DOI QR코드

DOI QR Code

Development of trans-cinnamaldehyde self-microemulsifying drug delivery system(SMEDDS) with superior stability

안정성이 우수한 신남알데히드 자가미세유화 약물전달시스템 개발

  • Bang, Kyu-Ho (Department of Pharmaceutical Engineering, Gyeongnam National University of Science and Technology) ;
  • Kim, Kyeong Soo (Department of Pharmaceutical Engineering, Gyeongnam National University of Science and Technology)
  • 방규호 (경남과학기술대학교 제약공학과) ;
  • 김경수 (경남과학기술대학교 제약공학과)
  • Received : 2019.10.08
  • Accepted : 2019.12.06
  • Published : 2019.12.31

Abstract

This study was undertaken to develop a stable self-microemulsifying drug delivery system (SMEDDS) for trans-cinnamaldehyde, a known antibacterial and antifungal agent. A simultaneous analytical method was established for quantification of trans-cinnamaldehyde and its degradant, cinnamic acid. Various surfactants were applied to assess their effect on the aqueous solubility of trans-cinnamaldehyde, and pseudo-ternary phase diagrams were plotted. Of the various formulations tested, the liquid SMEDDS composed of trans-cinnamaldehyde (oil), Cremophor EL (surfactant) and Transcutol P (cosurfactant) at a volume ratio of 10/70/20, produced the smallest emulsion droplet size (around 23 nm). The stability test determined the superior stability of the trans-cinnamaldehyde SMEDDS with constant trans-cinnamaldehyde content and z-average diameter of emulsion, under accelerated and heat stressed condition. Thus, we believe that this novel trans-cinnamaldehyde SMEDDS formulation has the potential to be applied for the development of trans-cinnamaldehyde medicines in the pharmaceutical industry.

본 연구의 목적은 다양한 항균활성을 지닌 천연물 유래 물질 신남알데히드를 이용한 안정한 자가미세유화 약물전달시스템을 개발하는 것이다. 이러한 목표를 달성하기 위하여 신남알데히드의 주 분해산물인 신남산과 신남알데히드의 동시 정량법을 확립하였으며, 설정된 분석법을 이용한 용해도 시험으로 신남알데히드에 대한 용해도 개선효과가 우수한 계면활성제를 선별하였다. 계면활성제로 Cremophor EL, 공계면활성제로 Transcutol P를 이용한 신남알데히드의 pseudo-ternary phase diagram을 작성하여 에멀전의 입자크기를 최소화시킬 수 있는 조성비로 신남알데히드 : Cremophor EL : Trasncutol P = 10 : 70 : 20%(v/v/v)인 SMEDDS 조성물을 제조한 후 안정성 시험을 통해 신남알데히드의 함량변화 및 에멀전의 입자크기 변화에 대해 확인하였다. 본 연구를 통해 제조된 신남알데히드의 자가유화 나노에멀전은 신남산의 생성량이 적고 신남알데히드의 함량 저하 속도가 느려 안정성이 우수하였으며, 안정성 기간 중에 최초의 입자크기를 잘 유지하는 특성이 확인되었다. 따라서 이 조성물은 신남알데히드를 위한 의약품 제형으로의 활용 가능성이 높을 것으로 사료된다.

Keywords

References

  1. S. Ashakirin, M. Tripathy, U. K. Patil, A. Baker, A. Majeed, "Chemistry and bioactivity of cinnamaldehyde : a natural molecule of medicinal importance", International Journal of Pharmaceutical Sciences and Research, Vol.8, No.6, pp.2333-2340, 2017. DOI: http://dx.doi.org/10.13040/IJPSR.0975-8232.8(6).2333-40
  2. K-H. Bang, D-W. Lee, H-M. Park, Y-H. Rhee, "Inhibition of Fungal Cell Wall Synthesizing Enzymes by trans -Cinnamaldehyde", Bioscience, biotechnology and biochemistry, Vol.64, No.5, pp.1061-1063, 2000. DOI: https://doi.org/10.1271/bbb.64.1061
  3. A. Arfa, L. Preziosi-Belloy, P. Chalier, N. Gontard, "Antimicrobial Paper Based on a Soy Protein Isolate or Modified Strach Coating Including Carvacrol and Cinnamaldehyde", Agricultural and food chemistry, Vol.55, No.6, pp.2155-2162, 2007. DOI: https://doi.org/10.1021/jf0626009
  4. K-H. Bang, Y-H. Lee, B-S. Min, "Purification and properties of an antifungal component, AF-001, from Cinnamomi Cortex", The Korean Journal of Mycology, Vol.25, No.4, pp.348-353, 1997.
  5. E. Chen, S. Wu, D. McClements, B. Li, Y. Li, "Influence of pH and cinnamaldehyde on the physical stability and lipolysis of whey protein isolate-stabilized emulsions", Food Hydrocolloids, Vol.69, pp.103-110, 2017. DOI: https://doi.org/10.1016/j.foodhyd.2017.01.028
  6. A. Sail, W. Mustapha, S. Yusop, M. Maskat, A.Shamsuddin, "Optimisation of Cinnamaldehyde-in -water Nanoemulsion Formulation using Central Composite Rotatable Design", Sains Malaysiana, Vol.47, No.9, pp.1999-2008, 2018. DOI: http://dx.doi.org/10.17576/jsm-2018-4709-07
  7. D. Kim, J. Cho, J. Park, Jung. Kim, E. Song et al., "Self-microemulsifying drug delivery system(SMEDDS) for improved oral delivery and photostability of methotrexate", International Journal of Nanomedicine, Vol.14, pp.4949-4960, 2019. DOI: https://doi.org/10.2147/IJN.S211014
  8. W-L. Tian, L-L. Lei, Q. Zhang, Y. Li, "Physical Stability and Antimicrobial Activity of Encapsulated Cinnamaldehyde by Self-Emulsifying Nanoemulsion", Journal of Food Process Engineering, Vol.39, No.5, pp.462-471, 2016. DOI: https://doi.org/10.1111/jfpe.12237
  9. O. Mustapha, K. Kim, S. Shafique, D. Kim, S. Jin et al., "Development of novel cilostazol-loaded solid SMEDDS using a SPG-membrane emulsification technique: Physicochemical characterization and in vivo evaluation", Colloids and Surfaces B: Biointerfaces, Vol.150, pp.216-222, 2017. DOI: https://doi.org/10.1016/j.colsurfb.2016.11.039
  10. K. Kim, J. Kim, S. Jin, D. Kim, D. Kim et al., "Development of novel prasugrel base microsphereloaded tablet with enhanced stability: Physicochemical characterization and in vivo evaluation in beagle dogs", Colloids and Surfaces B: Biointerfaces, Vol.146, pp.754-761, 2016. DOI: http://dx.doi.org/10.1016/j.colsurfb.2016.07.025
  11. H. Moon, A. Yousaf, K. Cho, C. Yong, J. Kim et., "Evaluation of stability and simultaneous determination of fimasartan and amlodipine by a HPLC method in combination tablets", Asian Journal of Pharmaceutical Sciences, Vol.9, pp.123-128, 2014. DOI: https://doi.org/10.1016/j.ajps.2014.04.002
  12. C. Pouton, "Lipid formulation for oral administration of drugs: non-emulsifying, self-emulsifying and 'self-microemulsifying' drug delivery systems", European Journal of Pharmaceutical Sciences, Vol.11, pp.93-98, 2000. DOI: https://doi.org/10.1016/S0928-0987(00)00167-6
  13. L. Li, C. Zhou, Z. Xu, "Self-nanoemulsifying drug-delivery system and solidified self -nanoemulsifying drug-delivery system", Nanocarriers for Drug Delivery, pp.421-449, 2019. DOI: https://doi.org/10.1016/B978-0-12-814033-8.00014-X
  14. K. Bouchemal, S. Briancon, E. Perrier, H. Fessi, "Nano-emulsion formulation using spontaneous emulsification: solvent, oil and surfactant optimisation", International Journal of Pharmaceutics, Vol.280, pp.241-251, 2004. DOI: https://doi.org/10.1016/j.ijpharm.2004.05.016
  15. A. Singh, A. Chaurasiya, M. Singh, S. C. Upadhya, R. Mukherjee et al.,, "Exemestane Loaded Self- Microemulsifying Drug Delivery System (SMEDDS): Development and Optimization", AAPS PharmSciTech, Vol.9, pp.628-634, 2008. DOI: https://doi.org/10.1208/s12249-008-9080-6
  16. A. Sprunk, C. Strachan, A. Graf, "Rational formulation development and in vitro assessment of SMEDDS for oral delivery of poorly water soluble drugs", European Journal of Pharmaeutical Sciences, Vol.46, pp.508-515, 2012. DOI: http://dx.doi.org/10.1016/j.ejps.2012.04.001
  17. D. Patel, K. Sawant, "Self Micro-Emulsifying Drug Delivery System: Formulation Development and Biopharmaceutical Evaluation of Lipophilic Drugs", Current Drug Delivery, Vol.6, pp.419-424, 2009. DOI: https://doi.org/10.2174/156720109789000519
  18. P. Balakrishnan, B-J. Lee, D. Oh, J. Kim, Y. Lee et al., "Enhanced oral bioavailability of Coenzyme Q10 by self-emulsifying drug delivery systems", International Journal of Pharmaceutics, Vol.374, pp.66-72, 2009. DOI: https://doi.org/10.1016/j.ijpharm.2009.03.008
  19. H. Zayas, N. Truong, D. Valade, Z. Jia, M. Monteiro, "Narrow molecular weight and particle size distributions of polystyrene 4-arm stars synthesized by RATF-mediated miniemulsions", Polymer Chemistry, Vol.4, pp.592-599, 2013. DOI: https://doi.org/10.1039/c2py20709e