KR100296413B1 - Sustained released tablet containing cefaclor - Google Patents
Sustained released tablet containing cefaclor Download PDFInfo
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- KR100296413B1 KR100296413B1 KR1019980011397A KR19980011397A KR100296413B1 KR 100296413 B1 KR100296413 B1 KR 100296413B1 KR 1019980011397 A KR1019980011397 A KR 1019980011397A KR 19980011397 A KR19980011397 A KR 19980011397A KR 100296413 B1 KR100296413 B1 KR 100296413B1
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
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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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0065—Forms with gastric retention, e.g. floating on gastric juice, adhering to gastric mucosa, expanding to prevent passage through the pylorus
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
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- 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
- A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
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Abstract
Description
제1도는 세파클러캅셀 375 mg (대웅릴리)과 본 발명에 따른 서방성 정제(세파클러 375mg)을 각각 비글견에 투여시 혈중 세파클러의 농도변화를 나타낸 것이다.FIG. 1 shows the change in the concentration of Sephacler in blood when 375 mg of Sepaclecapcel (Daewoong Lili) and sustained-release tablet (Sepacler 375mg) according to the present invention are administered to beagle dogs.
□ : 세파클러캅셀 375 mg (대웅릴리)투여시 혈중농도변화□: Changes in blood concentration when Sephaclocapcel 375 mg (Daewoong Lilly) is administered
◆ : 본 발명에 따른 정제(세파클러 375mg) 투여시 혈중농도변화◆: Changes in blood concentrations when tablets (Sepacller 375mg) are administered according to the present invention.
본 발명은 세파클러 함유 서방성 정제 및 그의 제조방법에 관한 것으로 더욱 상세하게는 정제 총중량에 대하여 세파클러 30 - 90 중량%, 팽윤성고분자 5 - 60중량%, 탄산수소나트륨 1- 10 중량%를 포함하는 세파클러함유 서방성 정제 및 그의 제조방법에 관한 것이다.The present invention relates to a sephacller-containing sustained-release tablet and a method for preparing the same, and more particularly, to 30-90 wt% of Sephacller, 5-60 wt% of swellable polymer, and 1-10 wt% of sodium hydrogencarbonate. It relates to a sephacller-containing sustained-release tablet and a method for producing the same.
세파클러(Cefaclor)는 상기도 감염증, 하기도 감염증, 부비강염의 보조요법, 중이염, 비뇨기계 감염증, 피부나 피부조직 감염증에 높은 치료효과를 나타내는 경구용 세팔로스포린계 항생물질로서 위나 소장상부등의 한정된 위장관 흡수부위를 가지고 있고 수용액중에서 pH가 4.5보다 작을 때는 안정하나 그 이상이 되면 쉽게 불활성화 되는 성질을 가지고 있으며, 체내의 혈중반감기는 1시간 이내로 1일 3회 간격으로 투여하여 사용되고 있다.Cefaclor is an oral cephalosporin-based antibiotic that has a high therapeutic effect on upper respiratory tract infections, lower respiratory tract infections, sinusitis adjuvant therapy, otitis media, urinary tract infections, and skin or skin tissue infections. It has a gastrointestinal tract absorption area and is stable when pH is less than 4.5 in aqueous solution, but it is easily inactivated when it is more than that. The half-life of blood in the body is used by three times a day within 1 hour.
상기 세파클러를 유효성분으로 하는 서방성제제에 관한 종래의 기술은 미국 특허 제4,713,247호(상품명:L-케플랄, 일본 시오노기사)에서 개시한 바와 같이 속방성 펠렛과 서방성 펠렛을 6:4로 함유한 캅셀제로서 위에서는 속방성 펠렛이 용해되어 약물을 방출하고, 장에서는 서방성 펠렛이 용해되어 일정속도로 약물을 흡수하도록 한 제제로 1일 2회 (2캅셀씩) 복용하여야 한다. 또한, 미국특허 제4,968,508호 (상품명:시클러 CD, 미국 릴리사)에서 개시한 바와 같이 장용성 고분자와 위용성 고분자를 서방성 기제로 사용한 매트릭스형 정제로서 위장관의 pH에 관계없이 일정한 속도로 약물이 방출하도록 설계한 제제로 역시 1일 2회 복용하여야 한다.Conventional techniques related to sustained-release preparations using the Sephacller as active ingredients are disclosed in U.S. Patent No. 4,713,247 (trade name: L-Kepral). (Siono, Japan) as a capsule containing rapid release pellets and sustained release pellets at 6: 4, the rapid release pellets dissolve in the stomach to release the drug, and the sustained release pellets dissolve in the intestine at a constant rate. The drug should be taken twice a day (2 capsules) to absorb the drug. In addition, U.S. Patent No. 4,968,508 (trade name: Cycler CD) , Lilly, USA), a matrix-type tablet using enteric and gastric polymers as a sustained release base, and should be taken twice daily as a drug designed to release the drug at a constant rate regardless of the pH of the gastrointestinal tract. do.
그러나, 미국특허 제4,713,247호 및 미국특허 제4,968,508호에서 개시한 서방성 제제는 모두 1일 2회를 복용하는 제제로서 가장 이상적인 투여방법인 1일 1회투여(once-a-day appilication)로 서방화시킬 수 없는 문제점을 가지고 있다. 즉, 상기 종래의 서방성 제제는 단지 일정한 속도로만 약물(세파클러)을 방출하도록 설계되어 있기 때문에 1일 1회투여 형태로 서방화시키기 위하여는 다량의 세파클러를 사용할 수밖에 없으며, 이는 초기의 혈중농도를 과도하게 증가시켜 부작용이 발생할 우려가 있다.However, the sustained release formulations disclosed in U.S. Patent No. 4,713,247 and U.S. Patent No. 4,968,508 are all taken twice daily, and are sustained by once-a-day appilication. There is a problem that cannot be harmonized. That is, since the conventional sustained-release preparation is designed to release the drug (sepacller) only at a constant rate, a large amount of sefackler has to be used to sustain the sustained release in a daily dosage form. Too much concentration can cause side effects.
이에, 본 발명자는 1일 1회만 투여함에도 불구하고 지속적으로 혈중농도를 유지시킬 수 있는 새로운 세파클러함유 서방성 제제를 개발하고자 연구를 거듭한 결과, 정제 총중량에 대하여 세파클러 30 - 90 중량%, 팽윤성고분자 5 - 60 중량%, 탄산수소나트륨 1- 10 중량%를 포함하여 세파클러함유 서방성 정제를 제조하여 투여하였을 때, 1일 2회 투여제제 뿐 아니라 1일 1회투여도 가능한 서방성 제제를 제조할 수 있다는 것을 발견하여 본 발명을 완성하게 되었다.Thus, the present inventors conducted a study to develop a new Sephacller-containing sustained-release formulation that can maintain blood levels continuously even after administration only once a day, Separcler 30-90% by weight, based on the total weight of the tablet, Sustained-release formulations that can be administered once a day as well as twice-daily formulations when prepared and administered as a sephacller-containing sustained-release tablet containing 5 to 60% by weight of swellable polymer and 1 to 10% by weight of sodium hydrogencarbonate It has been found that the present invention can be completed to complete the present invention.
즉, 본 발명에 따른 정제는 경구투여후 위액과 접촉하여 반응함으로써 기포를 발생시키게 되어 제제의 밀도가 위액의 비중보다 작게되어 위액중에 부유된 후 팽윤성고분자의 팽윤으로 정제 내부의 세파클러가 서서히 방출되도록 설계된 서방성 제제이며, 팽윤성고분자 및 탄산수소나트륨의 함량을 조절함으로써 주약인 세파클러의 방출속도를 조절할 수 있는 장점이 있다.That is, the tablet according to the present invention generates bubbles by contact with gastric juice after oral administration, and the density of the preparation is smaller than the specific gravity of the gastric juice so that it is suspended in gastric juice and then swelling of the swellable polymer is gradually released into the tablet. It is designed to be a sustained release formulation, and by controlling the content of the swellable polymer and sodium bicarbonate, there is an advantage of controlling the release rate of the Sephacl.
이하, 본 발명을 상세히 설명한다.Hereinafter, the present invention will be described in detail.
본 발명은 정제 총중량에 대하여 세파클러 30 - 90 중량%, 팽윤성고분자 50 - 60 중량%, 탄산수소나트륨 1- 10 중량%를 포함하는 세파클러함유 서방성 정제를 제공하는 것을 목적으로 한다.An object of the present invention is to provide a sephacller-containing sustained-release tablet containing 30 to 90% by weight of sephackler, 50 to 60% by weight of swellable polymer, and 1 to 10% by weight of sodium hydrogencarbonate.
또한, 본 발명의 목적은 상기 정제의 제조방법을 제공하는 것을 포함한다.It is also an object of the present invention to provide a method for producing the tablet.
이하, 본 발명을 더욱 상세히 설명한다.Hereinafter, the present invention will be described in more detail.
본 발명에 따른 정제에 주약으로 사용된 세파클러는 정제 총중량에 대하여 30 - 90 중량%가 바람직하고, 제제의 크기를 고려할 때 60%이상 함유하는 것이 더욱 바람직하다.Sephacller used as a drug in the tablet according to the present invention is preferably 30 to 90% by weight based on the total weight of the tablet, more preferably 60% or more in consideration of the size of the preparation.
본 발명에 따른 정제에 함유된 탄산수소나트륨은 기포발생제로서 정제 총중량에 대하여 1 - 10 중량%로 사용하는 것이 바람직하고 1 - 5 중량%로 사용하는 것이 더욱 바람직하다. 탄산수소나트륨의 함량이 너무 많을 경우 기포량의 발생이 많기 때문에 위에 자극을 줄 수 있고, 정제가 붕해되거나 서방성을 상실할 수 있다.The sodium hydrogen carbonate contained in the tablet according to the present invention is preferably used in an amount of 1 to 10% by weight and more preferably in an amount of 1 to 5% by weight based on the total weight of the tablet as the bubble generator. If the content of sodium bicarbonate is too high, the amount of bubbles is generated a lot, it may irritate the stomach, the tablet may disintegrate or lose the sustained release.
또한, 본 발명에 따른 정제는 기포발생보조제로 구연산, 주석산, 사과산등과같은 유기산을 포함시켜 음식물의 섭취로 인한 일시적인 위내 pH상승으로 인하여 발생할 수 있는 문제점을 방지할 수 있다. 또한, 본 발명에 따른 정제는 기포발생완충제로서 탄산칼슘 또는 탄산마그네슘을 포함시켜 과도한 기포발생에 따른 붕해발생을 방지할 수 있다.In addition, the tablet according to the present invention can prevent problems that may occur due to a temporary increase in the pH of the stomach due to food intake by including organic acids such as citric acid, tartaric acid, malic acid as a bubble generating aid. In addition, the tablet according to the present invention may include calcium carbonate or magnesium carbonate as a bubble generating buffer to prevent the disintegration caused by excessive foaming.
본 발명에 따른 정제에 함유되는 팽윤성고분자로는 하이드록시프로필셀룰로오스, 하이드록시프로필메틸셀룰로오스, 카복시메틸셀룰로스 나트륨, 폴리비닐피롤리돈, 알긴산 나트륨등이 바람직하며, 이중 하이드록시프로필메틸셀룰로오스 또는 카복시메틸셀룰로스 나트륨이 가장 바람직하다. 본 발명에 따른 정제에 함유되는 팽윤성고분자의 함량은 정제 총중량에 대하여 5 - 60 중량%가 바람직하며, 팽윤성고분자의 함량을 조절함으로써 효과적으로 주약인 세파클러의 방출속도를 변화시킬 수 있다. 즉, 팽윤성고분자의 함량이 높을수록 세파클러의 방출속도는 지연되며, 함량이 낮을수록 세파클러의 방출속도는 빠르게 된다.The swellable polymers contained in the tablets according to the present invention are preferably hydroxypropyl cellulose, hydroxypropyl methyl cellulose, carboxymethyl cellulose sodium, polyvinylpyrrolidone, sodium alginate, and the like, of which hydroxypropyl methyl cellulose or carboxymethyl Sodium cellulose is most preferred. The content of the swellable polymer contained in the tablet according to the present invention is preferably 5 to 60% by weight based on the total weight of the tablet, and by controlling the content of the swellable polymer, it is possible to effectively change the release rate of the Sephacl. In other words, the higher the content of the swellable polymer, the slower the release rate of the sepacller, the lower the content, the faster the release rate of the sepacller.
본 발명에 따른 정제는 약제학분야에서 공지되어 사용가능한 부형제를 함유하여 제제화할 수 있다. 본 발명에 따른 정제에 포함될 수 있는 부형제로는 미세결정성 셀룰로오스, 팩틴, 알긴산 나트륨, 키토산, 하이드록시프로필메틸셀룰로오스 프탈레이트, 셀룰로오스아세테이트 프탈레이트, 하이드록시프로필메틸셀룰로오스아세테이트 숙시네이트, 셀룰로오스아세테이트 트리멜리테이트, 젤라틴, 백당, 락토스, 만니톨, 에틸셀룰로스, 마그네슘 알루미늄 실리케이트와 같은 천연 또는 완전 합성 또는 부분 합성된 친수성 고무등이 있다.Tablets according to the invention may be formulated containing excipients known and available in the pharmaceutical art. Excipients that may be included in the tablets according to the invention include microcrystalline cellulose, pectin, sodium alginate, chitosan, hydroxypropylmethylcellulose phthalate, cellulose acetate phthalate, hydroxypropylmethylcellulose acetate succinate, cellulose acetate trimellitate, Natural or fully synthetic or partially synthesized hydrophilic rubbers such as gelatin, sucrose, lactose, mannitol, ethylcellulose, magnesium aluminum silicate and the like.
본 발명은 상기 성분들이 포함된 서방성 정제의 제조방법을 포함한다. 본 발명에 따른 서방성 정제의 제조방법은 통상의 습식과립법에 따라 상기 성분을 혼합하여 과립을 제조한 후, 공지의 활택제와 혼합하여 타정하여 제조할 수도 있으나, 초기부유시간을 최소화하여 부유상태에서 세파클러를 서서히 방출시키기 위하여는 세파클러 및 부형제를 일부의 팽윤성고분자와 탄산수소나트륨과 혼합하여 과립을 제조한 다음, 나머지 팽윤성고분자 및 탄산수소나트륨을 활택제와 함께 과립과 다시 혼합·타정하여 제조하는 것이 바람직하다. 여기서 활택제로는 약제학분야에서 공지되어 사용가능한 활택제, 예를들면, 스테아린산, 마그네슘 스테아레이트, 에어로질TM등을 사용할 수 있다. 또한, 과립내에 포함되는 기포발생제(탄산수소나트륨)는 총함량중 10∼90 중량%가 바람직하고, 50%이상으로 사용하는 것이 더욱 바람직하다.The present invention includes a method for producing a sustained release tablet containing the above components. The method for preparing a sustained release tablet according to the present invention may be prepared by mixing the above components according to a conventional wet granulation method, preparing granules by mixing them with a known lubricant, but minimizing initial flotation time. In order to release the Sephacle slowly in the state, the granules are prepared by mixing the Sepacle and the excipient with some swellable polymer and sodium hydrogen carbonate, and then mixing the remaining swellable polymer and sodium hydrogen carbonate together with the lubricant and the granule again. It is preferable to prepare accordingly. The glidants may be used glidants known and used in the pharmaceutical field, such as stearic acid, magnesium stearate, aerosol TM and the like. In addition, the bubble generator (sodium bicarbonate) contained in the granules is preferably 10 to 90% by weight, more preferably 50% or more of the total content.
상기 제조방법에 있어서, 기포발생보조제 및 기포발생완충제를 포함하여 서방성 정제를 제조할 경우, 구연산, 주석산, 사과산등의 기포발생보조제는 과립제조시 혼합하는 것이 바람직하며, 탄산칼슘 또는 탄산마그네슘등의 기포발생완충제는 과립 제조시 및 타정시로 나누어 혼합하는 것이 바람직하다.In the above production method, when preparing a sustained-release tablet including a bubble generating aid and a bubble generating buffer, it is preferable to mix the bubble generating auxiliary such as citric acid, tartaric acid, malic acid when preparing granules, calcium carbonate or magnesium carbonate It is preferable to mix the bubble-forming buffer of dividing into granules and tableting.
상기와 같이 제조한 본 발명에 따른 정제는 하기 실시예에서 확인할 수 있는 바와 같이 세파클러의 방출속도를 임의로 조절할 수 있어,1일 2회투여 정제 뿐 아니라 1일 1회투여도 가능하도록 설계할 수 있다.Tablets according to the present invention prepared as described above can be arbitrarily adjusted the release rate of the sepacller as can be seen in the following examples, it can be designed to be administered not only twice a day tablets but also once a day. have.
[실시예 1]Example 1
세파클러 400g, 하이드록시프로필메틸셀룰로오스 20g, 탄산칼슘 20g, 탄산수소나트륨 10g, 구연산 10g, 하이드록시프로필메틸셀룰로오스 프탈레이트 10g, 에어로질 2g를 혼합한 후 70%에탄올 용액 140 ml로 제립한 다음, 40℃에서 수분함량이 3% 이하가 될 때까지 건조하여 건조과립을 제조한 후 정립(14호 mesh)하였다. 정립한 건조과립을 하이드록시프로필메틸셀룰로오스 60g, 탄산칼슘 20g, 탄산수소나트륨5g, 및 카복시메틸셀룰로오스 나트륨 30g과 혼합한 다음, 40호 메쉬체로 통과시킨 에어로질 1g, 마그네슘 스테아레이트 3g을 다시 혼합한후 압축 타정기로 타정하여 정제를 제조하였다.Sepacle 400g, 20g of hydroxypropylmethylcellulose, 20g of calcium carbonate, 10g of sodium bicarbonate, 10g of citric acid, 10g of hydroxypropylmethylcellulose phthalate, and 2g of aerosol were granulated with 140 ml of 70% ethanol solution, and then 40 The dried granules were dried by drying until the moisture content was 3% or less at 占 폚, and then sieved (No. 14 mesh). The granulated granules were mixed with 60 g of hydroxypropyl methyl cellulose, 20 g of calcium carbonate, 5 g of sodium bicarbonate, and 30 g of sodium carboxymethyl cellulose, followed by mixing 1 g of aerosol passed through a No. 40 mesh sieve and 3 g of magnesium stearate. After tableting with a compressed tablet press to prepare a tablet.
상기에서 제조한 정제를 인공위액에 넣었을 때 투여후 약 10초 이내에 바로 부유하여 6시간 이상을 액의 상층부에 떠 있었다.When the above-prepared tablets were placed in artificial gastric juice, they were immediately suspended within about 10 seconds after the administration, and floated in the upper layer of the liquid for 6 hours or more.
또한, 상기에서 제조한 정제를 37℃의 조건하에서 0.1N 염산시액 900㎖을 사용하여 대한약전 용출시험 제2법에 따라 시험하였을 때 그 결과는 다음 표1과 같다.In addition, when the tablet prepared above was tested according to the Korean Pharmacopoeia Elution Test No. 2 using 900 ml of 0.1 N hydrochloric acid solution at 37 ° C., the results are shown in Table 1 below.
[표 1]TABLE 1
[실시예 2]Example 2
세파클러 393g, 하이드록시프로필메틸셀룰로오스 20g, 탄산칼슘 20g, 탄산수소나트륨 10g, 구연산 10g, 하이드록시프로필메틸셀룰로오스 프탈레이트 10g을 혼합한 후 70% 에탄올 용액 140 ml 제립한 다음, 40℃에서 수분함량이 3% 이하가 될때까지 건조하여 건조과립을 제조한 후 정립(16 mesh)하였다. 정립한 건조과립을 하이드록시프로필메틸셀룰로오스 80g, 탄산칼슘20g, 탄산수소나트륨 5g, 및 미세결정 셀룰로오스 25g과 혼합한 다음, 30호 메시체로 통과시킨 마그네슘 스테아레이트 6g을 다시 혼합한 후 압축타정기로 타정하여 정제를 제조하였다.Sepacle 393g, 20g of hydroxypropylmethylcellulose, 20g of calcium carbonate, 10g of sodium bicarbonate, 10g of citric acid, 10g of hydroxypropylmethylcellulose phthalate, 140 ml of 70% ethanol solution was granulated, and the water content at 40 ° C. It was dried until it became 3% or less to prepare dry granules, and then sieved (16 mesh). The granulated dry granules were mixed with 80 g of hydroxypropyl methyl cellulose, 20 g of calcium carbonate, 5 g of sodium bicarbonate, and 25 g of microcrystalline cellulose. Then, 6 g of magnesium stearate passed through No. 30 mesh was mixed again, followed by compression tableting. Tablets were prepared.
상기에서 제조한 정제를 인공위액에 넣었을 때 투여직후 바로 부유하여 6시간 이상을 액의 상층부에 떠 있었다.When the above-prepared tablets were placed in artificial gastric juice, they were suspended immediately after administration and floated at the upper layer of the liquid for at least 6 hours.
상기에서 제조한 정제를 실시예1과 동일한 방법으로 용출시험을 하였을 때, 그 결과는 다음 표2와 같다.When the dissolution test was carried out in the same manner as in Example 1 with the tablet prepared above, the results are shown in Table 2 below.
[표 2]TABLE 2
[실시예 3]Example 3
세파클러 393g, 하이드록시프로필메틸셀룰로오스 20g, 탄산칼슘 20g, 탄산수소나트륨 10g, 구연산 10g을 혼합한 후, 하이드록시프로필메틸셀룰로오스 프탈레이트 10g을 95% 에탄올 용액 120 ml에 용해시킨 용액으로 제립한 다음, 40℃에서 수분함량이 3% 이하가 될 때까지 건조하여 건조과립을 제조한 후 정립(16 mesh)하였다. 정립한 건조과립을 하이드록시프로필메틸셀룰로오스 70g, 탄산칼슘 15g, 탄산수소나트륨 15g, 및 미세결정 셀룰로오스 31g과 혼합한 다음, 40호 메시체로 통과시킨에어로질 3g 및 마그네슘 스테아레이트 3g을 다시 혼합한 후 압축타정기로 타정하여 정제를 제조하였다.Sepacle 393g, 20g of hydroxypropylmethylcellulose, 20g of calcium carbonate, 10g of sodium bicarbonate, 10g of citric acid were mixed, and then, 10g of hydroxypropylmethylcellulose phthalate was dissolved in 120 ml of 95% ethanol solution, and then granulated. The dried granules were dried at 40 ° C. until the water content was 3% or less, and then granulated (16 mesh). The granulated granules were mixed with 70 g of hydroxypropylmethyl cellulose, 15 g of calcium carbonate, 15 g of sodium bicarbonate, and 31 g of microcrystalline cellulose, and then again mixed with 3 g of aerosol and 3 g of magnesium stearate passed through a No. 40 mesh. Tablets were prepared by compression using a compression tablet.
상기에서 제조한 정제를 인공위액에 넣었을 때 투여후 약 30초 이내에 부유하여 6시간 이상을 액의 상층부에 떠 있었다.When the above-prepared tablets were placed in artificial gastric juice, they were floated within about 30 seconds after administration and floated at the upper layer of the liquid for at least 6 hours.
상기에서 제조한 정제를 실시예1과 동일한 방법으로 용출시험을 하였을 때, 그 결과는 다음 표3과 같다.When the dissolution test was carried out in the same manner as in Example 1 with the tablet prepared above, the results are shown in Table 3 below.
[표 3]TABLE 3
[실시예 4]Example 4
세파클러 400g, 하이드록시프로필메틸셀룰로오스 20g, 탄산칼슘 20g, 탄산수소나트륨 10g, 구연산 10g, 에어로질 1g를 혼합한 후, 하이드록시프로필메틸셀룰로오스 프탈레이트 10g을 95%에탄올 용액 120 ml 에 용해시킨 용액으로 제립한 다음, 40℃ 에서 수분함량이 3% 이하가 될 때까지 건조하여 건조과립을 제조한 후 정립(16호 mesh)하였다. 정립한 건조과립을 하이드록시프로필메틸셀룰로오스 70g, 탄산칼슘 20g, 탄산수소나트륨 5g, 및 미세결정 셀룰로오스 40g과 혼합한 다음, 30호 메쉬체로 통과시킨 에어로질 2g, 마그네슘 스테아레이트 3g을 다시 혼합한후 압축 타정기로 타정하여 정제를 제조하였다.Sepacle 400g, 20g of hydroxypropylmethylcellulose, 20g of calcium carbonate, 10g of sodium bicarbonate, 10g of citric acid and 1g of aerosol were mixed, and then 10g of hydroxypropylmethylcellulose phthalate was dissolved in 120 ml of 95% ethanol solution. After granulation, the dried granules were dried at 40 ° C. until the water content was 3% or less, and then granulated (No. 16 mesh). The granulated granules were mixed with 70 g of hydroxypropyl methyl cellulose, 20 g of calcium carbonate, 5 g of sodium bicarbonate, and 40 g of microcrystalline cellulose, and then again mixed with 2 g of aerosol and 3 g of magnesium stearate passed through a No. 30 mesh sieve. Tablets were prepared by compression using a compression tablet press.
상기에서 제조한 정제를 인공위액에 넣었을 때 투여후 약 30초 이내에 부유하여 5시간 이상을 액의 상층부에 떠 있었다.When the above-prepared tablets were placed in artificial gastric juice, they were suspended within about 30 seconds after administration and floated at the upper layer of the liquid for at least 5 hours.
상기에서 제조한 정제를 실시예1과 동일한 방법으로 용출시험을 하였을 때, 그 결과는 다음 표4와 같다.When the dissolution test was carried out in the same manner as in Example 1 with the tablet prepared above, the results are shown in Table 4 below.
[표 4]TABLE 4
[실시예 5]Example 5
세파클러 393g, 하이드록시프로필메틸셀룰로오스 110g, 탄산칼슘 20g, 탄산수소나트륨 5g, 구연산 10g을 혼합한 후, 하이드록시프로필메틸셀룰로오스 프탈레이트10g을 70% 에탄올 용액 160g에 용해시킨 용액으로 제립한 다음, 35℃에서 수분함량이 3% 이하가 될 때까지 건조하여 건조과립을 제조한 후 정립(16 mesh)하였다. 정립한 건조과립을 하이드록시프로필메틸셀룰로오스 10g, 탄산수소나트륨 2g, 및 미세결정 셀룰로오스 43g과 혼합한 다음, 40호 메시체로 통과시킨 에어로질 3g 및 마그네슘 스테아레이트 6g을 다시 혼합한 후 압축타정기로 타정하여 정제를 제조하였다.Sepacle 393g, hydroxypropylmethylcellulose 110g, calcium carbonate 20g, sodium hydrogencarbonate 5g, citric acid 10g was mixed, granulated with a solution of 10g hydroxypropylmethylcellulose phthalate dissolved in 160g 70% ethanol solution, 35 The dried granules were dried until the water content was 3% or less at 0 ° C., and then granulated (16 mesh). The dry granulated granules were mixed with 10 g of hydroxypropyl methyl cellulose, 2 g of sodium bicarbonate, and 43 g of microcrystalline cellulose, and then again mixed with 3 g of aerosol and 6 g of magnesium stearate passed through a No. 40 mesh sieve, followed by compression tableting. Tablets were prepared.
상기에서 제조한 정제를 인공위액에 넣었을 때 투여후 약 30초 이내에 부유하여 10시간 이상을 액의 상층부에 떠 있었다.When the above-prepared tablets were placed in artificial gastric juice, they were floated within about 30 seconds after administration and floated at the upper layer of the liquid for at least 10 hours.
상기에서 제조한 정제를 실시예1과 동일한 방법으로 용출시험을 하였을 때, 그 결과는 다음 표5와 같다.When the dissolution test was carried out in the same manner as in Example 1 with the tablet prepared above, the results are shown in Table 5 below.
[표 5]TABLE 5
[실시예 6]Example 6
세파클러 393g, 하이드록시프로필메틸셀룰로오스 20g, 탄산칼슘 20g, 탄산수소나트륨 10g, 구연산 10g을 혼합한 후, 하이드록시프로필메틸셀룰로오스 프탈레이트 10g을 95% 에탄올 용액 140 ml에 용해시킨 용액으로 제립한 다음, 40℃에서 수분함량이 3% 이하가 될 때까지 건조하여 건조과립을 제조한 후 정립(16 mesh)하였다. 정립한 건조과립을 하이드록시프로필메틸셀룰로오스 60g, 탄산수소나트륨 10g, 탄산칼슘 20g 및 미세결정 셀룰로오스 31g과 혼합한 다음, 30호 메시체로 통과시킨 에어로질 3g 및 마그네슘 스테아레이트 3g을 다시 혼합한 후 압축타정기로 타정하여 정제를 제조하였다.Sepacle 393g, 20g of hydroxypropylmethylcellulose, 20g of calcium carbonate, 10g of sodium bicarbonate, 10g of citric acid were mixed, and then 10g of hydroxypropylmethylcellulose phthalate was dissolved in 140 ml of 95% ethanol solution. The dried granules were dried at 40 ° C. until the water content was 3% or less, and then granulated (16 mesh). The granulated granules were mixed with 60 g of hydroxypropyl methyl cellulose, 10 g of sodium bicarbonate, 20 g of calcium carbonate, and 31 g of microcrystalline cellulose. Then, 3 g of aerosil and 3 g of magnesium stearate passed through No. 30 mesh were mixed again and then compressed. Tablets were prepared by tableting with a tablet press.
상기에서 제조한 정제를 인공위액에 넣었을 때 투여후 약 30초 이내에 부유하여 6시간 이상을 액의 상층부에 떠 있었다.When the above-prepared tablets were placed in artificial gastric juice, they were floated within about 30 seconds after administration and floated at the upper layer of the liquid for at least 6 hours.
상기에서 제조한 정제를 실시예1과 동일한 방법으로 용출시험을 하였을 때, 그 결과는 다음 표6과 같다.When the dissolution test was carried out in the same manner as in Example 1 with the tablet prepared above, the results are shown in Table 6 below.
[표 6]TABLE 6
[실시예 7]Example 7
세파클러 393g, 하이드록시프로필메틸셀룰로오스 200g, 탄산칼슘 20g, 탄산수소나트륨 10g, 구연산 10g을 혼합한 후, 하이드록시프로필메틸셀룰로오스 프탈레이트 10g을 70% 에탄올 용액 160g에 용해시킨 용액으로 제립한 다음, 35℃에서 수분 함량이 3% 이하가 될 때까지 건조하여 건조과립을 제조한 후 정립(16 mesh)하였다. 정립한 건조과립을 하이드록시프로필메틸셀룰로오스 20g, 탄산수소나트륨 2g, 및 미세결정 셀룰로오스 43g과 혼합한 다음, 40호 메시체로 통과시킨 에어로질 3g 및 마그네슘 스테아레이트 6g을 다시 혼합한 후 압축타정기로 타정하여 정제를 제조하였다.Sepacle 393g, 200g of hydroxypropylmethylcellulose, 20g of calcium carbonate, 10g of sodium bicarbonate, 10g of citric acid were mixed, and then granulated with a solution of 10g of hydroxypropylmethylcellulose phthalate dissolved in 160g of 70% ethanol solution, and then 35 The dried granules were prepared by drying until the moisture content was 3% or less at 0 ° C., followed by sizing (16 mesh). The dry granulated granules were mixed with 20 g of hydroxypropylmethyl cellulose, 2 g of sodium bicarbonate, and 43 g of microcrystalline cellulose, and then again mixed with 3 g of aerosol and 6 g of magnesium stearate passed through a No. 40 mesh sieve, and then pressed with a compression tablet. Tablets were prepared.
상기에서 제조한 정제를 인공위액에 넣었을 때 투여후 약 30초 이내에 부유하여 10시간 이상을 액의 상층부에 떠 있었다.When the above-prepared tablets were placed in artificial gastric juice, they were floated within about 30 seconds after administration and floated at the upper layer of the liquid for at least 10 hours.
상기에서 제조한 정제를 실시예1과 동일한 방법으로 용출시험을 하였을 때,그 결과는 다음 표7와 같다.When the dissolution test was carried out in the same manner as in Example 1 with the tablet prepared above, the results are shown in Table 7 below.
[표 7]TABLE 7
[시험예 1][Test Example 1]
12시간 단식시킨 비글견에 실시예 4에서 제조한 정제(세파클러 375mg)와 세파클러캅셀 375mg (대웅릴리)을 200㎖의 정제수와 같이 복용시킨 후 투여전, 투여후 30분, 1시간, 2시간, 3시간, 4시간, 6시간, 8시간, 10시간, 12시간 마다 1.5㎖의 혈액을 채취하여 3000 r.p.m으로 원심분리하고, 메탄올로 추출하여 고속 액체크로마토그래피로 세파클러의 농도를 분석하였으며, 그 결과는 제1도와 같다.Beagle dogs fasted for 12 hours were taken the tablets (Sepacller 375mg) and Sephaclercapcel 375mg (Daewoongli) prepared in Example 4 with 200ml of purified water, and then, 30 minutes, 1 hour, 2 hours after administration. Every 1.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, and 12 hours, 1.5 ml of blood was collected, centrifuged at 3000 rpm, extracted with methanol, and the Sepacle concentration was analyzed by high-performance liquid chromatography. , And the result is shown in FIG.
제1도에서 확인할 수 있는 바와 같이 본 발명에 따라 설계한 정제로부터 세파클러의 용출패턴이 전형적인 서방성 정제의 패턴을 나타내고 있다.As can be seen in FIG. 1, the elution pattern of Sephacller from the tablet designed according to the present invention shows a pattern of a typical sustained release tablet.
Claims (1)
Priority Applications (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1019980011397A KR100296413B1 (en) | 1998-04-01 | 1998-04-01 | Sustained released tablet containing cefaclor |
| EP99912140A EP1067937A1 (en) | 1998-04-01 | 1999-04-01 | Sustained-release composition containing cefaclor |
| AU30572/99A AU3057299A (en) | 1998-04-01 | 1999-04-01 | Sustained-release composition containing cefaclor |
| JP2000540831A JP2002509887A (en) | 1998-04-01 | 1999-04-01 | Cefaclor-containing sustained release composition |
| CNB998068233A CN1151791C (en) | 1998-04-01 | 1999-04-01 | Sustained-release composition containing cefaclor |
| PCT/KR1999/000159 WO1999049868A1 (en) | 1998-04-01 | 1999-04-01 | Sustained-release composition containing cefaclor |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1019980011397A KR100296413B1 (en) | 1998-04-01 | 1998-04-01 | Sustained released tablet containing cefaclor |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR19990079034A KR19990079034A (en) | 1999-11-05 |
| KR100296413B1 true KR100296413B1 (en) | 2001-11-14 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1019980011397A KR100296413B1 (en) | 1998-04-01 | 1998-04-01 | Sustained released tablet containing cefaclor |
Country Status (6)
| Country | Link |
|---|---|
| EP (1) | EP1067937A1 (en) |
| JP (1) | JP2002509887A (en) |
| KR (1) | KR100296413B1 (en) |
| CN (1) | CN1151791C (en) |
| AU (1) | AU3057299A (en) |
| WO (1) | WO1999049868A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012169677A1 (en) * | 2011-06-09 | 2012-12-13 | 주식회사 비씨월드제약 | Composition for controlling gastric retention and release |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
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| IT1318495B1 (en) * | 2000-05-04 | 2003-08-25 | Lisapharma Spa | PHARMACEUTICAL FORMULATIONS, WITH MODIFIED RELEASE, WITH HIGH AVAILABILITY, CONTAINING ACTIVE INGREDIENTS IN ACTIVITIES |
| EP2263654B1 (en) | 2000-06-21 | 2012-10-10 | Cubist Pharmaceuticals, Inc. | Compositions for improving the oral absorption of antimicrobial agents |
| US7527807B2 (en) | 2000-06-21 | 2009-05-05 | Cubist Pharmaceuticals, Inc. | Compositions and methods for increasing the oral absorption of antimicrobials |
| KR20040043589A (en) * | 2002-11-19 | 2004-05-24 | 경동제약 주식회사 | Slow releasable drugs containing cefarclor as a effective ingredient and preparing method thereof |
| US7919483B2 (en) * | 2005-06-24 | 2011-04-05 | Medicis Pharmaceutical Corporation | Method for the treatment of acne |
| US8722650B1 (en) | 2005-06-24 | 2014-05-13 | Medicis Pharmaceutical Corporation | Extended-release minocycline dosage forms |
| KR100683193B1 (en) * | 2005-07-30 | 2007-02-15 | 주식회사유한양행 | Processes for preparing a diclazuril-containing pharmaceutical composition |
| TR201000688A2 (en) | 2010-01-29 | 2011-08-22 | B�Lg�� Mahmut | Effervescent formulations containing cefaclor and clavulanic acid as active ingredient. |
| EP2361615A1 (en) * | 2010-02-19 | 2011-08-31 | Alfred E. Tiefenbacher GmbH & Co. KG | Dipyridamole prolonged-release tablet |
| US9561241B1 (en) | 2011-06-28 | 2017-02-07 | Medicis Pharmaceutical Corporation | Gastroretentive dosage forms for minocycline |
| EP3031847A1 (en) * | 2014-12-11 | 2016-06-15 | Solvay Acetow GmbH | Polymer composition comprising basic additive, process and articles comprising said polymer composition |
| CN104688701A (en) * | 2015-03-20 | 2015-06-10 | 江苏亚邦强生药业有限公司 | Cefaclor tablet and preparation method thereof |
| CN114097939B (en) * | 2021-11-19 | 2024-04-16 | 上海佩格医院管理有限公司 | Sustained release tablet matrix and preparation method and application thereof |
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|---|---|---|---|---|
| JPS601128A (en) * | 1983-06-15 | 1985-01-07 | Shionogi & Co Ltd | Long-acting cefaclor preparation |
| JPS62195323A (en) * | 1986-02-24 | 1987-08-28 | Eisai Co Ltd | Gastric resident particle |
| CA1316110C (en) * | 1987-02-27 | 1993-04-13 | Peter Lloyd Oren | Sustained release matrix formulations |
-
1998
- 1998-04-01 KR KR1019980011397A patent/KR100296413B1/en not_active IP Right Cessation
-
1999
- 1999-04-01 CN CNB998068233A patent/CN1151791C/en not_active Expired - Fee Related
- 1999-04-01 EP EP99912140A patent/EP1067937A1/en not_active Withdrawn
- 1999-04-01 AU AU30572/99A patent/AU3057299A/en not_active Abandoned
- 1999-04-01 JP JP2000540831A patent/JP2002509887A/en active Pending
- 1999-04-01 WO PCT/KR1999/000159 patent/WO1999049868A1/en not_active Application Discontinuation
Non-Patent Citations (1)
| Title |
|---|
| Chem. Pharm. Bull. 40(2): 463-6 (1992 ) * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012169677A1 (en) * | 2011-06-09 | 2012-12-13 | 주식회사 비씨월드제약 | Composition for controlling gastric retention and release |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1303291A (en) | 2001-07-11 |
| EP1067937A1 (en) | 2001-01-17 |
| AU3057299A (en) | 1999-10-18 |
| WO1999049868A1 (en) | 1999-10-07 |
| CN1151791C (en) | 2004-06-02 |
| KR19990079034A (en) | 1999-11-05 |
| JP2002509887A (en) | 2002-04-02 |
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