellulose and gelatin may be used, and the content thereof is 0.5 to 1.5% by weight.
  • the lubricant may be any one or more selected from light silicic anhydride, talc, magnesium stearate, and glyceryl behenate, and the content thereof is 1 to 2 wt%.
  • croscarmellose sodium is used as a disintegrant, microcrystalline cellulose and di-mannitol as excipients, hydroxypropyl cellulose and povidone as binders, magnesium stearate and hard silicic acid as lubricants.
  • the sustained release layer comprises a sustained release base, which is a feature of the present invention, wherein the sustained release substrate includes 6-10 wt% of hypromellose, which is a hydrophilic polymer material, and 0.7-9 wt% of polyethylene oxide.
  • the hypromellose uses a viscosity of 4000 cps
  • the polyethylene oxide has a molecular weight of 900,000 to 5,000,000.
  • the dissolution rate of the active ingredient is too fast to achieve the desired slow release effect, on the contrary the content of the hypromellose If the content is 10% by weight or more, or the content of polyethylene oxide is 9% by weight or more, the dissolution rate of the active ingredient is too slow to obtain an effective release effect after taking.
  • the viscosity of the hypromellose is more than 4000cps
  • the release rate of the main component is too slow, if less than 4000cps release rate is too fast to obtain a normal release effect.
  • the molecular weight of the polyethylene oxide is less than 900,000, the release of the main component occurs too fast, if exceeding 5,000,000 the release of the main component is too slow to obtain the desired sustained release effect.
  • Another feature of the present invention is an excipient of the sustained release layer, 4 to 7% by weight of any one or more poorly soluble excipient selected from microcrystalline cellulose, corn starch, potato starch, wheat starch. If a water-soluble excipient such as lactose or dimannitol is used in the sustained release layer, elution proceeds much faster than when the same amount of the poorly soluble excipient is used. Therefore, when water-soluble excipients are used, in order for the present invention to achieve the desired sustained release effect, a larger amount of excipient must be added, or a larger amount of sustained release agent, which is the weight of the tablet itself, which is the object of the present invention. Cause to increase. Therefore, the use of poorly soluble excipients as excipients of the sustained release layer is one of the very important factors that can reduce the size and weight of the controlled release tablet according to the present invention.
  • the binder of the sustained release layer may be any one or more selected from hydroxypropyl cellulose, povidone, methyl cellulose, gelatin, the content is 0.5 to 1.5% by weight.
  • the lubricant may be used any one or more selected from hard silicic anhydride, talc, magnesium stearate, the content is 1 to 2% by weight.
  • microcrystalline cellulose is used as an excipient, hydroxypropyl cellulose as a binder, and magnesium stearate as a lubricant.
  • Aceclofenac-containing controlled release tablets according to the present invention can be prepared according to the conventional tableting method for oral administration tablets, but are preferably prepared by a wet method. That is, the rapid release layer composition and the sustained release layer composition are prepared by granulating, drying, and sizing the components included in the rapid release layer and the sustained release layer, respectively, and using the conventional tableting machine, the compositions are two-layer structure or three layers. Tableting into a tablet form of the structure completes the controlled release tablet of the present invention.
  • the rapid release layer composition and the sustained release layer composition were prepared by the compositions shown in Tables 1 and 3, respectively, and the tablets were compressed into tablets in which the rapid release layer and the sustained release layer were laminated in a two-layered structure. After that, a conventional film coating base was coated thereon to prepare aceclofenac controlled release tablets according to the present invention.
  • 1 of the rapid release layer 2 is an active ingredient, 2 is a disintegrant, 3 is an excipient, 4 is a binder, 5 is a lubricant, 1 is an active ingredient, 2 is a sustained release substrate, 3 is Poorly soluble excipient, 4 represents a binder, 5 represents a lubricant.
  • Example 1 Example 2
  • Example 3 Content (mg) weight% Content (mg) weight% Content (mg) weight% Immediate release layer 1
  • Slow-release layer 1 Aceclofenac 100.0 31.94 100 31.44 100.0 30.95 2 Hypromellose 20.0 6.39 25.0 7.86 30.0 9.26 2 Polyethylene oxide 6.4 2.0
  • Example 5 Content (mg) weight% Content (mg) weight% Immediate release layer 1 Aceclofenac 100.0 31.84 100.0 29.23 2 croscarmellose sodium 15.0 4.78 15.0 4.38 3 di-mannitol 20.0 6.37 20.0 5.85 3 Microcrystalline cellulose 20.0 6.37 20.0 5.85 4 povidone K30 2.0 0.64 2.0 0.58 4 hydroxypropyl cellulose 1.0 0.32 1.0 0.29 5 light anhydrous silicic acid 3.0 0.96 3.0 0.88 5 magnesium stearate 2.0 0.64 2.0 0.58 sub Total 163.0 51.89 163.0 47.65 Slow-release layer 1 Aceclofenac 100 31.84 100 29.23 2 Hypromellose 25.0 7.96 25.0 7.31 2 Polyethylene oxide 2.4 0.76 30.4 8.89 3 Microcrystalline cellulose 16.7 5.32 16.7 4.88 4 hydroxypropyl cellulose 3.0 0.96 3.0 0.88 5 magnesium stearate 4.0 1.27 4.0 1.17 sub Total 151.1 48.11 179.
  • Example 7 Content (mg) weight% Content (mg) weight% Immediate release layer 1 Aceclofenac 80.0 25.27 110.0 34.49 2 croscarmellose sodium 12.0 3.79 16.5 5.17 3 di-mannitol 16.0 5.05 22.0 6.90 3 Microcrystalline cellulose 16.0 5.05 22.0 6.90 4 povidone K30 1.6 0.51 2.2 0.69 4 hydroxypropyl cellulose 0.8 0.25 1.1 0.34 5 light anhydrous silicic acid 2.4 0.76 3.3 1.03 5 magnesium stearate 1.6 0.51 2.2 0.69 sub Total 130.4 41.20 179.3 56.23 Slow-release layer 1 Aceclofenac 120.0 37.91 90.0 28.22 2 Hypromellose 30.0 9.48 22.5 7.06 2 Polyethylene oxide 7.7 2.43 5.8 1.81 3 Microcrystalline cellulose 20.0 6.33 15.0 4.71 4 hydroxypropyl cellulose 3.6 1.14 2.7 0.85 5 magnesium stearate 4.8 1.52 3.6 1.13 sub Total 186.1
  • the immediate release layer composition and the sustained release layer composition were prepared by the composition as shown in Table 4, and the tablets were compressed into tablets in which the rapid release layer and the sustained release layer were laminated in a two-layered structure.
  • a conventional film coating base was coated thereon to prepare aceclofenac controlled release tablets according to the present invention.
  • lactose and dimannitol which are water-soluble excipients, were used instead of poorly soluble excipients as excipients in the sustained release layer.
  • the dissolution test was performed for each of the aceclofenac controlled release tablets prepared according to the above Examples and Comparative Examples, and the results are shown in FIGS. 1 to 4.
  • the comparative dissolution test conditions were carried out under the condition of rotating the paddle (paddle) at 50rpm in pH 6.8 eluent by the comparative dissolution test method of the drug equivalence standard.
  • the aceclofenac controlled release tablet of the present invention is almost uniform for each time period for 24 hours by the immediate and continuous release of the drug in the immediate release layer and the sustained release layer It was confirmed that the release rate.
  • Figures 1 and 2 confirm that the dissolution rate is also proportionally changed by the content of the sustained release substrate hypromellose and polyethylene oxide contained in the sustained release layer. Therefore, by controlling the content of the sustained release substrate, it is possible to prepare a sustained release tablet having various release patterns.
  • FIG. 4 shows that when a water-soluble excipient such as lactose or dimannitol is used as an excipient used in the sustained release layer, the drug is rapidly released to obtain a normal sustained release effect. Therefore, in order to increase the normal sustained release effect, an additional excipient or a sustained release agent must be added to the sustained release layer, which causes an increase in the weight of the tablet itself.
  • a water-soluble excipient such as lactose or dimannitol

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Emergency Medicine (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

La présente invention concerne un comprimé de type à libération prolongée contenant de l'aceclofénac. En particulier, le comprimé a une structure multi-couches comprenant une couche à libération rapide et une couche à libération lente adjacentes l'une à l'autre. La couche à libération lente comprend un polymère hydrophile, de l'hypromellose et du poly(oxyde d'éthylène) comme matières à libération lente. Bien que le comprimé selon la présente invention ait une dimension encore plus petite que celle d'un comprimé classique de type à libération prolongée, il est conçu pour un dosage d'une fois par jour possible.
PCT/KR2012/002769 2011-04-13 2012-04-12 Comprimé de type à libération prolongée contenant de l'aceclofénac WO2012141502A2 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
MX2013011891A MX346466B (es) 2011-04-13 2012-04-12 Comprimido de tipo liberacion controlada que contiene aceclofenaco.
BR112013026473-0A BR112013026473B1 (pt) 2011-04-13 2012-04-12 Comprimido do tipo liberação controlada contendo aceclofenaco

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR10-2011-0034022 2011-04-13
KR1020110034022A KR101310099B1 (ko) 2011-04-13 2011-04-13 아세클로페낙 함유 방출제어형 정제

Publications (2)

Publication Number Publication Date
WO2012141502A2 true WO2012141502A2 (fr) 2012-10-18
WO2012141502A3 WO2012141502A3 (fr) 2013-01-03

Family

ID=47009839

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2012/002769 WO2012141502A2 (fr) 2011-04-13 2012-04-12 Comprimé de type à libération prolongée contenant de l'aceclofénac

Country Status (4)

Country Link
KR (1) KR101310099B1 (fr)
BR (1) BR112013026473B1 (fr)
MX (1) MX346466B (fr)
WO (1) WO2012141502A2 (fr)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR102236650B1 (ko) * 2019-04-16 2021-04-07 한국유나이티드제약 주식회사 아세클로페낙을 포함하는 약학조성물 및 이의 제조방법
KR102426727B1 (ko) 2020-04-17 2022-07-28 성균관대학교산학협력단 방출 속도 조절 경구용 약물 전달 장치 및 방출 속도 조절 경구용 약물 전달 장치의 제조 방법

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6599529B1 (en) * 1997-09-11 2003-07-29 Nycomed Danmark A/S Modified release multiple-units compositions of non-steroid anti-inflammatory drug substances (NSAIDs)
KR20040077244A (ko) * 2003-02-28 2004-09-04 한국유나이티드제약 주식회사 제어방출형 경구 펠렛제제 및 그 제조방법
JP2005232185A (ja) * 2003-03-06 2005-09-02 Astellas Pharma Inc 放出制御用医薬組成物およびその製造方法
US20070092573A1 (en) * 2005-10-24 2007-04-26 Laxminarayan Joshi Stabilized extended release pharmaceutical compositions comprising a beta-adrenoreceptor antagonist
KR20090022612A (ko) * 2007-08-31 2009-03-04 주식회사 드림파마 신규한 서방출형 아세클로페낙 제제 조성물 및 그의제조방법
KR20100064015A (ko) * 2008-12-04 2010-06-14 한국유나이티드제약 주식회사 제어 방출성 아세클로페낙을 함유하는 경구 제제의 조성물 및 그의 제조방법

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6599529B1 (en) * 1997-09-11 2003-07-29 Nycomed Danmark A/S Modified release multiple-units compositions of non-steroid anti-inflammatory drug substances (NSAIDs)
KR20040077244A (ko) * 2003-02-28 2004-09-04 한국유나이티드제약 주식회사 제어방출형 경구 펠렛제제 및 그 제조방법
JP2005232185A (ja) * 2003-03-06 2005-09-02 Astellas Pharma Inc 放出制御用医薬組成物およびその製造方法
US20070092573A1 (en) * 2005-10-24 2007-04-26 Laxminarayan Joshi Stabilized extended release pharmaceutical compositions comprising a beta-adrenoreceptor antagonist
KR20090022612A (ko) * 2007-08-31 2009-03-04 주식회사 드림파마 신규한 서방출형 아세클로페낙 제제 조성물 및 그의제조방법
KR20100064015A (ko) * 2008-12-04 2010-06-14 한국유나이티드제약 주식회사 제어 방출성 아세클로페낙을 함유하는 경구 제제의 조성물 및 그의 제조방법

Also Published As

Publication number Publication date
MX2013011891A (es) 2014-03-31
BR112013026473B1 (pt) 2021-10-13
BR112013026473A8 (pt) 2018-01-30
MX346466B (es) 2017-03-22
WO2012141502A3 (fr) 2013-01-03
KR20120116545A (ko) 2012-10-23
KR101310099B1 (ko) 2013-09-23
BR112013026473A2 (pt) 2016-12-20

Similar Documents

Publication Publication Date Title
KR101612931B1 (ko) 1일 1회 투여로 약리학적 임상 효과를 제공하는 모사프리드 서방성 제제
KR20070027560A (ko) 코팅된 정제 제형 및 방법
KR20140085411A (ko) 올메사탄 메독소밀 및 로수바스타틴 또는 그의 염을 포함하는 약학 조성물
KR20070021565A (ko) 메트포르민 서방정 및 그의 제조방법
WO2020138791A2 (fr) Préparation à libération prolongée comprenant du tofacitinib ou un sel pharmaceutiquement acceptable associé et son procédé de fabrication
AU2009265099A1 (en) Sustained release pharmaceutical compositions comprising Quetiapine
KR20120033557A (ko) 레보드로프로피진을 포함하는 속효성과 지속성을 동시에 갖는 약제학적 조성물
CZ298851B6 (cs) Tableta pro rízené podávání úcinných látek
WO2012008675A1 (fr) Comprimé à libération prolongée contenant de la trimébutine
WO2012141502A2 (fr) Comprimé de type à libération prolongée contenant de l'aceclofénac
WO2018143511A1 (fr) Comprimé oral triple à libération prolongée contenant de la prégabaline
WO2004096182A1 (fr) Comprimes matriciels a liberation prolongee de carvedilol
WO2010024576A2 (fr) Cachet à libération prolongée contenant du talniflumate avec absorption par l'organisme améliorée
CA2717900C (fr) Formulation galenique orale contenant du ketorolac et des vitamines du complexe b, dans laquelle la vitamine b6 se trouve dans une couche externe separee des autres principes actifs
KR20210073285A (ko) 프로톤펌프억제제 및 모사프리드를 포함하는 유핵정 제제
WO2015108392A1 (fr) Petit comprimé pharmaceutique contenant de l'ésoméprazole
US20150359795A1 (en) High drug load pharmaceutical compositions with controllable release rate and production methods thereof
KR100795419B1 (ko) 암로디핀 및 아스피린을 함유하는 약학 제제
KR102389339B1 (ko) 방출 제어되는 고함량 탐스로신 정제 조성물 및 이의 제조방법
KR101265491B1 (ko) 사포그릴레이트염산염을 함유하는 용출률이 조절된 경구용 다층정제 및 이의 제조방법
US8512746B2 (en) Extended release pharmaceutical compositions of levetiracetam
WO2012111961A2 (fr) Comprimé à libération prolongée, administré par voie orale, contenant de la tianeptine ou un sel pharmaceutiquement acceptable de celle-ci
KR20210012082A (ko) 미라베그론 및 탐스로신을 포함하는 약학 조성물
KR20190142809A (ko) 실로스타졸과 스타틴계약물을 함유하는 약학 조성물
CA2481377A1 (fr) Compositions pharmaceutiques antihistaminiques et decongestionnantes

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 12770908

Country of ref document: EP

Kind code of ref document: A2

WWE Wipo information: entry into national phase

Ref document number: MX/A/2013/011891

Country of ref document: MX

NENP Non-entry into the national phase

Ref country code: DE

WWE Wipo information: entry into national phase

Ref document number: 2013/12118

Country of ref document: TR

122 Ep: pct application non-entry in european phase

Ref document number: 12770908

Country of ref document: EP

Kind code of ref document: A2

REG Reference to national code

Ref country code: BR

Ref legal event code: B01A

Ref document number: 112013026473

Country of ref document: BR

ENP Entry into the national phase

Ref document number: 112013026473

Country of ref document: BR

Kind code of ref document: A2

Effective date: 20131014