Journal of the Korea Academia-Industrial cooperation Society (한국산학기술학회논문지)

The Korea Academia-Industrial cooperation Society (한국산학기술학회)
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Design of swelling gastroretentive drug delivery system for sustained release of metformin

메트포르민의 서방출을 위한 팽윤성 위체류 약물전달시스템 설계

  • Weon, Kwon Yeon (College of Pharmacy, Daegu Catholic University) ;
  • Kim, Se Gie (Department of Pharmaceutical Engineering, Daegu Catholic University)
  • 원권연 (대구가톨릭대학교 약학대학) ;
  • 김세기 (대구가톨릭대학교 제약공학과)
  • Received : 2019.11.06
  • Accepted : 2020.03.06
  • Published : 2020.03.31
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Abstract

Metformin is a recommended first-line therapy drug for type 2 diabetes patients. However, compared to other oral antidiabetic drugs (OAD), metformin has a large unit dosage, with bioavailability of 40-60%. This limiting bioavailability is because metformin is absorbed only in the upper gastrointestinal tract as a BCS class 3 drug. Hence, we propose that applying the Gastroretentive Drug Delivery System (GRDDS) and extending drug release time in the stomach will result in improved bioavailability. We selected the swelling type delivery system, as it is considered the most stable gastroretention technology compared to other GRDDSs. We modified the swelling excipient by using a natural swelling excipient to form a swelling tablet made of carrageenan and hydroxypropyl methylcellulose (HPMC). Our results indicate that the swelling complex tablet made of carrageenan and HPMC has a good swelling ability and shows required sustained release in a dissolution pattern. In addition, the carrageenan complex has a better swelling ability than the marketed metformin tablet, as determined by the ratio, (swelling ability)/(excipient weight). Taken together, our results indicate that the carrageenan complex can be developed as a good swelling excipient. Further optimizations are required for the commercialization of the carrageenan complex.

메트포르민은 제2형 당뇨병의 1차 치료제로 사용되는 약물로 다른 당뇨병 치료제에 비해 투여 용량이 크고 용해도는 높으나 위장관 투과도가 낮은 특성을 갖고 있으며 주로 위장관 상부에서만 흡수되는 이유로 생체이용률이 40~60%로 낮은 편이다. 따라서 본 연구를 통해 위체류 약물전달시스템을 적용하여 제제가 위에 머무르는 시간을 증가시키고 제제로부터 방출된 약물을 서서히 소장으로 이동시킨다면 생체이용률을 증가시킬 수 있을 것으로 기대된다. 팽윤성 시스템은 다른 위체류 약물전달시스템에 비해 안정성이 높아 개발목표기술로 선정하였고, 팽윤성 기제로는 기존의 연구와 다르게 카라기난과 히프로멜로오스를 병용하여 차별성을 확보하였다. 카라기난과 히프로멜로오스 병용 시스템은 각각의 함량이 15/110 질량분율일 때 가장 높은 팽윤성과 적절한 서방성 용출패턴을 나타내었다. 또한 각각의 함량이 15 %와 14 %가 되도록 제조한 메트포르민 정제를 시판 정제와 비교 시 더 우수한 팽윤성이 나타남을 확인하였다. 결론적으로 본 연구 결과에 의해 메트포르민의 서방출을 위한 새로운 팽윤성 위체류 약물전달시스템이 개발되었으며 다양한 주성분에 대한 추가적인 연구가 수행되면 의약품, 화장품, 건강기능식품 등의 분야에서 효과적인 약물전달시스템으로 응용될 수 있을 것으로 기대된다.

Keywords

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