강제유화에 의한 Poly(3-hydroxy butyrate-co-3-hydroxy valerate) 미립자의 제조

이기창; 이성은; 서형주; Ki-Chang Lee; Sung-Eun Lee; Hyeong-Joo Seo

Polymer(Korea), Vol.23, No.3, 338-347, May, 1999

Export Citation

강제유화에 의한 Poly(3-hydroxy butyrate-co-3-hydroxy valerate) 미립자의 제조

Preparation of Poly(3-hydroxy butyrate-co-3-hydroxy valerate) Microspheres by Emulsification Process

이기창^†, 이성은, 서형주

경상대학교 고분자공학과 & 생산기술연구소

Ki-Chang Lee^†, Sung-Eun Lee, and Hyeong-Joo Seo

Department of Polymer Sci. & Eng., RII, Gyeongsang National University, Jinju 660-701, Korea

E-mail:

초록

서방성 의약제 지지체로서 사용할 poly(3-hydroxy butyrate-co-3-hydroxy valerate) [poly(3HB-co-3HV)]미립자 및 미립자덩어리를 다야한 강제유화 조건과 용매증발법에 의해 제조하였다. 이온계 계면활성제인 HTMAB 와 SLS를 입자안정제로 사용한 겨우 ultrasonication 과 homogenizer 유화장치하에서 0,2-0,3 ㎛의 입자경을 갖는 우유와 같은poly(3HB-co-3HV)와 PHBFKXPRTM가 제조되었다. 일반적으로 유화제농도와 교반속도 및 교반시간이 증가함에 따라 입자경은 감소하였으며 고분자용액의 농도와 점도가 증가함에 따라 입자경은 증가하였다. 반면에 비이온계 계면활성제인 gelatine과 PVA를 입자안정제로 사용했을 경우 교반속도에 따라 다양한 입자크기와 입자형태의 poly(3HB-co-3HV) D600G 미립자가 제조되었다. 즉, 600-900 rpm의 3blade propeller 교반기를 사용하였을 경우 각각 4-385 ㎛과 8-242 ㎛ 입자경 범위의 둥근입자가 생성하였으며 6000-10000 rpm의 Omni mixer를 사용할 경우 각각 0.6-60 ㎛과 1-67 ㎛범위의. sub-micron 크기의 둥근 입자들의 회합에 의해 생성한 입자덩어리가 생성되었다.

In order to prepare poly(3HB-co-3HV) microspheres as polymeric supports for the uses of controlled drug delivery, various artificial emulsifications with solvent evaporation were carried out. In case of using HTMAB or SLS as an ionic surfactant under ultrasonication and homogenizer, milky-white poly(3HB-co-3HV) and PHB latices with average particle diameter of 0.2-0.3 ㎛ were made. In general, average particle diameter decreased with increasing concentration of surfactant, agitation speed, agitation time, and increased with increasing concentration of polymer solution and its viscosity. On the other hand, in case of using gelatine or PVA as a nonionic surfactant, various sizes and types of poly(3HB-co-3HV)D600G particles were prepared depending on the agitation speed, that is, spherical particles of diameter ranges of 4-385 ㎛ and 8-242 ㎛, respectively, were formed at 600-900 rpm using 3 blade propeller, and particle-aggregates, consisting of aggregation of sub-micron size particles. of diameter ranges of 0.6-60 ㎛ and 1-67 ㎛, respectively, were formed at 6000-10000 rpm when using Omni mixer.

Keywords:controlled drug release;poly(3HB-co-3HV);artificial emulsification;particle-aggregates;ionic and nonionic surfactant

[References]

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[1] Doi Y, Abe C, Macromolecules, 23, 3705 (1990)

[2] Doi Y, "Microbial Polyesters," VCH Publishers, Inc,. U.S.A. (1990)

[3] Lee YH, Polym. Sci. Technol., 2(5), 319 (1991)

[4] Lee DH, Polym. Sci. Technol., 2(5), 332 (1991)

[5] Lafferty RM, Korsatko B, Korsatko W, "Microbial Production of Poly(β-hydroxybutyric acid)," in "Biotechnology(A Comprehensive Treatise)," eds. by H.J. Rehm and G. Reed, vol. 6b, VCH Publishers, Inc, Federal Republic of Germany (1988)

[6] "Properties and Processing of Biopol," Monsanto Plc (1996)

[7] Scholes PD, Coombes AGA, Davies MC, Illum L, Davis SS, "Particle Engineering of Biodegradable Colloids for Site-Specific Drug Delivery," in "Controlled Drug Delivery," , ed. by K. Park, ACS Professional Reference Book, Washington, D.C. (1997)

[8] Sparer RV, Shih CS, Ringeisen CD, Himmelstein KJ, J. Control. Release, 1, 23 (1984)

[9] Makino K, Arakawa M, Kondo T, Chem. Pharm. Bull., 33(3), 1195 (1985)

[10] Jalil R, Nixon JR, J. Microencapsul., 7(3), 297 (1990)

[11] Conti B, Pavanetto F, Genta I, J. Microencapsul., 9(2), 153 (1992)

[12] Yoshikawa H, Ikada Y, Chem. Pharm. Bull., 37(3), 802 (1989)

[13] Arshady R, J. Control. Release, 17, 1 (1991)

[14] Niwa T, Takeuchi H, Kawashima Y, J. Control. Release, 25, 89 (1993)

[15] Ammoury N, Benita S, J. Pharm. Sci., 79(9), 763 (1990)

[16] Juni K, Nakano M, Kubota M, J. Control. Release, 4, 25 (1986)

[17] El-Aasser MS, "Latex Preparations by Direct Miniemulsification of Polymer Solutions and Polymerization of Monomer Miniemulsions," in "Advances in Emulsion Polymerization and Technology," ed. by M.S. El-Aasser(Lehigh University), Emulsion Polymers Institute, Bethelehem (1990)

[18] Horowitz DM, Sanders JK, J. Am. Chem. Soc., 116(7), 2695 (1994)

[19] Song J, Shin Y, Yoon S, J. Microbiol. Biotechnol., 3(2), 123 (1993)

[20] McCutcheon's, "Emulsifiers and Detergents," vol. 1, North American Edition, MC Publishing Co., NJ, U.S.A. (1996)