습식과립을 이용한 시나칼세트염산염의 방출거동

이지은; 빈수영; 최정민; 조훈휘; 김남영; 송정은; 강길선; Ji Eun Lee; Suyoung Been; Jeongmin Choi; Hunhwi Cho; Namyeong Kim; Jeong Eun Song; Gilson Khang

Polymer(Korea), Vol.45, No.1, 16-21, January, 2021

DOI10.7317/pk.2021.45.1.16 Export Citation

습식과립을 이용한 시나칼세트염산염의 방출거동

Release Behavior of Cinacalcet Hydrochloride Using Wet Granulation

이지은, 빈수영, 최정민, 조훈휘, 김남영, 송정은 , 강길선 ^†

전북대학교 바이오나노융합공학과, 고분자나노공학과, 고분자융합소재연구소

Ji Eun Lee, Suyoung Been, Jeongmin Choi, Hunhwi Cho, Namyeong Kim, Jeong Eun Song , and Gilson Khang^†

Department of Bionanotechnology and Bio-Convergence Engineering, Department of Polymer Nano Science & Technology and Polymer Materials Fusion Research Center, Jeonbuk National University, 567 Baekje-daero, Jeonju 54896, Korea

E-mail:

초록

만성신부전환자의 이차성 부갑상선 기능 항진 치료제로 알려진 시나칼세트염산염은 BCS class Ⅳ의 특성을 갖는 난용성 약물이다. 난용성 개선을 위하여, 본 연구에서는 수용성 고분자와 난용성 약물 시나칼세트염산염으로 습식과립물을 제조한 후, 첨가제를 비율별로 혼합하여 정제를 설계하였다. FTIR을 이용하여 습식과립 공정에서 일어나는 화학적 변화를 평가하였고, 정상적으로 과립이 형성되었는지 확인하기 위하여 DSC와 XRD를 진행하였다. 이 후 정제가 제대로 설계되었는지 확인하기 위하여 인공위액(pH1.2)에서 방출 실험을 진행하였으며 HPLC를 통하여 측정하였다. 결과적으로 수용성 고분자를 이용한 습식과립물의 제조가 난용성 약물인 시나칼세트염산염의 방출에 효과적인 것을 확인할 수 있었다.

Cinacalcet hydrochloride, known as a treatment for a secondary hyperparathyroidism in a chronic renal failure, is a poorly soluble drug with the properties of BCS class IV. To improve poor solubility, in this study, after preparing a wet granule of soluble polymer and poorly soluble drug cinacalcet hydrochloride, tablets were designed by mixing additives by proportion. Chemical changes occurring in the wet granulation process were evaluated using FTIR, and DSC and XRD were performed to confirm that the granules were formed as designed. After this, the release was tested through HPLC in an artificial gastric acid (pH1.2) to confirm that the tablet was properly designed. As a result, it was confirmed that the formation of the wet granules using a soluble polymer was effective for the release of cinacalcet hydrochloride, a poorly soluble drug.

Keywords:cinacalcet hydrochloride;wet granules;dissolution rate;soluble polymer;poloxamer

[References]

Kim H, So YR, Lee JH, Yun HA, Seok HY, Son JI, et al., The Chonbuk University Medical Journal, 36, 23 2012.
Kim SH, Seo DH, Hwang SD, Kim JW, Int. J. Thyroidol., 12, 54 (2019)
Lee JH, Korean J. Pediatr, 52, 1061 (2009)
Lim VS, Am. J. Kidney Dis., 38, S80 (2001)
Seo HN, Korean J. Clin. Pharm., 23, 142 (2013)
Peacock M, Bilezikian JP, Klassen PS, Guo MD, Turner SA, J. Clin. Endocrinol. Metab., 90, 135 (2005)
Balfour JAB, Scott LJ, Drugs, 65, 271 (2005)
Zitt E, Rix M, Torres UP, Fouque D, Jacobson SH, Petavy F, Ryba M, Dehmel B, Ryda M, Nephrol. Dial. Transplant., 26, 1956 (2011)
Ahn YS, Lee HY, Hong KD, Jung SB, Cho SH, Rhee JM, Lee HB, Khang GS, J. Pharm. Investig., 34, 289 (2004)
Kim HE, Hwang JS, Cho SH, Kim YJ, Huh KM, Polym. Korea, 36, 41 (2011)
Jeon DY, Jang JE, Lee JH, Yang JW, Park SM, Lim D, Khang G, Polym. Korea, 38(4), 434 (2014)
Xu X, Chen G, Li Y, Wang J, Yin J, Ren L, Nanotechnology, 30, 055102 (2018)
Kim YT, Park HJ, Lee YH, Hong HK, Eom S, Kim YK, Lee EY, Choi MG, Lee JJ, Cho YB, Khang G, Polym. Korea, 33(6), 596 (2009)
Lee JH, Kim DS, Kim W, Park JH, Ahn SI, Kim YT, Rhee JM, Khang GS, J. Pharm. Invest., 38, 249 (2008)
Baek JS, Kim JS, Kim WK, Kim D, Song JE, Khang GS, Polym. Korea, 43(3), 410 (2019)
Oh YA, Kim SH, Lee SJ, Yoo JJ, van Dyke M, Rhee JM, Khang G, Polym. Korea, 32(5), 403 (2008)
Yun HY, Baek MS, Kwon KI, Kor. J. Clin. Pharm., 16, 147 (2006)
Hebeish A, Aly AA, El-Shafei A, Zaghloul S, Egypt. J. Chem., 52, 73 (2009)
Yacoubian TA, Neurodegener. Dis. Manag., 3, 123 (2013)
Jeon DY, Jang JE, Lee JH, Yang JW, Park SM, Lim D, Khang G, Polym. Korea, 38(4), 434 (2014)
Shibata M, Otsubo K, Ohara M, Omae R, Niwa T, Danjo K, Yakugaku Zasshi, 132, 1317 (2012)
Park JH, Kim SH, Ahn SI, Choi JH, Lee JH, Kim YT, et al.,, Tissue Eng. Reg. Med., 6, 77 (2009)

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[1] Kim H, So YR, Lee JH, Yun HA, Seok HY, Son JI, et al., The Chonbuk University Medical Journal, 36, 23 2012.

[2] Kim SH, Seo DH, Hwang SD, Kim JW, Int. J. Thyroidol., 12, 54 (2019)

[3] Lee JH, Korean J. Pediatr, 52, 1061 (2009)

[4] Lim VS, Am. J. Kidney Dis., 38, S80 (2001)

[5] Seo HN, Korean J. Clin. Pharm., 23, 142 (2013)

[6] Peacock M, Bilezikian JP, Klassen PS, Guo MD, Turner SA, J. Clin. Endocrinol. Metab., 90, 135 (2005)

[7] Balfour JAB, Scott LJ, Drugs, 65, 271 (2005)

[8] Zitt E, Rix M, Torres UP, Fouque D, Jacobson SH, Petavy F, Ryba M, Dehmel B, Ryda M, Nephrol. Dial. Transplant., 26, 1956 (2011)

[9] Ahn YS, Lee HY, Hong KD, Jung SB, Cho SH, Rhee JM, Lee HB, Khang GS, J. Pharm. Investig., 34, 289 (2004)

[10] Kim HE, Hwang JS, Cho SH, Kim YJ, Huh KM, Polym. Korea, 36, 41 (2011)

[11] Jeon DY, Jang JE, Lee JH, Yang JW, Park SM, Lim D, Khang G, Polym. Korea, 38(4), 434 (2014)

[12] Xu X, Chen G, Li Y, Wang J, Yin J, Ren L, Nanotechnology, 30, 055102 (2018)

[13] Kim YT, Park HJ, Lee YH, Hong HK, Eom S, Kim YK, Lee EY, Choi MG, Lee JJ, Cho YB, Khang G, Polym. Korea, 33(6), 596 (2009)

[14] Lee JH, Kim DS, Kim W, Park JH, Ahn SI, Kim YT, Rhee JM, Khang GS, J. Pharm. Invest., 38, 249 (2008)

[15] Baek JS, Kim JS, Kim WK, Kim D, Song JE, Khang GS, Polym. Korea, 43(3), 410 (2019)

[16] Oh YA, Kim SH, Lee SJ, Yoo JJ, van Dyke M, Rhee JM, Khang G, Polym. Korea, 32(5), 403 (2008)

[17] Yun HY, Baek MS, Kwon KI, Kor. J. Clin. Pharm., 16, 147 (2006)

[18] Hebeish A, Aly AA, El-Shafei A, Zaghloul S, Egypt. J. Chem., 52, 73 (2009)

[19] Yacoubian TA, Neurodegener. Dis. Manag., 3, 123 (2013)

[20] Jeon DY, Jang JE, Lee JH, Yang JW, Park SM, Lim D, Khang G, Polym. Korea, 38(4), 434 (2014)

[21] Shibata M, Otsubo K, Ohara M, Omae R, Niwa T, Danjo K, Yakugaku Zasshi, 132, 1317 (2012)

[22] Park JH, Kim SH, Ahn SI, Choi JH, Lee JH, Kim YT, et al.,, Tissue Eng. Reg. Med., 6, 77 (2009)