KR100671714B1 - Micronized felodipine-containing sustained release formulation - Google Patents
Micronized felodipine-containing sustained release formulation Download PDFInfo
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- KR100671714B1 KR100671714B1 KR1020040091203A KR20040091203A KR100671714B1 KR 100671714 B1 KR100671714 B1 KR 100671714B1 KR 1020040091203 A KR1020040091203 A KR 1020040091203A KR 20040091203 A KR20040091203 A KR 20040091203A KR 100671714 B1 KR100671714 B1 KR 100671714B1
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
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- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4422—1,4-Dihydropyridines, e.g. nifedipine, nicardipine
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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
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2009—Inorganic compounds
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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
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
Abstract
본 발명은 미분화(微粉化)된 펠로디핀 함유 지속 방출성 제제에 관한 것으로서, 더욱 상세하게는 물에 난용성인 펠로디핀을 20㎛ 이내의 입자크기를 갖는 미세 분말로 분쇄하여 용출율을 개선하고, 여기에 직타용 서방기제로서 카르복시비닐 폴리머를 혼합하여 제제화함으로써 약물이 일정시간 동안 서서히 방출되도록 한 펠로디핀 함유 지속 방출성 제제에 관한 것이다.The present invention relates to a micronized pelodipine-containing sustained-release preparation, and more particularly, to pulverizing felodipine, which is poorly soluble in water, into a fine powder having a particle size of 20 μm, thereby improving dissolution rate. The present invention relates to a felodipine-containing sustained release formulation which is formulated by mixing carboxyvinyl polymer as a sustained release agent for direct application.
펠로디핀, 미분화, 지속 방출성, 직타용 서방기제, 카르복시비닐 폴리머Pelodipine, Micronized, Sustained Release, Sustained Release Agent, Carboxyvinyl Polymer
Description
도 1은, 실험예 1의 주성분에 따른 시간별 약물 방출율 시험 결과를 나타낸 그래프이다. 1 is a graph showing the results of the drug release rate test by time according to the main component of Experimental Example 1.
도 2는, 실험예 2의 서방기제량에 따른 시간별 약물 방출율 시험 결과를 나타낸 그래프이다. 2 is a graph showing the results of the drug release rate test for each hour according to the sustained-release amount of Experimental Example 2.
본 발명은 미분화(微粉化)된 펠로디핀 함유 지속 방출성 제제에 관한 것으로서, 더욱 상세하게는 물에 난용성인 펠로디핀을 20㎛ 이내의 입자크기를 갖는 미세 분말로 분쇄하여 용출율을 개선하고, 여기에 직타용 서방기제로서 카르복시비닐 폴리머를 혼합하여 제제화함으로써 약물이 일정시간 동안 서서히 방출되도록 한 펠로디핀 함유 지속 방출성 제제에 관한 것이다.The present invention relates to a micronized pelodipine-containing sustained-release preparation, and more particularly, to pulverizing felodipine, which is poorly soluble in water, into a fine powder having a particle size of 20 μm, thereby improving dissolution rate. The present invention relates to a felodipine-containing sustained release formulation which is formulated by mixing carboxyvinyl polymer as a sustained release agent for direct application.
일반적으로 의약품 복용시, 인체 내에서 신속하게 흡수되고 높은 약리활성을 나타내려면 약물이 제제로부터 신속하게 용출되어야 하는데, 약물의 용출속도는 체내에서의 흡수속도와 밀접한 관계를 가지고 있으며, 이는 혈액 중의 약물 농도를 결정하는 중요한 지표로서 약물의 용해도에 의한 영향이 매우 크다.In general, when taking a drug, the drug must be rapidly eluted from the preparation to be rapidly absorbed in the body and exhibit high pharmacological activity. The dissolution rate of the drug is closely related to the rate of absorption in the body. As an important indicator of the concentration, the solubility of the drug is very large.
펠로디핀(Ethylmethyl-4-(2, 3-dichlorophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate, C18H19Cl2NO4, M.W.: 384.26)은 칼슘 길항제로서 고혈압치료에 매우 효과적인 약물로 알려져 있으며, 물에는 녹지 않고 염화메틸렌과 에탄올에는 잘 녹는 특성을 가지고 있다.Pelodipine (Ethylmethyl-4- (2, 3-dichlorophenyl) -1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate, C 18 H 19 Cl 2 NO 4 , MW: 384.26) is a calcium antagonist It is known as a very effective drug for the treatment of hypertension. It is insoluble in water and soluble in methylene chloride and ethanol.
펠로디핀을 보다 효과적으로 투여하기 위한 많은 제형이 연구되어 왔는데, 대한민국 특허공고 제 1993-1803호에는 펠로디핀을 포함한 여러 가지 약물을 폴리비닐피롤리돈, 에틸셀룰로오스, 젤라틴, 히드록시프로필메틸셀룰로오스 등의 고분자를 이용하여 소미립자 및 캡슐화하여 용해도를 증가시키는 방법이 개시되어 있다. 그러나, 상기 특허의 방법은 가열 및 강산 등을 사용하여 제조하므로, 제조방법이 복잡하고 산 증기 등에 의한 질병을 유발할 수 있으므로 바람직한 방법이라고 볼 수 없다.Many formulations for more effective administration of felodipine have been studied. Korean Patent Publication No. 1993-1803 describes various drugs including felodipine such as polyvinylpyrrolidone, ethyl cellulose, gelatin, hydroxypropyl methyl cellulose, and the like. Disclosed is a method of increasing solubility by encapsulating small particles and encapsulation using a polymer. However, since the method of the patent is manufactured using heating and strong acid, etc., it is not a preferable method because the manufacturing method is complicated and can cause diseases caused by acid vapor.
또한, 대한민국 특허등록 제 137731호와 대한민국 특허등록 제 162106호에는 삼투압에 의한 방출 조절형 펠로디핀 정제가 개시되어 있는 바, 상기 특허들에 개시된 제조방법은 제조방법 자체가 복잡하고 약물의 방출을 위한 방출구를 별도로 구비해야 하는 등, 제제의 제조에 별도의 특수 장비가 요구되므로 역시 바람직한 방법이라고 볼 수 없다.In addition, Republic of Korea Patent Registration No. 137731 and Republic of Korea Patent Registration No. 162106 discloses controlled release pelodipine tablets by osmotic pressure, the manufacturing method disclosed in the patents are complicated manufacturing method itself and for the release of drugs It is also not a preferred method because separate special equipment is required for the preparation of the formulation, such as the provision of a separate outlet.
또한, 대한민국 특허공고 제 1995-2147호에는 난용성인 약물의 가용화를 위해 폴리에톡실화 지방산, 히드록실 지방산 및 지방 알콜, 크레모포아(cremophor), 폴리옥실 40 스테아레이트 등을 사용한 친수성 겔 시스템을 이용하였는데, 이들 가용화제는 위장관에 독성이 강한 첨가제로 알려져 있어 최근에는 이의 사용을 자제하고 있다. 또한 상기 특허에서는 가용화된 약물을 친수성 고분자인 히드록시프로필메틸셀룰로오스 등을 이용하여 친수성 겔 시스템을 만들고, 잔탄검이나 구아검 등의 검 종류를 이용하여 방출 조절을 보조하는 방법을 사용하고 있는데, 이러한 방법은 시험방법에 따라 재현성이 일정하지 않을 수 있으므로 개선이 요구되는 제조방법이라 할 수 있다. In addition, Korean Patent Publication No. 1995-2147 discloses a hydrophilic gel system using polyethoxylated fatty acid, hydroxyl fatty acid and fatty alcohol, cremophor, polyoxyl 40 stearate, and the like for solubilizing poorly soluble drugs. These solubilizers are known as additives that are highly toxic to the gastrointestinal tract and have recently been refrained from their use. In addition, the patent uses a method of assisting the release control by using a type of gum such as xanthan gum or guar gum to make a hydrophilic gel system using a hydrophilic polymer, such as hydroxypropylmethylcellulose. The method may be called a manufacturing method requiring improvement since reproducibility may not be constant according to a test method.
또한, 대한민국 특허등록 제 396443호에서는 난용성인 약물의 가용화를 위해 약물을 수용성 고분자인 폴리비닐피롤리돈과 함께 공통용매인 유기용매에 용해하고, 유동층 분무건조 코팅기를 사용하여 분무건조함으로써 가용화된 고체 분산체(Solid-Dispersants)를 제조하고, 여기에 서방기제를 혼합하여 지속 방출성 제제를 제조하는 방법이 개시되어 있으나, 이 또한 약물의 가용화 과정을 거쳐야 하고 습식 과립을 해야 하는 등의 복잡한 제조공정을 필요로 하는 단점이 있다.In addition, Korean Patent No. 396443 discloses a solubilized solid by dissolving a drug in a common solvent together with a polyvinylpyrrolidone as a water-soluble polymer and spray drying using a fluidized bed spray drying coater to solubilize a poorly soluble drug. There are disclosed methods for preparing solid-dispersants and mixing sustained-release agents to produce sustained release formulations, but this also involves complex preparation processes such as solubilization of the drug and wet granulation. There is a disadvantage that requires.
본 발명은 상기와 같은 문제점을 해결하기 위한 것으로, 본 발명의 목적은 물에 난용성인 펠로디핀을 20㎛ 이내의 입자크기를 갖는 미세 분말로 분쇄하여 용출율을 개선하고, 여기에 직타용 서방기제로서 카르복시비닐 폴리머를 혼합하여 제제화함으로써 약물이 일정시간 동안 서서히 방출되도록 한 펠로디핀 함유 지속 방출성 제제를 제공하는 것이다.The present invention is to solve the above problems, an object of the present invention is to grind the poorly soluble felodipine into fine powder having a particle size of less than 20㎛ to improve the dissolution rate, here as a sustained release agent for direct It is to provide a felodipine-containing sustained release formulation which is formulated by mixing the carboxyvinyl polymer to allow the drug to be released slowly over time.
본 발명의 펠로디핀 함유 지속 방출성 제제는 물에 난용성인 펠로디핀을 20㎛ 이내의 입자크기를 갖는 미세 분말로 분쇄하고, 여기에 직타용 서방기제로서 제제 전체중량 대비 2∼15중량%의 카르복시비닐 폴리머를 혼합하여 제조되는 것을 특징으로 한다. Pelodipine-containing sustained-release preparation of the present invention is pulverized poorly soluble felodipine into a fine powder having a particle size of less than 20㎛, and as a sustained-release agent for direct hitting, 2 to 15% by weight of carboxy It is characterized by being produced by mixing the vinyl polymer.
이하, 본 발명의 펠로디핀 함유 지속 방출성 제제의 제조방법을 상세히 설명한다.Hereinafter, the preparation method of the felodipine-containing sustained release preparation of the present invention will be described in detail.
1) 미분화(微粉化)된 펠로디핀의 제조1) Preparation of micronized felodipine
물에 난용성인 펠로디핀을 고속분쇄기를 이용하여 수회 분쇄함으로써 미분화된 펠로디핀을 제조한다. 이때 분쇄된 펠로디핀의 입자크기를 입자 분석기(Particle Analyzer)로 측정시, 20㎛ 이내의 입자가 99% 이상이 되도록 한다.Finely divided pelodipine is prepared by pulverizing felodipine, which is poorly soluble in water, several times using a high speed mill. At this time, when the particle size of the crushed pelodipine is measured by a particle analyzer (Particle Analyzer), the particles within 20 ㎛ to be 99% or more.
2) 펠로디핀 함유 지속 방출성 제제의 제조2) Preparation of Pelodipine-Containing Sustained-Release Formulations
상기에서 얻은 미분화된 펠로디핀에 서방기제로서 직타용 카르복시비닐 폴리머와 적절한 부형제를 혼합한 다음 타정하여 지속적으로 유효 약물을 방출하는 제형을 얻을 수 있다.The micronized felodipine obtained above may be mixed with a carboxyvinyl polymer for direct application as a sustained release agent and an appropriate excipient and then compressed into tablets to obtain a sustained release of the effective drug.
여기에서, 펠로디핀은 기존 제제에서의 약물 유효량인 제제 1개체당 5mg 함유되는 것이 바람직하다.Here, the felodipine is preferably contained 5mg per drug, which is a drug effective amount in the conventional formulation.
또한, 카르복시비닐 폴리머는 제제 전체중량 대비 2∼15중량% 함유되는 것이 바람직한데, 카르복시비닐 폴리머가 제제 전체중량 대비 2중량% 미만으로 함유되면 기대한 지속 방출 기준보다 매우 빠르게 약물이 방출되고, 15중량%를 초과하여 함유되면 약물의 방출속도가 너무 늦어지므로 바람직하지 않다.In addition, the carboxyvinyl polymer is preferably contained 2 to 15% by weight of the total weight of the formulation, if the carboxyvinyl polymer is contained less than 2% by weight of the total weight of the formulation, the drug is released much faster than the expected sustained release criteria, 15 If it is contained in an amount exceeding% by weight, the release rate of the drug becomes too slow, which is not preferable.
본 발명의 직타용 카르복시비닐 폴리머로는 Carbopol 71G를 사용하는 것이 바람직한데, 이는 4,000∼11,000cps의 고유점도를 갖는다.Carbopol 71G is preferably used as the carboxyvinyl polymer for direct use of the present invention, which has an inherent viscosity of 4,000 to 11,000 cps.
본 발명의 바람직한 실시예에 있어서, 본 발명의 펠로디핀 함유 지속 방출성 제제는 미분화된 입자크기 20㎛ 이내의 펠로디핀 5g에 직타용 서방성 기제로서 카르복시비닐 폴리머를 제제 전체중량 대비 2∼15중량%, 부형제로서 제제 전체중량 대비 60∼80중량%의 유당, 10∼30중량%의 인산일수소칼슘 및 0.1∼3중량%의 활택제를 혼합한 후 타정함으로써 제조될 수 있다. 유당이 제제 전체중량 대비 60중량% 미만으로 함유되면 지속방출성이 확보되지 않고, 80중량%를 초과하여 함유되면 방출이 너무 지연되므로 바람직하지 않다. 또한, 인산일수소칼슘이 제제 전체중량 대비 10중량% 미만으로 함유되면 용출이 빨라지고, 30중량%를 초과하여 함유되면 제제가 너무 커지므로 바람직하지 않다. 또한, 활택제가 제제 전체중량 대비 0.1중량% 미만으로 함유되면 제조시 스티킹(sticking) 현상이 발생하고 유동성이 불량하여 제제의 제조가 곤란하고, 3중량%를 초과하여 함유되면 제제의 지속 방출성을 저하시킬 수 있으므로 바람직하지 않다.In a preferred embodiment of the present invention, the pelodipine-containing sustained-release preparation of the present invention comprises 5 to 20 g of felodipine having a micronized particle size of 20 µm or less, and a carboxyvinyl polymer as a sustained release base for direct application, from 2 to 15 wt. %, 60 to 80% by weight lactose, 10 to 30% by weight of calcium dihydrogen phosphate and 0.1 to 3% by weight of the lubricant as a excipient can be prepared by mixing and tableting. If the lactose is contained in less than 60% by weight relative to the total weight of the formulation, sustained release is not secured, and when it contains more than 80% by weight is not preferable because the release is too delayed. In addition, when the calcium monohydrogen phosphate is contained in less than 10% by weight relative to the total weight of the preparation, the elution is faster, and if it contains more than 30% by weight, the preparation becomes too large, which is not preferable. In addition, if the lubricant is contained in less than 0.1% by weight of the total weight of the formulation, sticking phenomenon occurs during manufacturing and poor fluidity, making the formulation difficult, and if contained in more than 3% by weight sustained release of the formulation It is not preferable because it can lower.
이하, 구체적인 실시예 및 비교예를 가지고 본 발명의 구성 및 효과를 보다 상세히 설명하나, 이들 실시예는 단지 본 발명을 보다 명확하게 이해시키기 위한 것일 뿐, 본 발명의 범위를 한정하고자 하는 것은 아니다.Hereinafter, the structure and effect of the present invention will be described in more detail with specific examples and comparative examples, but these examples are only intended to more clearly understand the present invention, and are not intended to limit the scope of the present invention.
하기 실시예 및 비교예에서 사용하는 미분화된 펠로디핀은, 펠로디핀을 고속분쇄기(High Speed Mill, Fuji Paudal사, Japan)를 이용하여 수회 분쇄하여 입자크기를 입자 분석기(Microtrac S-3000, Microtrac Inc., USA)로 측정시, 20㎛ 이내의 입자가 99% 이상이 되도록 한 것이다.The micronized pelodipine used in the following examples and comparative examples is pulverized felodipine several times using a high speed mill (High Speed Mill, Fuji Paudal, Japan) to determine the particle size of the particle analyzer (Microtrac S-3000, Microtrac Inc.). , USA) to make 99% or more of particles within 20 µm.
또한, 하기 실시예 및 비교예에서 사용하는 카르복시비닐 폴리머로서는 점도 4,000∼11,000cps인 Carbopol 71G(Noveon Inc., USA)를 사용하였다.Carbopol 71G (Noveon Inc., USA) having a viscosity of 4,000 to 11,000 cps was used as the carboxyvinyl polymer used in the following examples and comparative examples.
실시예 1Example 1
미분화된 펠로디핀 5.0g, 유당(lactose) 159.0g, Carbopol 71G 11.0g, 인산일수소칼슘 40.0g, 스테아린산마그네슘 3.0g, 탈크 2.0g을 혼합한 다음, 10분간 잘 섞어 준 후 타정한다.5.0 g of undifferentiated pelodipine, 159.0 g of lactose, 11.0 g of Carbopol 71G, 40.0 g of calcium dihydrogen phosphate, 3.0 g of magnesium stearate, and 2.0 g of talc are mixed and mixed well for 10 minutes before tableting.
실시예 2Example 2
미분화된 펠로디핀 5.0g, 유당(lactose) 148.0g, Carbopol 71G 22.0g, 인산 일수소칼슘 40.0g, 스테아린산마그네슘 3.0g, 탈크 2.0g을 혼합한 다음, 10분간 잘 섞어 준 후 타정한다.5.0 g of undifferentiated pelodipine, 148.0 g of lactose, 22.0 g of Carbopol 71G, 40.0 g of calcium dihydrogen phosphate, 3.0 g of magnesium stearate, and 2.0 g of talc are mixed well, and then mixed.
실시예 3Example 3
미분화된 펠로디핀 5.0g, 유당(lactose) 165.6g, Carbopol 71G 4.4g, 인산일수소칼슘 40.0g, 스테아린산마그네슘 3.0g, 탈크 2.0g을 혼합한 다음, 10분간 잘 섞어 준 후 타정한다.5.0 g of finely divided felodipine, 165.6 g of lactose, 4.4 g of Carbopol 71G, 40.0 g of calcium dihydrogen phosphate, 3.0 g of magnesium stearate, and 2.0 g of talc are mixed and mixed well for 10 minutes before tableting.
비교예 1Comparative Example 1
미분화하지 않은 펠로디핀 5.0g, 유당(lactose) 159.0g, Carbopol 71G 11.0g, 인산일수소칼슘 40.0g, 스테아린산마그네슘 3.0g, 탈크 2.0g을 혼합한 다음, 10분간 잘 섞어 준 후 타정한다.5.0 g of undifferentiated felodipine, 159.0 g of lactose, 11.0 g of Carbopol 71G, 40.0 g of calcium dihydrogen phosphate, 3.0 g of magnesium stearate, and 2.0 g of talc are mixed well, followed by tableting.
비교예 2 Comparative Example 2
펠로디핀과 폴리비닐피롤리돈을 1 : 1의 비율로 제조한 고체 분산체 10.0g, 유당(lactose) 154.0g, Carbopol 71G 11.0g, 인산일수소칼슘 40.0g, 스테아린산마그네슘 3.0g, 탈크 2.0g을 혼합한 다음, 10분간 잘 섞어 준 후 타정한다.10.0 g of solid dispersion prepared from felodipine and polyvinylpyrrolidone in a ratio of 1: 1, lactose 154.0 g, Carbopol 71G 11.0 g, calcium dihydrogen phosphate 40.0 g, magnesium stearate 3.0 g, talc 2.0 g After mixing, mix well for 10 minutes and tableting.
비교예 3Comparative Example 3
펠로디핀과 폴리비닐피롤리돈을 1 : 1의 비율로 제조한 고체 분산체 10.0g, 유당(lactose) 130.0g, 유드라짓 RS-PO 45.0g, 인산일수소칼슘 30.0g, 스테아린산마그네슘 3.0g, 탈크 2.0g을 혼합한 다음, 10분간 잘 섞어 준 후 타정한다.10.0 g of solid dispersion prepared with felodipine and polyvinylpyrrolidone in a ratio of 1: 1, lactose 130.0 g, Eudragit RS-PO 45.0 g, calcium dihydrogen phosphate 30.0 g, magnesium stearate 3.0 g Mix 2.0 g of talc, mix well for 10 minutes, and then tablet.
실험예 1Experimental Example 1
미분화된 펠로디핀의 용해도 증가를 확인하기 위해서 실시예 1과 비교예 1 및 비교예 2에서 제조된 제형을 사용하여 각 시간별 약물 방출율(%)을 비교하였다. 약물 방출은 대한약전 일반시험법 중 용출시험법 제2법(paddle법)에 따라 시험하되, 용출액으로서 pH 6.5 인산염 완충액 500ml를 사용하여 매분 100회전의 속도로 회전시키면서 용출 시험 개시후 1시간, 4시간, 7시간후에 용출액을 취하여 대한약전 일반시험법 중 흡광도 측정법에 따라 362nm 및 450nm에서 흡광도를 측정하여 시험한다. In order to confirm the increase in solubility of the micronized felodipine, the drug release rate (%) was compared for each hour using the formulations prepared in Example 1 and Comparative Examples 1 and 2. The drug release was tested according to the Elution Test Method 2 (paddle method) of the Korean Pharmacopoeia General Test Method, using 500 ml of pH 6.5 phosphate buffer solution as the eluant, rotating at a rate of 100 revolutions per minute, 4 hours after the start of the dissolution test. After 7 hours, the eluate is taken and tested for absorbance at 362 nm and 450 nm according to the absorbance measurement method of the Korean Pharmacopoeia.
약물 방출율 시험 결과를 하기 표 및 도 1에 나타낸다.Drug release rate test results are shown in the table below and FIG. 1.
실험예 2Experimental Example 2
카르복시비닐 폴리머의 지속성 약물 방출을 확인하기 위하여 실시예 1∼3 및 비교예 3에서 제조된 제형을 사용하여 각 시간별 약물 방출율(%)을 시험하였다. 약물 방출 시험은 실험예 1과 동일한 방법으로 실시한다.To confirm sustained drug release of the carboxyvinyl polymer, the drug release rate (%) was tested for each hour using the formulations prepared in Examples 1-3 and Comparative Example 3. Drug release test is carried out in the same manner as in
약물 방출율 시험 결과를 하기 표 및 도 2에 나타낸다. Drug release rate test results are shown in the table below and FIG. 2.
본 발명에 의하면, 물에 난용성인 펠로디핀을 20㎛ 이내의 입자크기를 갖는 미세 분말로 분쇄하여 용출율을 개선하고, 여기에 직타용 서방기제로서 카르복시비닐 폴리머를 혼합하여 제제화함으로써 약물이 일정시간 동안 서서히 방출되도록 한 펠로디핀 함유 지속 방출성 제제가 제공된다. 이에 따라, 유효 약물 농도가 유지되어 치료 효과를 상승시키며 환자의 복약순응도를 높일 수 있고, 개선된 제조 공정을 확립할 수 있다.According to the present invention, the dissolution rate of the poorly soluble pelodipine into fine powder having a particle size of less than 20㎛ to improve the dissolution rate, and by mixing the carboxyvinyl polymer as a sustained-release agent for direct application to the formulation for a certain time Pelodipine-containing sustained release formulations are provided that allow for slow release. Accordingly, the effective drug concentration can be maintained to increase the therapeutic effect, to increase the patient's medication compliance, and to establish an improved manufacturing process.
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