분무건조 방법으로 제조된 미립구에서 Sibutramine의 방출거동

박정수; 오정수; 오재민; 김윤태; 이준희; 모종현; 이해방; 강길선; Jung Soo Park; Jung Soo Oh; Jae Min Oh; Yun Tae Kim; Jun Hee Lee; Jong Hyun Mo; Hai Bang Lee; Gilson Khang

Polymer(Korea), Vol.32, No.3, 193-198, May, 2008

Export Citation

분무건조 방법으로 제조된 미립구에서 Sibutramine의 방출거동

Sibutramine Release Behavior from Microspheres Prepared by Spray-Dry Method

박정수 , 오정수, 오재민, 김윤태, 이준희, 모종현, 이해방 ¹, 강길선 ^†

전북대학교 BK-21 고분자 BIN 융합 연구팀
¹한국화학연구원 생체분자전달제어팀

Jung Soo Park , Jung Soo Oh, Jae Min Oh, Yun Tae Kim, Jun Hee Lee, Jong Hyun Mo, Hai Bang Lee¹, and Gilson Khang^†

BK-21 Polymer BIN Fusion Research Team, Chonbuk National University, 664-14 Dukjin, Jeonju 561-756, Korea
¹Nanobiomaterials Lab., Korea Research Institute of Chemical Technology, P. O. BOX 107, Yuseong, Daejeon 305-506, Korea

E-mail:

초록

시부트라민은 비만을 치료하기 위한 식욕억제제로서 높은 결정성을 갖는 난용성 약물이다. 이러한 난용성 약물의 용해도를 증가시키기 위하여 고체분산법을 바탕으로 한 분무건조기를 이용하여 미립구를 제조할 수 있었다. 제조된 미립구는 주사전자현미경을 이용하여 제조시 사용한 용매에 따른 미립구 형태차이를 확인할 수 있었으며 용매증발 속도가 빠를수록 구형을 이루는 것을 확인할 수 있었다. X선 회절기를 이용하여 제조된 미립구에서 시부트라민의 결정성이 10%이하로 감소되었음을 확인하였다. 제조된 미립구는 pH 1.2와 pH 6.8에서 방출을 실시하였으며 시부트라민이 pH에 따라서 용해도 차이가 크다는 것을 확인하였다. 또한, 경질 캡슐을 이용한 것이 정제형태보다 방출이 약 4배 정도 빠르다는 것을 확인할 수 있었다. 이러한 결과를 바탕으로 제형의 형태에 따라 방출거동이 조절될 수 있음을 확인하였다.

Sibutramine is a highly crystalline and poorly water soluble drug as the appetite depressant for obesity treatment. In order to increase water solubility of sibutramine, microspheres including sibutramine were prepared by solid dispersion method using a spray dryer. The crystallinity and morphology of the prepared microspheres were confirmed by SEM and XRD. The morphology of microspheres has gradually changed into spherical shape as increasing evaporation rate of solvent. According to XRD analysis, crystallinity of sibutramine in microspheres was decreased by below 10%. Release behavior of microspheres was investiaged at pH 1.2, pH 6.8, and solubility of the sibutramine was significantly different depending on pH. The hard capsule showed fast release of sibutramine comparing with the tablet. These results demonstrated that the pharmaceutical preparation is able to control the release behaviors.

Keywords:sibutramine;microsphere;spray dryer;controlled release

[References]

Kopelman PG, Reply FN, Int. J. Obes. Relat. Metab. Disord., 25, 1405 (2001)
N. Finer, Best Pract. Res. Clin. Endocrinol. Metab., 16, 717 (2002)
Lean MEJ, Medicine, 34, 515 (2006)
Brundtland GH, WHO, Geneva (2002)
Padwal RS, Majumdar SR, Lancet, 369, 71 (2007)
Halford JCG, Appetite, 46, 6 (2006)
Lee J, Teoh T, Lee T, J. Psychosom. Res., in press (2008)
Bray GA, Blackburn GL, Ferguson JM, Greenway FL, Jain AK, Mendel CM, Mendel J, Ryan DH, Schwartz SL, Scheinbaum ML, Seaton TB, Obes Res., 7, 189 (1999)
Luque CA, Rey JA, Pharmacotherapy, 26, 222s (2006)
Park YJ, Son YJ, Korea Patent 10-0008787 (2007)
Jeon HR, Kwon DW, Lee BS, Oh SH, Oh DY, Park JS, Yu SK, Korea Patent 10-0627687 (2006)
bolfathi Z, Couture J, Vallee F, LeBel M, Tanguay M, Masson E, J. Pharm. Pharmaceut Sci., 7, 345 (2004)
Youn JY, Ku J, Lee SY, Kim BS, Kim MS, Lee B, Khang G, Lee HB, Polym.(Korea), 31(4), 329 (2007)
Iwata M, Ueda H, Drug Dev. Int. J. Pharm., 22, 1161 (1996)
Lu WG, Zhang Y, Xiong QM, Bao YC, Chen QH, Chin. Pharm. J., 30, 24 (1995)
Chowdary KP, Ramesh KV, Indian Drugs, 32, 477 (1995)
An TK, Kang HJ, Moon DS, Lee JS, Seong H, Jeong JK, Khang G, Lee HB, Polym.(Korea), 26(5), 670 (2002)
Jang WY, Kim SH, Lee IW, Kim MS, Rhee JM, Khang G, Lee HB, Tissue Eng. Regen. Med., 2, 100 (2005)
Seo KS, Hong KD, Hyun H, Kim MS, Khang G, Lee HB, Tissue Eng. Regen. Med., 2, 109 (2005)
Khang G, Kim MS, Cho SH, Lee I, Rhee JM, Lee HB, Tissue Eng. Regen. Med., 1, 9 (2004)
Kim SK, Hong KD, Kim SH, Kim MS, Khang G, Lee IW, Han CW, Lee HK, Lee HB, Tissue Eng. Regen. Med., 2, 130 (2005)
Cho KJ, Song DK, Oh SH, Koh YJ, Lee SH, Lee MC, Lee JH, Tissue Eng. Regen. Med., 2, 115 (2005)
Lee JS, Shin JH, Jeong JK, Rhee JM, Lee HB, Khang G, Polym.(Korea), 27(1), 9 (2003)
Chung TS, J. Membr. Sci., 126(1), 19 (1997)
Vasir JK, Tambwekar K, Garg S, Int. J. Pharm., 255, 13 (2003)
Masters K, Spray Drying Handbook, 4th ed., George Goodwin, Ltd., London (1985)
Yan C, Resau JH, Hewetson J, J. Control. Release, 32, 231 (1994)
McGee JP, Singh M, Li XM, J. Microencapsul., 14, 197 (1997)
Schlicher EJAM, Postma NS, Zuidema J, Int. J. Pharm., 153, 235 (1997)
Oh J, Jeong JK, Kim J, Cho SH, Khang G, Lee JS, Lee HB, Macromol. Chem. Symp., 15, 4 (2000)

[Referenced By]

[Related Articles]

[1] Kopelman PG, Reply FN, Int. J. Obes. Relat. Metab. Disord., 25, 1405 (2001)

[2] N. Finer, Best Pract. Res. Clin. Endocrinol. Metab., 16, 717 (2002)

[3] Lean MEJ, Medicine, 34, 515 (2006)

[4] Brundtland GH, WHO, Geneva (2002)

[5] Padwal RS, Majumdar SR, Lancet, 369, 71 (2007)

[6] Halford JCG, Appetite, 46, 6 (2006)

[7] Lee J, Teoh T, Lee T, J. Psychosom. Res., in press (2008)

[8] Bray GA, Blackburn GL, Ferguson JM, Greenway FL, Jain AK, Mendel CM, Mendel J, Ryan DH, Schwartz SL, Scheinbaum ML, Seaton TB, Obes Res., 7, 189 (1999)

[9] Luque CA, Rey JA, Pharmacotherapy, 26, 222s (2006)

[10] Park YJ, Son YJ, Korea Patent 10-0008787 (2007)

[11] Jeon HR, Kwon DW, Lee BS, Oh SH, Oh DY, Park JS, Yu SK, Korea Patent 10-0627687 (2006)

[12] bolfathi Z, Couture J, Vallee F, LeBel M, Tanguay M, Masson E, J. Pharm. Pharmaceut Sci., 7, 345 (2004)

[13] Youn JY, Ku J, Lee SY, Kim BS, Kim MS, Lee B, Khang G, Lee HB, Polym.(Korea), 31(4), 329 (2007)

[14] Iwata M, Ueda H, Drug Dev. Int. J. Pharm., 22, 1161 (1996)

[15] Lu WG, Zhang Y, Xiong QM, Bao YC, Chen QH, Chin. Pharm. J., 30, 24 (1995)

[16] Chowdary KP, Ramesh KV, Indian Drugs, 32, 477 (1995)

[17] An TK, Kang HJ, Moon DS, Lee JS, Seong H, Jeong JK, Khang G, Lee HB, Polym.(Korea), 26(5), 670 (2002)

[18] Jang WY, Kim SH, Lee IW, Kim MS, Rhee JM, Khang G, Lee HB, Tissue Eng. Regen. Med., 2, 100 (2005)

[19] Seo KS, Hong KD, Hyun H, Kim MS, Khang G, Lee HB, Tissue Eng. Regen. Med., 2, 109 (2005)

[20] Khang G, Kim MS, Cho SH, Lee I, Rhee JM, Lee HB, Tissue Eng. Regen. Med., 1, 9 (2004)

[21] Kim SK, Hong KD, Kim SH, Kim MS, Khang G, Lee IW, Han CW, Lee HK, Lee HB, Tissue Eng. Regen. Med., 2, 130 (2005)

[22] Cho KJ, Song DK, Oh SH, Koh YJ, Lee SH, Lee MC, Lee JH, Tissue Eng. Regen. Med., 2, 115 (2005)

[23] Lee JS, Shin JH, Jeong JK, Rhee JM, Lee HB, Khang G, Polym.(Korea), 27(1), 9 (2003)

[24] Chung TS, J. Membr. Sci., 126(1), 19 (1997)

[25] Vasir JK, Tambwekar K, Garg S, Int. J. Pharm., 255, 13 (2003)

[26] Masters K, Spray Drying Handbook, 4th ed., George Goodwin, Ltd., London (1985)

[27] Yan C, Resau JH, Hewetson J, J. Control. Release, 32, 231 (1994)

[28] McGee JP, Singh M, Li XM, J. Microencapsul., 14, 197 (1997)

[29] Schlicher EJAM, Postma NS, Zuidema J, Int. J. Pharm., 153, 235 (1997)

[30] Oh J, Jeong JK, Kim J, Cho SH, Khang G, Lee JS, Lee HB, Macromol. Chem. Symp., 15, 4 (2000)