다양한 친수성 고분자를 이용한 삼중층 정제의 니페디핀 서방화 및 특성분석

이천중; 하현정; 김수영; 박진영; 장나금; 송정은; 강길선; Cheon Jung Lee; 하현정; Su Young Kim; Jin Young Park; Na Keum Jang; Jeong Eun Song; Gilson Khang

Polymer(Korea), Vol.39, No.5, 739-745, September, 2015

DOI10.7317/pk.2015.39.5.739 Export Citation

다양한 친수성 고분자를 이용한 삼중층 정제의 니페디핀 서방화 및 특성분석

Sustained Release Formulation and Characterization of Nifedipine Three-layered Tablet Using Various Polymers

이천중, 하현정, 김수영, 박진영, 장나금, 송정은 , 강길선 ^†

전북대학교 BIN융합공학과, 고분자나노공학과, 고분자융합소재연구소

Cheon Jung Lee, 하현정, Su Young Kim, Jin Young Park, Na Keum Jang, Jeong Eun Song , and Gilson Khang^†

Dept. of BIN Fusion Technology, Polymer Fusion Research Center & Dept. of PolymerNano Science Technology, Chonbuk National Unviersity, 567 Baekje-daero, Jeonju 561-756, Korea

E-mail:

초록

니페디핀은 고혈압 치료제로 쓰이는 약물로 난용성이기 때문에 용출률의 개선이 필요한 약물이다. 또한 반감기가 1.5~2시간 정도로 짧기 때문에 약물방출을 서방화시킬 필요성이 있다. 본 연구에서는 니페디핀의 약물 방출을 조절하기 위하여 다중층 정제를 통한 24시간 방출제어를 목표로 하였다. 다중층 정제는 윗층과 아래층 그리고 가운데층의 세층으로 이루어지며 윗층과 아래층은 gel-forming 고분자를 이용하여 방출조절을 시도하였다. 가운데 층은 니페디핀의 용출률 향상을 위해 니페디핀과 폴리비닐프롤리돈 K30의 고체분산체를 제조하여 사용하였다. 고체분산체 분석을 위한 SEM, XRD 그리고 DSC분석을 실시하였으며, 인공장액(pH 6.8)에서 생체 외 용출거동을 24시간동안 실시하였다. 실험 결과, 여러 종류의 친수성 고분자 종류 중 하이드록시프로필 메틸셀룰로스 K15M을 사용한 니페디핀 삼중층 제형이 가장 좋은 서방형 패턴과 용출률을 확인할 수 있었다. 이를 통해 니페디핀의 서방화 가능성을 확인할 수 있었다.

Nifedipine is mainly used for treatment of antianginal (especially in Prinzmetal’s angina) and antihypertensive. However, it is needed to improve the dissolution rate because it is poorly water-soluble drug. Nifedipine needs the sustained release formulation due to its short half-life of 1.5~2 h. Therefore, the purpose of this study is to control the burst release of nifedipine through the multi-layer as three layers formulation for 24 h. Upper and bottom layers consisted of gel-forming polymers as release controlling agent, and the middle layer was prepared by nifedipin-PVP K30 solid dispersion. The prepared solid dispersion was analyzed by SEM, XRD and DSC. The prepared multi-layer tablet was characterized by swelling assays. The release behavior of nifedipine from the multi-layer tablet was confirmed through in vitro assay (pH 6.8). It was confirmed that the nifedipine three-layered tablet using hydroxypropylmethyl cellulose (HPMC) K15M showed the best of sustained pattern and dissolution behavior.

Keywords:sustained release;multi-layer formulation;nifedipine;PVP K30;hydroxypropylmethyl cellulose (HPMC)

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[2] Ashraf M, Iuorno VL, Coffin-Beach D, Evans CA, Augsburger LL, Pharm. Res., 11, 733 (1994)

[3] Huang J, Wigent RJ, Bentzley CM, Schwartz JB, Int. J. Pharm., 319, 44 (2006)

[4] Suzuki H, Sunada H, Chem. Pharm. Bull., 45, 1688 (1997)

[5] Yusof WZ, Singapore Medical J., 29, 498 (1988)

[6] Li MHL, Khang G, Gao J, Int. J. Pharm. Sci., 3, 65 (2013)

[7] Tran TT, Tran PH, Lee BJ, Eur. J. Pharm. Sci., 72, 83 (2009)

[8] Ohara T, Kitamura S, Kitagawa T, Terada K, Int. J. Pharm., 302, 95 (2005)

[9] Dave RH, Patel AD, Donahue E, Patel HH, Drug Dev. Ind. Pharm., 38, 930 (2012)

[10] Woo Y, Na K, Int. J. Tissue Regen., 3, 63 (2012)

[11] Mizoe T, Beppu S, Ozeki T, Okada H, J. Contr. Rel., 120, 205 (2007)

[12] Ormes JD, Zhang D, Chen AM, Hou S, Krueger D, Nelson T, Templeton A, Pharm. Dev. Technol., 18, 121 (2013)

[13] Rujivipat S, Bodmeier R, Eur. J. Pharm. Sci., 76, 486 (2010)

[14] Paudel A, Van den Mooter G, Pharm. Res., 29, 251 (2012)

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[17] Mizoe T, Beppu S, Ozeki T, Okada H, J. Contr. Rel., 120, 205 (2007)

[18] Bertrand G, Roy P, Filiatre C, Coddet C, Chem. Eng. Sci., 60(1), 95 (2005)

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[20] Yang DH, Chun HJ, Int. J. Tissue Regen., 4, 41 (2013)

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[23] Lu S, Ramirez WF, Anseth KS, J. Pharm. Sci., 89, 45 (2000)