분무 건조 방식으로 제조한 에프로살탄 고체분산체 제조 및 특성 분석

황준석; 김소희; 조선행; 허강무; Jun Seok Hwang; So Hee Kim; Sun Hang Cho; Kang Moo Huh

Polymer(Korea), Vol.37, No.4, 442-448, July, 2013

Export Citation

분무 건조 방식으로 제조한 에프로살탄 고체분산체 제조 및 특성 분석

Preparation and Characterization of Solid Dispersions of Eprosartan Using Spray Drying Method

황준석, 김소희, 조선행 ¹, 허강무 ^†

충남대학교 고분자공학과
¹한국화학연구원 의약화학연구센터

Jun Seok Hwang, So Hee Kim, Sun Hang Cho¹, and Kang Moo Huh^†

Department of Polymer Science and Engineering, Chungnam National University, Daejeon 305-764, Korea
¹Research Center for Medicinal Chemistry, Division of Drug Discovery Research, Korea Research Institute of Chemical Techonology, 141 Gajeong-ro, Yuseong-gu, Daejeon 305-600, Korea

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초록

본 연구에서는 분무건조방법을 이용하여 고혈압 치료제로 사용되고 있는 난용성 약물인 에프로살탄의 고체분산체 제형을 다양한 조성 하에서 제조 및 평가하고, 효과적인 약물의 용해도 향상을 위한 제조 조건을 최적화하였다. 친수성 고분자 기제로 hydroxylpropylcellulose(HPC)와 poly(vinyl pyrrolidone)(PVP)를 사용하였고, 고분자 계면활성제로 poloxamer 407을 첨가하여 약물과 고분자의 다양한 조성비를 갖는 고체분산체를 제조한 후, 물리화학적 특성을 비교 평가하였다. 친수성 고분자의 조성비 증가와 함께 약물 결정성이 감소되었으며, HPC보다는 PVP가 약물과의 우수한 상용성을 바탕으로 결정화도 감소와 용출거동 개선 효과가 상대적으로 우수하였다. 친수성 고분자로 PVP를 사용한 경우 약물의 결정성이 대부분 사라져 고체분산체 내 대부분의 약물 분자들이 무정형으로 분산되어 있으며 약물의 용출률이 에프로살탄 대비 3~7배 이상 향상되었다.

In this study, we developed and optimized hydrophilic polymer-based solid dispersion formulations (SDs) using a spray drying method for improving the aqueous solubility of eprosartan, one of poorly soluble drugs that has been broadly used for the treatment of high blood pressure. Hydroxylpropylcellulose (HPC) and poly(vinyl pyrrolidone) (PVP) were used as hydrophilic polymer matrices and poloxamer 407 (P407) added as a polymeric surfactant. Various kinds of solid dispersions with different drug/polymer compositions were prepared and their physico-chemical properties were compared. As the polymer content increased, the drug crystallinity in the SDs significantly decreased and the dissolution properties were enhanced. The PVP based SDs were observed to have relatively reduced crystallinity and an enhanced dissolution rate than HPC-based SDs, due to better miscibility between drug and polymer matrix. For PVP based SDs, the drug crystallinity almost disappeared and the dissolution properties significantly increased by more than 3~7 times.

Keywords:eprosartan;solid dispersion;spray drying method;hydroxylpropylcellulose;poly(vinyl pyrrolidone);solubility.

[References]

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Shusterman NH, Am. Heart J., 138, 238 (1999)
Gradman AH, Gray J, Maggiacomo F, Punzi H, White WB, Clincal Ther., 21, 442 (1999)
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[2] Sugarwara M, Kadomura S, He X, Eur. J. Pharm. Sci., 26, 1 (2005)

[3] Wong JW, Yuen KH, Int. J. Pharm., 227, 177 (2001)

[4] Vippagunta SR, Maul KA, Tallavajhala S, Int. J. Pharm., 236, 111 (2002)

[5] Martinez M, Amidon G, Clarke L, Jones WW, Mitra A, Riviere J, Adv. Drug Deliv. Rev., 54, 825 (2002)

[6] Vasanthavada M, Tong WQ, Joshi Y, Pharm. Res., 21, 1598 (2004)

[7] Vippagunta SR, Zeren W, Hornung S, J. Pharm. Sci., 96, 294 (2007)

[8] Lin SL, Menig J, J. Pharm. Sci., 57, 2143 (1968)

[9] Ford JL, Pharm. Acta Helvetiae., 61, 69 (1986)

[10] Leuner C, Dressman J, Eur. J. Pharm. Biopharm., 50, 47 (2000)

[11] Lee EY, Oh MJ, Kim SH, Seong KY, Lee YH, Kim SJ, She HS, Lee D, Khang G, Polym.(Korea), 35(2), 113 (2011)

[12] Khang G, Jeong JK, Rhee JM, Jee JS, Lee HB, Macromol. Chem. Symp., 14, 123 (2001)

[13] Aceves JM, Cruz R, Hernandez E, Int. J. Pharm., 195, 45 (2000)

[14] Omelczuk MO, Wang CC, Pope DG, Eur. J. Pharm.Biopharm., 148, 123 (1997)

[15] Billon A, Bataille B, Cassanas G, Jacob M, Int. J. Pharm., 203, 159 (2000)

[16] Zerrouk N, Chemtob C, Arnaud P, Toscani S, Int. J.Pharm., 225, 46 (2001)

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[23] Goldberg A, Gibaldi M, Kanig J, Mayersohn M, J. Pharm.Sci., 55, 581 (1966)

[24] Vilhelmsen T, Eliasen H, Schæfer T, J. Pharm. Sci., 303, 132 (2005)

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