PVP 첨가에 의해 제조된 올메사탄 메독소밀 고체분산체의 방출패턴 연구

오승창; 이천중; 이현구; 박진영; 정현기; 김영래; 임동권; 이동원; 강길선; Seung-Chang Oh; Cheon Jung Lee; Hyun Gu Lee; Jin Young Park; Hyun Ki Jeong; Young-Lae Kim; Dong-Kwon Lim; Dongwon Lee; Gilson Khang

Polymer(Korea), Vol.39, No.1, 33-39, January, 2015

Export Citation

PVP 첨가에 의해 제조된 올메사탄 메독소밀 고체분산체의 방출패턴 연구

Release Behavior of Olmesartan Medoxomil from Solid Dispersion Prepared by PVP Addition

오승창, 이천중, 이현구, 박진영, 정현기, 김영래, 임동권, 이동원 , 강길선 ^†

전북대학교 BIN융합공학과, 고분자나노공학과, 고분자융합소재연구소

Seung-Chang Oh, Cheon Jung Lee, Hyun Gu Lee, Jin Young Park, Hyun Ki Jeong, Young-Lae Kim, Dong-Kwon Lim, Dongwon Lee , and Gilson Khang^†

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

E-mail:

초록

올메사탄은 BCS 2단계에 해당하는 약물로 물에 잘 녹지 않는 난용성 약물이다. 이런 약물이 낮은 생체이용률과 제형을 설계하는 과정에서 어려움을 주는 원인이 된다. 본 연구에서는 올메사탄을 분무건조법 및 회전용매증발법을 이용해 고체분산체를 제조하여 제법에 따른 난용성약물의 용출률을 확인하였다. 수용성 고분자로 PVP를 사용하여 약물과 고분자의 비율별로 고체분산체를 제조하였다. SEM을 이용하여 고체분산체의 형태학적인 특성을 분석하였고, 고체분산체의 결정학적 성질은 XRD와 DSC를 통하여 확인하였다. 또한 FTIR을 통해 화학적인 변화를 확인하고, 생체 외 용출거동 실험을 통하여 변화된 용출률을 확인하였다. 제조된 고체분산체는 pH 1.2에서 용출을 확인하였으며, 올메텍과 용출률을 비교하였으며, 분무건조를 통해 약물의 용출률을 향상시킬 수 있다는 것을 확인할 수 있다.

Olmesartan affiliated to biopharmaceutics classification system class 2 is a poorly water soluble drug. For this reason, olmesartan showed a low bioavailability and a lot of difficulties in the process of designing the pharmaceutical formulation. We prepared the solid dispersions of olmesartan. We confirmed the dissolution rate of drug which was prepared by manufacturing. The pharmaceutical formulation of solid dispersions was designed by using PVP as water soluble polymer. We analyzed morphological feature of solid dispersion by employing a scanning electron microscope. Then, the crystalline property of solid dispersion was confirmed through X-ray diffraction and differential scanning calorimeter. Also, the chemical change of solid dispersion was confirmed by the Fourier transform infrared spectroscopy. In vitro dissolution test was used to analyze the dissolution rate of solid dispersion. The prepared solid dissolution olmesartan confirmed the dissolution rate in the pH 1.2. It was compared with olmetec and improved dissolution rate through solid dispersion.

Keywords:olmesartan;spray-dry;solid dispersion;rotary evaporation;PVP K30.

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[1] Nagata R, Kawabe K, Ikeda K, J. Stroke Cerebrovasc. Dis., 19, 236 (2010)

[2] Lorenzen JM, Neunhoffer H, David S, Kielstein JT, Haller H, Fliser D, Atherosclerosis, 209, 184 (2010)

[3] Sakairi A, Ishida J, Honjo K, Inaba S, Nakamura S, Sugiyama F, Yagami K, Fukamizu A, Hypertens. Res., 31, 2165 (2008)

[4] Sukumaran V, Veeraveedu PT, Lakshmanan AP, Gurusamy N, Yamaguchi K, Ma M, Suzuki K, Kodama M, Watanabe K, Free Radic. Res., 46, 850 (2012)

[5] Graham DJ, Ding X, Saneinejad S, Zhou EH, Calia K, Levenson M, Gelperin K, Rose M, Hammad TA, MaCurdy TE, Worrall C, Kelman JA, Pharmacoepidem. Dr. S., 21, 162 (2012)

[6] Ohki R, Yamamoto K, Ueno S, Mano H, Ikeda U, Shimada K, Cardiovasc. Drug Ther., 17, 231 (2003)

[7] Miyashita Y, Saiki A, Endo K, Ban N, Yamaguchi T, Kawana H, Nagayama D, Ohira M, Oyama T, Shirai K, J. Atheroscler. Thromb., 16, 621 (2009)

[8] Ichikawa S, Takayama Y, Russ. J. Cardiol., 3, 33 (2011)

[9] Tsutamoto T, Nishiyama K, Yamaji M, Kawahara C, Fujii M, Yamamoto T, Horie M, Hypertens. Res., 33, 118 (2010)

[10] Tambe SR, Shinde RH, Gupta LR, Pareek V, Bhalerao SB, J. Liq. Chromatogr. R. T., 33, 423 (2010)

[11] Chandra A, Agrawal RC, Mahipal YK, J. Phys. D: Appl. Phys., 42 (2009)

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

[13] Shah J, Vasanti S, Anroop B, Vyas H, J. Incl. Phenom. Macrocycl. Chem., 63, 69 (2009)

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

[15] Gupta P, Kakumanu VK, Bansal AK, Pharm. Res., 21, 1762 (2004)

[16] Thybo P, Kristensen J, Hovgaard L, Pharm. Dev. Technol., 12, 43 (2007)

[17] Weuts I, Kempen D, Decorte A, Verreck G, Peeters J, Brewster M, Van den Mooter G, Eur. J. Pharm. Sci., 25, 313 (2005)

[18] Barmpalexis P, Koutsidis I, Karavas E, Louka D, Papadimitriou SA, Bikiaris DN, Eur. J. Pharm. Biopharm., 85, 1219 (2013)

[19] Haberl N, Hirn S, Wenk A, Diendorf J, Epple M, Johnston BD, Krombach F, Kreyling WG, Schleh C, Beilstein J. Nanotechnol., 4, 933 (2013)

[20] Sharma A, Jain CP, Res. Pharm. Sci., 5, 49 (2010)

[21] van Drooge DJ, Hinrichs WL, Visser MR, Frijlink HW, Int. J. Pharmaceut., 310, 220 (2006)

[22] Pokharkar VB, Mandpe LP, Padamwar MN, Ambike AA, Mahadik KR, Paradkar A, Powder Technol., 167(1), 20 (2006)

[23] Gao P, Mol. Pharmaceut., 5, 903 (2008)

[24] Rodier E, Lochard H, Sauceau M, Letourneau JJ, Freiss B, Fages J, Eur. J. Pharm. Sci., 26, 184 (2005)

[25] Chun HJ, Chae GT, Inter. J. Tissue Regen., 3, 1 (2012)

[26] Shinde VR, Pore YV, Rao JV, Lat. Am. J. Pharm., 30, 2011 (2011)

[27] Deshmukh KR, Jain SK, Indian J. Pharm. Educ. Res., 46, 97 (2012)

[28] Park HN, Lee JB, Kwon IK, Inter. J. Tissue Regen., 1, 10 (2010)

[29] Iwata M, Nakamura Y, McGinity JW, J. Microencapsul., 16(1), 49 (1999)

[30] Khang G, Rhee JM, Jeong JK, Lee JS, Kim MS, Cho SH, Lee HB, Macromol. Res., 11(4), 207 (2003)

[31] de Souza JRR, Feitosa JPA, Ricardo NMPS, Trevisan MTS, de Paula HCB, Ulrich CM, Owen RW, Food Hydrocolloid, 33, 10 (2013)

[32] Li C, Li CX, Le YA, Chen JF, Int. J. Pharmaceut., 404, 257 (2011)

[33] Boghra RJ, Kothawade PC, Belgamwar VS, Nerkar PP, Tekade AR, Surana SJ, Chem. Pharm. Bull., 59, 438 (2011)