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Received November 8, 2004
Accepted December 10, 2004
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Hydroxypropyl-β-cyclodextrin 포접복합체 제조를 위한 초임계유체 공정 연구
Study of a Supercritical Fluid Process for the Preparation of Hydroxypropyl-β-cyclodextrin Inclusion Complexes
연세대학교 공과대학 화학공학과, 120-749 서울시 서대문구 신촌동 134 1수원대학교 공과대학 화공생명공학과, 445-743 경기도 화성시 봉담읍 와우리 산 2-2
Department of Chemical Engineering, Yonsei University, 134, Sinchon-dong, Seodaemun-gu, Seoul 120-749, Korea 1Department of Chemical and Biochemical Engineering, The University of Suwon, San 2-2, Wau-ri, Bongdam-up, Hwaseong, Gyeonggi 445-743, Korea
gblim@suwon.ac.kr
Korean Chemical Engineering Research, February 2005, 43(1), 110-117(8), NONE Epub 4 March 2005
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Abstract
초임계유체를 이용한 공정을 통하여 물에 대해 난용성 성질을 지니는 약물인 itraconazole과 2-hydroxypropyl-β-cyclodextrin(HP-β-CD)의 포접복합체를 제조하였다. 제조된 포접복합체는 SEM, DSC, XRD 등을 이용하여 고체상태의 특성 분석을 수행하여 itraconazole의 결정성적 특성이 HP-β-CD와의 포접체를 형성하며 무정질적으로 변화된 것을 확인할 수 있었다. pH 1.2의 인공위액을 이용하여 수행된 수용액 내에서의 포접복합체의 용해도 및 용출시험 결과 itraconazole 원재료에 비하여 20-200배 정도의 증가된 용해도 결과를 얻을 수 있었다. 초임계유체 공정을 통하여 얻어진 포접복합체의 용해도는 압력증가에 의한 이산화탄소 밀도 증가에 따라 증가하였으며 동일 조건에서 용액 중의 HP-β-CD의 함량에 높아질수록 증가하였다. 35 ℃, 140 bar의 공정 조건에서 itraconazole과 HP-β-CD의 구성 몰비가 1:3인 용액을 사용하였을 경우 itraconazole 원재료에 비하여 약 200배 이상의 용해도인 758.6 μg/mL의 용해도를 지니는 포접복합체를 얻을 수 있었다. 용출시험 결과 투입 약물의 90% 이상이 용출 개시 5-10분 내에 용출되어 대조제로 사용한 시판제제 및 원재료에 비하여 매우 빠른 초기 방출률과 우수한 용출 특성을 확인할 수 있었다. 본 연구를 통하여 기존의 시간소비성 및 다단계의 포접체 제조공정을 개선할 수 있는 한 방법으로 초임계유체 공정이 적용될 가능성을 확인할 수 있었다.
In this work, solid-state inclusion complex powders of itraconazole and 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) were produced by a supercritical anti-solvent (SAS) process. In order to evaluate the degree of complexation, the thermal behavior of the microparticulate complexes was investigated using differential scanning calorimetry. The experimental results obtained for the solubility and dissolution rate of the microparticulate inclusion complexes in a buffer solution of pH 1.2 showed that the complexation of itraconazole with HP-β-CD results in a significant increase in the solubility and dissolution rate of itraconazole. The particle size of the SAS-produced inclusion complexes was dramatically reduced (<0.1-0.5 μm) compared with untreated itraconazole (30-50 μm) and HP-β-CD (50-100 μm). The solubility of itraconazole was increased with the increase of pressure at a constant temperature to ca. 758.6 μg/mL in an aqueous medium of pH 1.2. The dissolution rate of itraconazole was observed to be significantly improved and about 90% of itraconazole was found to be dissolved within 5-10 min.
References
Thompson DO, Crit. Rev. Ther. Drug Carr. Syst., 14(1), 1 (1997)
Loftsson T, Brewster ME, J. Pharm. Sci., 85, 1017 (1996)
Uekama K, Otagiri M, CRC Crit. Rev. Ther. Drug Carrier Syst., 3, 1 (1987)
MartinDelVallw EM, Process Biochem., 39, 1033 (2004)
Sheehan DJ, Hitchcock CA, Sibley CM, Clin. Microbiol. Rev, 12, 40 (1999)
Warnock DW, J. Antimicrob. Chemoter., 24, 275 (1989)
VanPeer A, Woestenborghs R, Heykants J, Gasparini R, Gauwenbergh G, Eur. J. Clin. Pharmacol., 36, 423 (1989)
Baert LEC, Verreck G, Thone D, "Antifungal Conpositions with Improved Bioavalability", U.S. Patent No. 6,509,038 B2 (2003)
Baert LEC, Verreck G, Thone D, "Solid Mixtures of Cyclodextrin Prepared via Melt-Extrusion", U.S. Patent No. 6,365,188 B1 (2002)
Joseph AB, Bruce LM, Joseph G, Alan EH, John LC, Robert HB, Lois J, Antimicrob. Agents Chemother., 42, 1862 (1998)
Barone JA, Koh JG, Bierman RH, Colaizzi JL, Swanson KA, Gaffar MC, Moskovitz BL, Mechlinski W, VandeVelde V, Antimicrob. Agents Chemother., 37, 778 (1993)
Grant SM, Clissole SP, Drugs, 37, 310 (1989)
Ghorab MK, Adeyeye C, J. Pharm. Sci., 92, 1690 (2003)
Loftsson T, Brewster ME, J. Pharm. Sci., 85, 1017 (1996)
Uekama K, Otagiri M, CRC Crit. Rev. Ther. Drug Carrier Syst., 3, 1 (1987)
MartinDelVallw EM, Process Biochem., 39, 1033 (2004)
Sheehan DJ, Hitchcock CA, Sibley CM, Clin. Microbiol. Rev, 12, 40 (1999)
Warnock DW, J. Antimicrob. Chemoter., 24, 275 (1989)
VanPeer A, Woestenborghs R, Heykants J, Gasparini R, Gauwenbergh G, Eur. J. Clin. Pharmacol., 36, 423 (1989)
Baert LEC, Verreck G, Thone D, "Antifungal Conpositions with Improved Bioavalability", U.S. Patent No. 6,509,038 B2 (2003)
Baert LEC, Verreck G, Thone D, "Solid Mixtures of Cyclodextrin Prepared via Melt-Extrusion", U.S. Patent No. 6,365,188 B1 (2002)
Joseph AB, Bruce LM, Joseph G, Alan EH, John LC, Robert HB, Lois J, Antimicrob. Agents Chemother., 42, 1862 (1998)
Barone JA, Koh JG, Bierman RH, Colaizzi JL, Swanson KA, Gaffar MC, Moskovitz BL, Mechlinski W, VandeVelde V, Antimicrob. Agents Chemother., 37, 778 (1993)
Grant SM, Clissole SP, Drugs, 37, 310 (1989)
Ghorab MK, Adeyeye C, J. Pharm. Sci., 92, 1690 (2003)
