Preparation of Polycaprolactone Microcapsules by Membrane Emulsification Method and Its Drug Release Properties

막유화법에 의한 생분해성 Polycaprolactone 마이크로캡슐의 제조와 약물방출 특성

  • Youm, Kyung-Ho (School of Chemical Engineering, College of Engineering, Chungbuk National University) ;
  • Yun, Tae-Ho (School of Chemical Engineering, College of Engineering, Chungbuk National University) ;
  • Kim, Kong-Soo (School of Chemical Engineering, College of Engineering, Chungbuk National University) ;
  • Cho, Suh-Hyeong (Department of Medical Materials, Hyejeon College)
  • 염경호 (충북대학교 공과대학 화학공학부) ;
  • 윤태호 (충북대학교 공과대학 화학공학부) ;
  • 김공수 (충북대학교 공과대학 화학공학부) ;
  • 조석형 (혜전대학 의료재료과)
  • Published : 2007.03.30

Abstract

Uniform microcapsules containing ionic model drugs were prepared by controlling various conditions of emulsification procedure using a lab-scale membrane emulsification system with a SPG (Shirasu porous glass) tubular membrane. We observed the effects of various emulsification parameters [concentration and molecular weight of polycaprolatone (PCL) polymer, transmembrane pressure and emulsifier concentration in disperse phase and continuous phase, stirring speed] on the mean size and size ditribution of microcapsules containing lidocaine hydrochloride (cationic drug), sodium salicylate (nonionic drug) and 4-acetaminophen (anionic drug) used as a model drugs. Also, release characteristics of a model drugs from PCL microcapsules were investigated. Controlling membrane emulsification parameters, uniform PCL microcapsules with about $5\;{\mu}m$ of the mean size were finally prepared. The release rate and the burst effect of microcapsules were decreased in condition of the acidic solution, but it was increased in condition of the base solution.

SPG (Shirasu porous glass) 관형 막이 설치된 회분식 막유화 장치를 사용하여 이온성 약물이 담지된 단분산 polycaprolactone (PCL) 마이크로캡슐을 제조하기 위한 막유화 공정변수의 최적조건을 결정하였다. 마이크로캡슐에 담지된 이온성 약물로는 양이온성인 lidocaine-hydrochloride, 중성인 sodium salicylate와 음이온성인 4-acetaminophen의 3가지를 사용하였으며, PCL 마이크로캡슐로부터 이들 모델약물의 방출거동을 검토하였다. 캡슐제조에 사용된 PCL의 농도와 분자량, 막간 압력차, 분산상과 연속상에 첨가시킨 유화제의 농도, 연속상의 교반속도가 막유화법으로 제조된 PCL 캡슐의 크기와 크기분포에 미치는 영향을 검토하였다. 이들 공정변수의 조절을 통해 평균 크기 약 $5\;{\mu}m$의 균일한 마이크로캡슐을 제조할 수 있었다. 약물 방출실험 결과 산성조건에서 알칼리조건으로 방출환경이 변화됨에 따라 약물 방출속도가 증가하였다.

Keywords

References

  1. Z. Haque and J. E. Kinsella, 'Emulsifying properties of food proteins and bovine serum albumin', J. Food Sci., 53, 416 (1988) https://doi.org/10.1111/j.1365-2621.1988.tb07719.x
  2. D. J. McClements, 'Food Emulsions: Principles, Practice, and Techniques', CRC Press, Chapter 1, 1 (1999)
  3. E. Dickinson, 'Emulsions and droplet size control', in: D. J. Wedlock (Ed.), 'Controlled Particle, Droplet and Bubble Formation', Butterworth-Heinemann, Oxford, Chapter 7, 189 (1994)
  4. T. Nakahima, M. Shimizu, and M. Kukizaki, 'Membrane emulsification by microporous glass', Key Engineering Materials, 61-62, 513 (1991)
  5. S. M. Joscelyne and G. Tragardh, 'Membrane emulsification -a literature review', J. Memb. Sci., 169, 107 (2000) https://doi.org/10.1016/S0376-7388(99)00334-8
  6. S. Omi, 'Preparation of monodisperse microspheres using the shirasu porous glass emulsification technique', Colloids and Surfaces A: Physicochem. Eng. Aspects, 109, 97 (1996) https://doi.org/10.1016/0927-7757(95)03477-3
  7. P. A. Kramer, 'Albumin microspheres as vehicles for achieving specificity in drug delivery', J. Parm. Sci., 63, 1646 (1974) https://doi.org/10.1002/jps.2600631044
  8. E. Celikkaya, E. B. Denkbas, and E. Piskin, 'Poly( DL-lactide)/poly(ethylene glycol) copolymer particles. I. Preparation and characterization', J. Appl. Polym. Sci., 61, 1439 (1996) https://doi.org/10.1002/(SICI)1097-4628(19960829)61:9<1439::AID-APP2>3.0.CO;2-K
  9. K. Juni, J. Ogata, M. Nalano, T. Ichihara, M. Mori, and M. Akagi, 'Preparation and evaluation in vitro and in vivo of polylactic acid microsperes containing doxorubicin', Chem. Pharm. Bull., 33, 313 (1985) https://doi.org/10.1248/cpb.33.313
  10. V. Schroder, O. Behrend, and H. Schubert, 'Effect of dynamic interfacial tension on the emulsification process using microporous ceramic membranes', J. Colloid and Interface Science, 202, 334 (1998) https://doi.org/10.1006/jcis.1998.5429
  11. R. A. Williams, S. J. Peng, D. A. Wheeler, N. C. Morley, D. Taylor, M. Whalley, and D. W. Houldsworth, 'Controlled production of emulsions using a crossflow membrane Part II: Industrial scale manufacture', Trans IChemE, 76, Part A, 902 (1998) https://doi.org/10.1205/026387698525702
  12. S. Nagashima, M. Koide, S. Ando, K. Makino, T. Tsukamoto, and H. Ohshima, 'Surface properties of monodisperse poly(acrylamide-co-acrylic acid) hydrogel microspheres prepared by a membrane emulsification technique', Colloids and Surfaces A:Physiochem. Eng. Aspects, 153, 221 (1999)
  13. Y. H. Choi, D. E. Wiley, and K. H. Youm, 'Preparation of alginate microspheres using membrane emulsification method', Membrane J., 14(3), 218 (2004)
  14. A. Berthoid, K. Cremer, and J. Kreuter, 'Preparation and characterization of chitosan microspheres as drug carrier for prednisolone sodium phosphate as model for anti-inflammatory drugs', J. Control. Rel., 39, 17 (1996) https://doi.org/10.1016/0168-3659(95)00129-8
  15. C. G. Pitt, T. A. Marks, and A. Shimdler, 'Controlled release of bioactive materials', Academic Press, Chapter 1, 19 (1980)
  16. H. Jaffe, P. A. Giang, D. K. Hayes, J. A. Miller, and B. H. Stroud, 'Controlled release pesticides and pharmaceuticals', Plenum Press, 303 (1981)
  17. C. G. Pitt, M. M. Gratzl, and A. R. Jeffcoat, J. Pharm. Sci, 68, 1534 (1979) https://doi.org/10.1002/jps.2600681219
  18. V. Schroeder, O. Behrend, and H. Schubert, 'Effect of dynamic interfacial tension on the emulsification process using microporous, ceramic membranes', J. Colloid and Interface Sience, 202(2), 334 (1998) https://doi.org/10.1006/jcis.1998.5429