CMC와 HPMC를 이용한 잘토프로펜 정제의 용출률 개선

박현진; 홍희경; 송이슬; 홍민성; 서한솔; 홍동현; 이동원; 강길선; Hyun Jin Park; Hee Kyung Hong; Yi Seul Song; Min Sung Hong; Han Sol Seo; Dong Hyun Hong; Dongwon Lee; Gilson Khang

Polymer(Korea), Vol.34, No.4, 300-305, July, 2010

Export Citation

CMC와 HPMC를 이용한 잘토프로펜 정제의 용출률 개선

Improvement of Dissolution Rate for Zaltoprofen Tablets Using CMC and HPMC

박현진, 홍희경, 송이슬, 홍민성, 서한솔, 홍동현, 이동원 , 강길선 ^†

전북대학교 BIN 융합공학과, 고분자나노공학과

Hyun Jin Park, Hee Kyung Hong, Yi Seul Song, Min Sung Hong, Han Sol Seo, Dong Hyun Hong, Dongwon Lee , and Gilson Khang^†

Department of BIN Fusion Technology & Department of Polymer·Nano Science& Technology, Chonbuk National University, 664-14 Dukjin, Jeonju 561-756, Korea, Korea

E-mail:

초록

잘토프로펜(zaltotprofen)은 통증 치료와 염증 억제에 주로 사용되는 비스테로이드성 약물로, 류머티스 관절염 치료 및 해열 진통에 효능을 나타내는 약물이다. 잘토프로펜은 물에는 거의 녹지 않는 난용성 약물이다. 이러한 난용성을 개선하여 흡수율을 증진시키고 생체이용률이 향상된 제제를 제공하기 위하여 여러 첨가제를 이용하여 타블렛으로 제조하였다. 첨가제로는 락토스, 히드록시프로필메틸셀룰로오스 (HPMC), 카복시메틸셀룰로오스(CMC)를 사용하였고 제조된 약물의 구조와 결정화도의 변화를 FTIR과 DSC를 이용하여 분석하였다. 시판제제인 솔레톤정®과 비교하여 생체외 방출 거동 실험을 하였고 실험결과 전체적으로 초기 약물 방출을 줄일 수 있었고 점차 방출률이 늘어나 시판제제보다 더 높은 약물 방출을 보였다. 저점도의 HPMC는 고점도의 HPMC를 첨가했을 때보다 더 높은 약물 방출을 보였고 CMC의 양이 많아질수록 또한 약물 방출이 높게 나타났다.

Zaltoprofen is a propionic acid derivative of non-steroidal anti-inflammatory drugs (NSAIDs) and has been widely used in the treatment of a number of arthritic conditions or lumbago. Zaltoprofen has low water solubility and low bioavailability, therefore great efforts have been devoted to enhance the extent of drug adsorption. In this study, zaltoprofen was formulated into a tablet to enhance the bioavailability and to achieve sustained-release using additives such as lactose monohydrate, carboxymethylcellulose (CMC), hydroxypropylmethylcellulose (HPMC). Fourier transform-infrared (FTIR) and differential scanning calorimeter (DSC) were employed to study the structure and crystallization of zaltoprofen in the tablet with various contents of additives. It was found that additives had interactions with zaltoprofen and inhibited the crystallization of zaltoprofen. Tablets containing low viscosity HPMC showed a higher release than those containing high viscosity HPMC. Also, as the amount of CMC increased zaltoprofen release increased.

Keywords:zaltoprofen;dissolution rate;bioavailability;HPMC;CMC

[References]

Matsumoto M, Inoue M, Ueda H, Neurosci. Lett., 397, 249 (2006)
Tanga HB, Inouea A, Oshitab K, Hiratec K, Nakataa Y, Neuropharmacology, 48, 1035 (2005)
Hirate K, Uchida A, Ogawa Y, Arai T, Yoda K, Neurosci. Res., 54, 288 (2006)
Kuno Y, Kojima M, Ando S, Nakagami H, J. Control. Release, 105, 16 (2005)
Shah AC, Britten NJ, J. Control. Release, 14, 179 (1990)
Mir VG, Heinamaki J, Antikainen O, Revoredo OB, Colarte AI, Nieto OM, Yliruusi J, Eur. J. Pharm. Biopharm., 69, 964 (2008)
Steendam R, Lerk CF, Int. J. Pharm., 175, 33 (1998)
Kirk JH, Dann SE, Blatchford CG, Int. J. Pharm., 334, 103 (2006)
Harwood LM, Experimental Organic Chemistry, Harwood LM, Moody CJ, Percy JM, Editors, Blackwell Science Ltd., Oxford, p 683 (1999)
Dapier-Beche N, Fanni J, Parmentier M, J. Dairy. Sci., 82, 2558 (1999)
Khan GM, Zhu JB, J. Control. Release, 56, 127 (1998)
Takahashi Y, Takeda C, Seto I, Kawano G, Machida Y, Int. J. Pharm., 343, 220 (2007)
Abdel-Rahman SI, Mahrous MG, El-Badry M, Saudi. Pharm. Journal, 17, 283 (2009)
Bin C, Joshi SC, Lam YC, Carbohydr. Polym., 75, 282 (2009)
Ribeiro L, Ferreira DC, Veiga FJB, J. Control. Release, 103, 325 (2005)
Miyazaki S, Kawasaki N, Nakamura T, Iwatsu M, Hayashi T, Hou WM, Attwood D, Int. J. Pharm., 204, 127 (2000)
Ishikawa T, Watanabe Y, Takayama K, Endo H, Matsumoto M, Int. J. Pharm., 202, 173 (2000)
Zuurman K, Maarschalk KVV, Bolhuis GK, Int. J. Pharm., 179, 107 (1999)
Fukui E, Miyamura N, Kobayashi M, Int. J. Pharm., 216, 137 (2001)
Park JH, Ku J, Ahn SI, Lee JH, Kim YT, Kim DS, Kim W, Rhee JM, Khang G, Tissue Eng. Regen. Med., 5, 729 (2008)
Cui Y, Kim SS, Park ES, J. Kor. Pharm. Sci., 32, 95 (2002)
Guchardi R, Frei M, John E, Kaerger JS, Int. J. Pharm., 348, 10 (2008)
Mehrotra A, Llusa M, Faqih A, Levin M, Muzzio FJ, Int. J. Pharm., 336, 284 (2007)
Mura P, Fauucci MT, Manderioli A, Bramanti G, Ceccarelli L, J. Pharmaceut. Biomed., 18, 151 (1998)
Williams AC, Timmins P, Lu M, Forbes RT, Eur. J. Pharm. Sci., 26, 288 (2005)
Ma H, Andrews GP, Jones DS, Walker GM, Chem. Eng. J., in press (2010)
Ozeki Y, Ando M, Watanabe Y, Danjo K, J. Control. Release, 95, 51 (2004)
Juarez H, Rico G, Villafuert L, Int. J. Pharm., 216, 115 (2001)
Varshosaz J, Dehghan Z, Eur. J. Pharm. Biopharm., 54, 135 (2002)
Fukami J, Yonemochi E, Yoshihashi Y, Terada K, Int. J. Pharm., 310, 101 (2006)

[Referenced By]

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[1] Matsumoto M, Inoue M, Ueda H, Neurosci. Lett., 397, 249 (2006)

[2] Tanga HB, Inouea A, Oshitab K, Hiratec K, Nakataa Y, Neuropharmacology, 48, 1035 (2005)

[3] Hirate K, Uchida A, Ogawa Y, Arai T, Yoda K, Neurosci. Res., 54, 288 (2006)

[4] Kuno Y, Kojima M, Ando S, Nakagami H, J. Control. Release, 105, 16 (2005)

[5] Shah AC, Britten NJ, J. Control. Release, 14, 179 (1990)

[6] Mir VG, Heinamaki J, Antikainen O, Revoredo OB, Colarte AI, Nieto OM, Yliruusi J, Eur. J. Pharm. Biopharm., 69, 964 (2008)

[7] Steendam R, Lerk CF, Int. J. Pharm., 175, 33 (1998)

[8] Kirk JH, Dann SE, Blatchford CG, Int. J. Pharm., 334, 103 (2006)

[9] Harwood LM, Experimental Organic Chemistry, Harwood LM, Moody CJ, Percy JM, Editors, Blackwell Science Ltd., Oxford, p 683 (1999)

[10] Dapier-Beche N, Fanni J, Parmentier M, J. Dairy. Sci., 82, 2558 (1999)

[11] Khan GM, Zhu JB, J. Control. Release, 56, 127 (1998)

[12] Takahashi Y, Takeda C, Seto I, Kawano G, Machida Y, Int. J. Pharm., 343, 220 (2007)

[13] Abdel-Rahman SI, Mahrous MG, El-Badry M, Saudi. Pharm. Journal, 17, 283 (2009)

[14] Bin C, Joshi SC, Lam YC, Carbohydr. Polym., 75, 282 (2009)

[15] Ribeiro L, Ferreira DC, Veiga FJB, J. Control. Release, 103, 325 (2005)

[16] Miyazaki S, Kawasaki N, Nakamura T, Iwatsu M, Hayashi T, Hou WM, Attwood D, Int. J. Pharm., 204, 127 (2000)

[17] Ishikawa T, Watanabe Y, Takayama K, Endo H, Matsumoto M, Int. J. Pharm., 202, 173 (2000)

[18] Zuurman K, Maarschalk KVV, Bolhuis GK, Int. J. Pharm., 179, 107 (1999)

[19] Fukui E, Miyamura N, Kobayashi M, Int. J. Pharm., 216, 137 (2001)

[20] Park JH, Ku J, Ahn SI, Lee JH, Kim YT, Kim DS, Kim W, Rhee JM, Khang G, Tissue Eng. Regen. Med., 5, 729 (2008)

[21] Cui Y, Kim SS, Park ES, J. Kor. Pharm. Sci., 32, 95 (2002)

[22] Guchardi R, Frei M, John E, Kaerger JS, Int. J. Pharm., 348, 10 (2008)

[23] Mehrotra A, Llusa M, Faqih A, Levin M, Muzzio FJ, Int. J. Pharm., 336, 284 (2007)

[24] Mura P, Fauucci MT, Manderioli A, Bramanti G, Ceccarelli L, J. Pharmaceut. Biomed., 18, 151 (1998)

[25] Williams AC, Timmins P, Lu M, Forbes RT, Eur. J. Pharm. Sci., 26, 288 (2005)

[26] Ma H, Andrews GP, Jones DS, Walker GM, Chem. Eng. J., in press (2010)

[27] Ozeki Y, Ando M, Watanabe Y, Danjo K, J. Control. Release, 95, 51 (2004)

[28] Juarez H, Rico G, Villafuert L, Int. J. Pharm., 216, 115 (2001)

[29] Varshosaz J, Dehghan Z, Eur. J. Pharm. Biopharm., 54, 135 (2002)

[30] Fukami J, Yonemochi E, Yoshihashi Y, Terada K, Int. J. Pharm., 310, 101 (2006)