쿠에티아핀 푸마르산을 함유하는 방출제어 캡슐제의 용해특성

김필윤; 정준재; 김남영; 김진우; 최정민; 이원찬; 송정은; 강길선; Pil Yun Kim; Jun Jae Jung; Nam Yeong Kim; Jin Woo Kim; Jeong Min Choi; Won Chan Lee; Jeong Eun Song; Gilson Khang

Polymer(Korea), Vol.44, No.5, 715-724, September, 2020

DOI10.7317/pk.2020.44.5.715 Export Citation

쿠에티아핀 푸마르산을 함유하는 방출제어 캡슐제의 용해특성

Dissolution Properties of Controlled Release Capsules Containing Quetiapine Fumarate

김필윤, 정준재, 김남영, 김진우, 최정민, 이원찬, 송정은 , 강길선 ^†

전북대학교 BIN융합공학과, 고분자나노공학과, 고분자융합소재연구소

Pil Yun Kim, Jun Jae Jung, Nam Yeong Kim, Jin Woo Kim, Jeong Min Choi, Won Chan Lee, Jeong Eun Song , and Gilson Khang^†

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

E-mail:

초록

쿠에티아핀 푸마르산(quetiapine fumarate, QF)은 낮은 용해도와 높은 투과성을 갖는 BCS CLASS Ⅱ로 생체이용률이 낮은 문제가 있다. 또한 쿠에티아핀은 2개의 수산화기를 보유하여, 산성 조건 하에서 더 높은 용해도를 갖는다고 보고되어 있다. 즉, pH 4 이상의 범위에 대해서는 용해도가 낮고, pH 2에서 높은 용해도를 보이며, pH 2 미만에서는 이온 효과로 인하여 용해도가 감소한다. 따라서 QF의 용해도를 향상시키고 pH의 변화에도 일정한 방출을 유도하기 위해 속방 및 서방성 과립물을 이용한 캡슐을 제조하였다. XRD와 DSC를 사용하여 약물의 결정성과 포접을 평가, SEM을 통해 형태학적인 분석, FTIR 분석을 수행하여 화학적 변화를 분석하였다. 또한 습식과립공정을 통해 유동성이 개선된 것을 확인하기 위해 유동성 평가를 하였으며 최종적으로, 용해도 시험으로 고체 분산체 및 캡슐제의 용해도 패턴을 분석하였다.

Quetiapine fumarate (QF) is a BCS CLASS II with low solubility and high permeability, which has a problem of low bioavailability. It has also been reported that Quetiapine possesses two hydroxyl groups, so it has a higher solubility under acidic conditions. The solubility is low in the range of pH 4 or higher and it is high when pH is 2, and it decreases when the pH is lower than 2 which is due to ion effect. Therefore, capsules were prepared using immediate-release and sustained-release granules to improve the solubility of QF and induce constant release even with a change in pH. XRD and DSC were used to evaluate the crystallinity and inclusion of drugs, SEM was used for morphological analysis, and FTIR was used to analyze chemical changes. In addition, fluidity was evaluated to confirm that it was improved by granulation process. Finally, the solubility patterns of solid dispersions and capsules were analyzed by a solubility test.

Keywords:quetiapine fumarate;immediate release;sustained release;controlled release;rotary evaporation;spray dry solid dispersion

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[Related Articles]

[1] Green B, Curr. Med. Res. Opin., 15, 145 (1999)

[2] Gefvert O, Bergstrom M, Langstrom B, Lundberg T, Lindstrom L, Yates R, Psychopharmacology, 135, 119 (1998)

[3] Mundo E, Cattaneo E, Zanoni S, Altamura AC, Neuropsychiatr. Dis. Treat., 2, 139 (2006)

[4] DeVane CL, Nemeroff CB, Clin. Pharmacokinet., 40, 509 (2001)

[5] Talele SG, Derle DV, Int. J. Appl. Pharm., 10, 127 (2018)

[6] Dressman J, Reppas C, Adv. Drug Deliv. Rev., 59, 531 (2007)

[7] Chen H, Khemtong C, Yang X, Chang X, Gao J, Drug Discov. Today, 16, 354 (2011)

[8] Nokhodchi A, Raja S, Patel P, Asare-Addo K, J. Pharm., 2, 175 (2016)

[9] Mehta S, Joseph NM, Feleke F, Palani S, J. Drug Deliv. Ther., 4, 7 (2014)

[10] Re MI, Dry. Technol., 24, 433 (2006)

[11] Gubbala LP, Arutla S, Venkateshwariu V, Int. J. Drug Deliv. Technol., 8, 37 (2016)

[12] Narala A, Veerabrahma K, J. Pharm., 2013, 265741 (2013)

[13] Aulton ME, Editor, Pharmaceutics: The Science of Dosage Form Design, Churchill Livingstone, Edinburgh, 2001.

[14] Chowhan ZT, Amaro AA, Chow YP, Drug Dev. Ind. Pharm., 8, 145 (1982)

[15] Chitu TM, Oulahna D, Hemati M, Powder Technol., 208(2), 441 (2011)

[16] Park JH, Choi HK, Arch. Pharm. Res., 38, 1336 (2015)

[17] Timmins P, Delargy AM, Howard JR, Pharm. Dev. Technol., 2, 25 (1997)

[18] Sung KC, Nixon PR, Skoug JW, Ju TR, Gao P, Topp EM, Patel MV, Int. J. Pharm., 142, 53 (1996)

[19] Pham AT, Lee PI, Pharm. Res., 11, 1379 (1994)

[20] Skoug JW, Mikelsons MV, Vigneron CN, Stemm NL, J. Control. Release, 27, 227 (1993)

[21] Sekikawa H, Nakano M, Arita T, Chem. Pharm. Bull., 26, 118 (1978)

[22] Yagi N, Terashima Y, Kenmotsu H, Sekikawa H, Takada M, Chem. Pharm. Bul., 44, 241 (1996)

[23] Hausner HH, Int. J. Powder Metall., 3, 7 (1967)

[24] Carr RL, Chem. Eng., 18, 163 (1965)

[25] Park H, Baek JS, Kim D, Lee GW, Jeon HY, Song JE, Lee SY, Khang GS, Polym. Korea, 42(2), 275 (2018)

[26] Yang J, Grey K, Doney J, Int. J. Pharm., 384, 24 (2010)

[27] Lifshitz-Liron R, Kovalevski-Ishai E, Dolitzky BZ, Wizel S, Lidor-Hadas R, U.S. Patent Application No. 10/393,929 (2003).