친수성 Poly(ethylene glycol)을 이용한 프란루카스트 고체분산체의 제조 및 특성 분석

김형은; 황준석; 조선행; 김영진; 허강무; Hyeong Eun Kim; Jun Seok Hwang; Sun Hang Cho; Young Jin Kim; Kang Moo Huh

Polymer(Korea), Vol.36, No.1, 41-46, January, 2012

Export Citation

친수성 Poly(ethylene glycol)을 이용한 프란루카스트 고체분산체의 제조 및 특성 분석

Preparation and Characterization of Poly(ethylene glycol) Based Pranlukast Solid Dispersion

김형은, 황준석, 조선행 ¹, 김영진 ^†, 허강무 ^†

충남대학교 고분자공학과
¹한국화학연구원 바이오소재연구센터

Hyeong Eun Kim, Jun Seok Hwang, Sun Hang Cho¹, Young Jin Kim^†, and Kang Moo Huh^†

Department of Polymer Science and Engineering, Chungnam National University, Daejeon 305-764, Korea
¹Nanobiomaterials Laboratories, Korea Research Institute of Chemical Technology, P.O. Box 107, Yusung, Daejeon 305-600, Korea

E-mail:,

초록

본 연구에서는 대표적인 난용성 약물이며, 경구용 천식 치료제 중 하나인 pranlukast의 용해도 및 용출성 개선 제제 개발을 위해 친수성 고분자인 poly(ethylene glycol) (PEG)와 고분자 계면활성제인 poloxamer를 사용하여 열용융법(HM)과 용매증발법(SE)에 의한 고체분산체를 제조하였다. 고체분산체 내 약물의 결정성 변화를 DSC, PXRD로 분석한 결과, 약물의 결정성이 크게 감소하였고, 부분적으로 무정형으로 변화하였음을 확인하였다. 용출시험 및 용해도 분석결과, 고유 약물에 비해 용해도와 용출 속도가 크게 증가하였다. Pranlukast, PEG, poloxamer가 1:5:1의 조성으로 열용융법에 의해 제조된 고체분산체가 가장 우수한 용해도 및 용출속도 향상 결과를 보였다. 결과적으로 PEG과 poloxamer를 이용한 고체분산체 제제는 난용성 약물인 pranlukast의 용해도와 생체이용률을 개선하는데 유용하게 응용될 것으로 기대된다.

In this study, poly(ethylene glycol) (PEG) was used as a hydrophilic polymer carrier to develop solid dispersion formulations for enhancing solubility and dissolution rate of pranlukast, one of poorly soluble drugs that has been broadly used for the treatment of asthma. PEG based solid dispersions with or without poloxamer were prepared by hot melting and solvent evaporation methods. The resultant solid dispersions were characterized by DSC and powder X-ray measurements, and their morphological properties were observed to be partially changed to amorphous state with reduced crystallinity. Dissolution and solubility tests showed that the solubility and dissolution rate of the solid dispersions were significantly enhanced. The solid dispersion formulation prepared by the hot melting method with a chemical composition of pranlukast:PEG:poloxamer = 1:5:1 demonstrated the most enhanced solubility and dissolution rate. The results suggest that the solid dispersions based on PEG and poloxamer are promising systems for the enhancement of solubility and bioavailability of pranlukast.

Keywords:pranlukast;poly(ethylene glycol);poloxamer;solid dispersion;hot melting;solubility.

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Newman SP, Hollingsworth A, Clark AR, Int. J.Pharm., 102, 127 (1994)
Murakoshi H, Saotome T, Fujii Y, Ozeki T, Takashima Y, Yuasa H, Okada H, J. Drug Del. Sci. Tech., 15, 223 (2005)
Asker AF, Whitworth CW, Pharmazie., 30, 530 (1975)
Perng CY, Kearney AS, Patel K, Palepu NR, Zuber G, Int. J. Pharm., 176, 31 (1998)
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[Referenced By]

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[1] Horter D, Dressman JB, Adv. Drug Deliv. Rev., 46, 75 (2001)

[2] van Drooge DJ, Hinrichs WLJ, Visser MR, Frijlink HW, Int. J. Pharm., 310, 220 (2006)

[3] Merisko-Liversidge E , Liversidge GG, Cooper ER, Eur. J. Pharm. Sci., 18, 113 (2003)

[4] Rasenack N, Hartenhauer H, Muller BW, Int. J. Pharm., 254, 137 (2003)

[5] Rasenack N, Muller BW, Pharm. Res., 19, 1894 (2002)

[6] Imai T, Nishiyama T, Ueno M, Otagiri M, Chem. Pharm.Bull., 37, 2251 (1989)

[7] Taniguchi Y, Tamura G, Honma M, Aizawa T, Maruyama N, Shirato K, Takishimal T, J. Allergy. Clin. Immunol., 92, 507 (1993)

[8] Graham G, Giles R, Grinter T, Hayler J, Howie S, Johnson G, Mann I, Novack V, Oxley P, Quick J, Smith N, Synth.Commun., 27, 1065 (1997)

[9] Tanaka N, Imai K, Okimoto K, Ueda S, Tokunaga Y, Ibuki R, Higaki K, Kimura T, J. Control. Release., 112, 51 (2006)

[10] Ohara T, Kitamura S, Kitagawa T, Terada K, Int. J.Pharm., 302, 95 (2005)

[11] Pouton CW, Eur. J. Pharm. Sci., 29, 278 (2006)

[12] Leuner C, Dressman J, Eur. J. Pharm. Sci., 50, 47 (2000)

[13] Craig DQM, Int. J. Pharm., 231, 131 (2002)

[14] Ohara T, Kitamura S, Kitagawa T, Terda K, Int. J. Pharm., 302, 95 (2005)

[15] Bikiaris D, Papageorgiou GZ, Stergiou A, Pavlidou E, Karavas E, Kanaze F, Georgarakis M, Thermochim. Acta, 439(1-2), 58 (2005)

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

[17] Tran TT, Tran PH, Lee B, Eur. J. Pharm. Biopharm.

[18] Sekiguchi K, Obi N, Chem. Pham. Bull., 9, 866 (1961)

[19] Walker GM, Holland CR, Ahmad MMN, Craig DQM, Chem. Eng. Sci., 60(14), 3867 (2005)

[20] Sethia S, Squillante E, Int. J. Pharm., 272, 1 (2004)

[21] Newman SP, Hollingsworth A, Clark AR, Int. J.Pharm., 102, 127 (1994)

[22] Murakoshi H, Saotome T, Fujii Y, Ozeki T, Takashima Y, Yuasa H, Okada H, J. Drug Del. Sci. Tech., 15, 223 (2005)

[23] Asker AF, Whitworth CW, Pharmazie., 30, 530 (1975)

[24] Perng CY, Kearney AS, Patel K, Palepu NR, Zuber G, Int. J. Pharm., 176, 31 (1998)

[25] Khan GM, Zhu JB, Drug Dev. Ind. Pharm., 24, 455 (1998)

[26] Lee JH, Kopecek J, Andrade JD, J Biomed. Mater. Res., 23, 351 (1989)

[27] Majerik V, Charbit G, Badens E, Horvath G, Szokonya L, Bosc N, Teillaud E, J. Supercrit. Fluids, 40(1), 101 (2007)