WO2010024576A2 - Cachet à libération prolongée contenant du talniflumate avec absorption par l'organisme améliorée - Google Patents

Cachet à libération prolongée contenant du talniflumate avec absorption par l'organisme améliorée Download PDF

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Publication number
WO2010024576A2
WO2010024576A2 PCT/KR2009/004734 KR2009004734W WO2010024576A2 WO 2010024576 A2 WO2010024576 A2 WO 2010024576A2 KR 2009004734 W KR2009004734 W KR 2009004734W WO 2010024576 A2 WO2010024576 A2 WO 2010024576A2
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WO
WIPO (PCT)
Prior art keywords
sustained
tablet
release tablet
cellulose
release
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Application number
PCT/KR2009/004734
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English (en)
Korean (ko)
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WO2010024576A3 (fr
Inventor
이정은
신병철
조선행
성하수
안신병
권무길
김종택
Original Assignee
한국화학연구원
근화제약 주식회사
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Publication of WO2010024576A2 publication Critical patent/WO2010024576A2/fr
Publication of WO2010024576A3 publication Critical patent/WO2010024576A3/fr

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    • 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 a talni flumate-containing sustained-release tablet with enhanced absorption in the body, and more specifically, using a nucleating tablet, a double-crystal tablet or a hydrophilic polymer containing a hydrophilic polymer so as to stably sustained release using an adjuvant that can enhance absorption in the body and
  • the present invention relates to a sustained-release tablet for talniflumate in the form of a drug-coated tablet having a drug coating layer.
  • Talniflumate is used for pain relief after surgery or extraction and for the treatment of inflammation and pain in inflammatory diseases such as rheumatoid arthritis and osteoarthritis.
  • the dose is 370 mg three times daily for adults, and 740 mg three times daily for severe disease.
  • the method of administration is typically a poorly soluble drug which is taken orally and is almost insoluble in water. In order to improve this and increase the bioavailability, a lot of research is being conducted. Representative examples include the use of cosolvents, the addition of counterions to poorly soluble materials to form salts of acids or bases, and the combination of polymer compounds or ligands to form soluble complexes.
  • Republic of Korea Patent Publication No. 10-2001-0075695 and 10-2002-0062302 consists of applying a water-insoluble coating film to the spherical sugar granules, coding the tolterodine drug layer thereon, and then avoiding the release control film made of water-insoluble polymer.
  • a method for producing tolterodine sustained release beads is introduced.
  • Korean Patent Laid-Open Publication No. 10-2001-009439 discloses a technique for tableting a sephae antibiotic with hydroxypropylmethylcellulose and vinylpyrrolidone vinyl acetate copolymer to sustain release. Recently, Shin-Etsu, Dow Chemical and others have introduced the preparation of sustained-release matrix tablets using cellulose polymers.
  • Korean Patent No. 0379299 discloses a method of preparing a solid dispersion using a mixer or a spray dryer after dissolving the felodipine and the enteric polymer in a mixed solvent of a polar solvent and a non-polar solvent
  • Republic of Korea Patent Publication No. 0060730 No. discloses that sustained-release preparations can be prepared by dissolving the sustained-release acrylic polymer in an organic solvent and then wetting and mixing it with a mixed powder of poorly soluble drugs and excipients to obtain granular material and containing polyethylene glycol as an wicking accelerator. Doing.
  • the drug release rate is appropriately controlled to facilitate patient comfort and reduce side effects while obtaining excellent therapeutic effects.
  • the present inventors have conducted research and efforts to supplement the shortcomings of the conventional talni flu mate single-core form of immediate release formulations, improve the solubility of the drug by using an adjuvant that can enhance the absorption in the body to improve the absorption in the west
  • the present invention has been accomplished by improving the rate of drug release by using nucleated tablets and multi-layered tablet methods of sex formulations and sustained release mechanisms using drug-coated tablets.
  • the present invention is characterized by a talni flu mate sustained-release tablet containing talni flu mate as an active ingredient, a dissolution aid for promoting absorption and a hydrophilic polymer for sustained release.
  • Tablets of talni flu mate according to the present invention can increase the dissolution of talni flu mate in the case of immediate release, so that the bioavailability is high, when the sustained-release tablet is made, the manufacturing process is relatively easy, the release rate can be controlled, The same effect can be obtained at a smaller dose than commercially available immediate release talniflumate 370 and 720 mg formulations, while the sustained release exhibits excellent dissolution properties that allow the drug to be released slowly at a constant rate in the body. There is an advantage that the discomfort to administer can be reduced to twice daily administration at low doses.
  • Figure 1 shows the tablet form of the nucleated tablet, multi-layered tablet and drug-coated tablet according to the present invention.
  • 3 is a graph showing the dissolution rate over time in the dissolution test according to the experimental example of the Examples 6 to 10 tablets.
  • Figure 4 is a graph showing the dissolution rate over time in the dissolution test according to the experimental example of the Examples 11 to 14 tablets.
  • talni flu mate sustained-release tablet containing a talni flu mate as an active ingredient, a dissolution aid for promoting absorption and a hydrophilic polymer for sustained release.
  • Talni flu mate is a representative poorly soluble drug, it is necessary to use a dissolution aid to promote absorption to increase the body absorption.
  • the dissolution aid that can enhance the dissolution and absorption in the body of the tablet is preferably mixed with anionic or nonionic surfactants, especially bile salts for the purpose of promoting absorption in the gastrointestinal tract.
  • the anionic surfactants include sodium lauryl sulfate, or bile salt derivatives such as taurodioxycholine acid, choline acid, deoxycholine acid, kenodeoxycholine acid, urosodeoxycholine acid, and dehydrocholine acid.
  • the nonionic surfactants include twins and spans including polyethylene oxide, specifically, twin 20, twin 40, twin 60, twin 80, span 20, span 40, span 60 and span 80.
  • Dissolution aid is characterized in that one or a mixture of two or more selected from the anionic or nonionic surfactant, it is preferably included in 1 to 50% by weight relative to the total weight of the tablet.
  • Hydrophilic polymers that can be used in the sustained-release tablet according to the present invention include talniflumate, cellulose, polyalkylene oxide, alginate, polyvinyl alcohol, polyvinylpyrrolidone, polyalkylglycol, polydextrin, pectin, povidone, carbo It is characterized in that one or two or more selected from mercury and eudragit, more specifically hydroxypropylmethylcellulose, polyethylene oxide, sodium alginate, polyvinyl alcohol, polyvinylpyrrolidone, polyethylene glycol, poly Dextrin, pectin, methyl cellulose, cellulose acetate, hydroxymethyl cellulose, ethyl cellulose, povidone, carbomer, and one or more mixtures of Eudragit, characterized in that 1 to 50% by weight of the total tablet It is preferably included in%.
  • the talni flu mate sustained-release tablet is composed of a sustained portion and a rapid release portion, wherein the sustained portion forms a core layer, and the outer layer surrounding the core layer is a nucleus tablet or a double crystal in which the sustained portion and the immediate release portion each layer. Can be refined.
  • the immediate release base includes lactose, white sugar, glucose, sucrose, sugars such as mannitol or sorbitol, starch such as potato, wheat and corn, minerals such as calcium carbonate, calcium sulfate, sodium bicarbonate or sodium chloride, and licorice. It is preferable to use a compound selected from plant powders such as powders and solvent powders.
  • the sustained-release tablet of the present invention can control the release characteristics of the active ingredient according to the selection and content of the hydrophilic polymer, the binder, and the disintegrant contained in the sustained-release tablet. For example, increasing the viscosity of a hydrophilic polymer decreases the release rate of the drug.
  • sustained-release tablet of the present invention As a preferable embodiment of the sustained-release tablet of the present invention,
  • the rapid-release tablet is added to the granules, followed by mixing and tableting into nucleated tablets or double tablets.
  • the sustained-release tablet of 1) may be coated with a coating solution containing talni flu mate to prepare a sustained-release tablet having a coating layer.
  • the talni flu mate sustained-release tablet according to the present invention may further include one or more adjuvants of excipients, binders, lubricants, and colorants.
  • the excipient is one or two or more selected from lactose, microcrystalline cellulose, low substituted hydroxypropyl cellulose, corn starch, potato starch, wheat starch, white sugar, di-mannitol, precipitated calcium carbonate, dextrin, and pre-gelatinized starch. It is a mixture, preferably 10 to 30% by weight based on the total weight of the tablet.
  • the binder is one or a mixture of two or more selected from polyvinylpyrrolidone, hydroxypropyl cellulose, dextrin, gelatin, methyl cellulose, hydroxyethyl cellulose, hydroxymethyl cellulose, polyvinyl alcohol, paste, gum arabic, It is preferably included in an amount of 2 to 20% by weight based on the total weight of the tablet.
  • the disintegrant is one or a mixture of two or more selected from sodium starch glycolate, crospovidone, sodium chromosmellose, low-substituted hydroxypropyl cellulose, starch, carboxymethyl cellulose, and 0.1 to about the total weight of the tablet composition. It is preferably included in 10% by weight.
  • the lubricant is one or a mixture of two or more selected from magnesium stearate, talc, mousse silicic acid, and preferably contained in an amount of 0.1 to 10% by weight based on the total weight of the tablet.
  • the talni flu mate drug requiring sustained release may be prepared as a coating liquid by suspending together with the film coating agent and coated on the surface of the sustained release tablet.
  • the talni flu mate of the coating layer has a first release effect
  • the talni flu mate of the core tablet included with the hydrophilic polymer has a second release effect.
  • the amount of the coating liquid is preferably kept to a minimum in order to limit the size of the formulation and to effectively manufacture, and may be included in 1 to 10% by weight, preferably 2 to 8% by weight based on the total weight of the sustained-release formulation. It may be coated by a pan coating method, a fluidized bed coating method, an extrusion coating method and the like.
  • the polymer used in the coating solution is one or a mixture of two or more selected from polyvinyl alcohol, polypropylene glycol, acrylic acid copolymer, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, methyl cellulose, ethyl cellulose, and cellulose acetate.
  • a colorant may be included in the tablet of the present invention, and titanium dioxide, iron oxide, magnesium carbonate, calcium sulfate, magnesium oxide, magnesium hydroxide, aluminum lake, for example blue No. 1 aluminum lake, red No. 40 aluminum One or a mixture of two or more selected from the lakes may be used.
  • the granules were prepared by mixing talni flumate and sodium alginate, carbomer, hydroxypropylmethylcellulose or eudragit according to the component ratios of Table 1, followed by the addition of excipients, binders, disintegrants and glidants.
  • the granules prepared were compressed to prepare sustained release tablets.
  • the granules prepared in the weight ratio of Examples 1 to 5 were mixed with the rapid-release tablet compositions mixed in the ratios of Table 2 and tableted into double tablets.
  • Example 1 The tablets prepared in Example 1 were coated with respective drug-containing coating layers as shown in Table 3 below to prepare drug coated tablets.
  • Each of the sustained-release tablets prepared in Examples 1 to 14 was subjected to a dissolution test according to the paddle method under the following conditions, and the dissolution rate of talniflumate, an active ingredient from these sustained-release preparations, was measured over time. It was.
  • test conditions used for the dissolution test are as follows.
  • pH 6.8 phosphate buffer solution prepared by adjusting pH6.8 with 0.05 M potassium dihydrogen phosphate, 0.05 M sodium dihydrogen phosphate solution, and phosphoric acid + 1% polysorbate 80
  • the dissolution rate of the active ingredient was analyzed from the sample solution obtained every hour in the dissolution test. Dissolution rate analysis was performed at an absorbance of 285 nm using an ultraviolet-visible spectrophotometer.
  • Test Results The results of testing the dissolution rate over time are shown in FIG. 2 (Examples 1 to 5), FIG. 3 (Examples 6 to 10), and FIG. 4 (Examples 11 to 14).
  • sustained-release tablets exhibit the property of continually releasing active ingredient for 12 to 24 hours, so that the sustained-release tablet of the present invention is suitable for twice daily administration desired. I could confirm that. It can be seen that even with the same sustained-release tablet, it is possible to prepare talniflumate sustained-release tablets whose dissolution rate can be controlled according to the process step.
  • the sustained-release tablet of the present invention can be easily adjusted according to the selection and the content of the type of hydrophilic polymer to be contained.

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

Abstract

La présente invention concerne un cachet à libération prolongée contenant du talniflumate. Plus spécifiquement, la présente invention concerne un cachet à libération prolongée de talniflumate formé sous forme de cachet revêtu de médicament comprenant un cachet à noyau et un cachet à double couche ou à couche revêtue de médicament. Une aide de solubilisation est utilisée pour augmenter la solubilité du talniflumate qui est un médicament non soluble dans le cachet. Ce cachet contient des polymères hydrophiles destinés à stabiliser la libération prolongée dans l'organisme du patient. Le cachet à libération prolongée contenant du talniflumate de l'invention présente un processus de fabrication facile et est à même de contrôler la vitesse de libération. Par ailleurs, ce cachet possède une excellente efficacité de libération pour libérer de manière graduelle des composants médicamenteux dans l'organisme à une vitesse constante, comparé à des préparations à 720g et à 370g de talniflumate à libération immédiate classiques disponibles sur le marché. Par conséquent, ce cachet présente l'avantage de pallier l'inconvénient d'une administration en trois prises quotidiennes, celui-ci étant administré en une ou deux prises quotidiennes.
PCT/KR2009/004734 2008-08-27 2009-08-25 Cachet à libération prolongée contenant du talniflumate avec absorption par l'organisme améliorée WO2010024576A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR1020080084155A KR101018894B1 (ko) 2008-08-27 2008-08-27 체내 흡수가 증진된 탈니플루메이트 함유 서방정
KR10-2008-0084155 2008-08-27

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WO2010024576A2 true WO2010024576A2 (fr) 2010-03-04
WO2010024576A3 WO2010024576A3 (fr) 2010-06-17

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114869886A (zh) * 2022-01-04 2022-08-09 南京中医药大学 他尼氟酯在帕金森病防治中的应用

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101277021B1 (ko) * 2010-12-28 2013-06-24 주식회사 드림파마 위체류 약물 전달시스템을 이용한 경구용 방출제어형 레바미피드-함유 이층정 제제 및 그 제조방법
US20140377346A1 (en) * 2012-05-11 2014-12-25 Hanall Biopharma Co., Ltd. Bosentan controlled release oral preparation
KR101698809B1 (ko) * 2015-09-21 2017-01-24 한국화학연구원 천연 난용성 약물이 봉입된 다층 나노 입자를 포함하는 약학적 제제 및 이의 제조 방법
WO2018105756A1 (fr) * 2016-12-05 2018-06-14 정한수 Produit cosmétique comprenant des nanoparticules multicouches contenant à l'état encapsulé un remède naturel insoluble à titre de conservateur, et procédé de production dudit produit cosmétique

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20030003500A (ko) * 2001-07-03 2003-01-10 이범진 아세클로페낙을 함유하는 경제적인 경구용 제제의 조성 및제법
US20030180357A1 (en) * 2002-02-07 2003-09-25 Martino Alice C. Pharmaceutical tablet
WO2004006863A2 (fr) * 2002-07-17 2004-01-22 Rutgers, The State University Dispositifs therapeutiques pour croissance cellulaire structuree
US20060018934A1 (en) * 2002-08-05 2006-01-26 Navin Vaya Novel drug delivery system

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20030003500A (ko) * 2001-07-03 2003-01-10 이범진 아세클로페낙을 함유하는 경제적인 경구용 제제의 조성 및제법
US20030180357A1 (en) * 2002-02-07 2003-09-25 Martino Alice C. Pharmaceutical tablet
WO2004006863A2 (fr) * 2002-07-17 2004-01-22 Rutgers, The State University Dispositifs therapeutiques pour croissance cellulaire structuree
US20060018934A1 (en) * 2002-08-05 2006-01-26 Navin Vaya Novel drug delivery system

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114869886A (zh) * 2022-01-04 2022-08-09 南京中医药大学 他尼氟酯在帕金森病防治中的应用
CN114869886B (zh) * 2022-01-04 2023-01-03 南京中医药大学 他尼氟酯在帕金森病防治中的应用

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Publication number Publication date
WO2010024576A3 (fr) 2010-06-17
KR20100025427A (ko) 2010-03-09
KR101018894B1 (ko) 2011-03-04

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