Journal of the Korean Applied Science and Technology (한국응용과학기술학회지)

The Korean Society of Applied Science and Technology (한국응용과학기술학회)
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Stabilization of Tocopheryl Acetate of Swollen Micelle by Poloxamer

Poloxamer를 이용한 Swollen Micelle의 Tocopheryl Acetate 안정화

  • Kim, Mi-Seon (Department of Chemistry and Cosmetics, College of National Science, Jeju National University) ;
  • Yoon, Kyung-Sup (Department of Chemistry and Cosmetics, College of National Science, Jeju National University)
  • 김미선 (제주대학교 화학.코스메틱스학과) ;
  • 윤경섭 (제주대학교 화학.코스메틱스학과)
  • Received : 2019.05.30
  • Accepted : 2019.06.28
  • Published : 2019.06.30
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Abstract

When the surfactant is dissolved in an aqueous solution, it forms aggregate called micelles (<20 nm) in the solution, and micelles can form the solubilized formulation by supporting the active ingredient therein. Swollen micelles are formulations capable of carrying larger amounts of active ingredient than conventional solubilized formulations at 50~100 nm. Unlike liposomes or nanoemulsions, which require a separate process such as high pressure emulsification, Swollen micelle is a more efficient method of solubilization and particle formation from a productive point of view. In this study, stabilization experiments on swollen micelle formulations were carried out using poloxamer 407, and then optimized formulation experiments for tocopheryl acetate components were performed using Response Surface Methodology (RSM). Tocopheryl acetate, a surfactant that affects solubilization and an active substance, were set as a factor and the correlation between them was confirmed. As the evaluation method, stability and particle size distribution and size were confirmed by temperature and time, and the structure and shape of the swollen micelle carrying the active ingredient were confirmed by FIB. These results show that poloxamer 407 0.500%, octyldodeceth-16 0.387% and tocopheryl acetate 0.945% are the most optimized prescriptions for swollen micelle stabilized with tocopheryl acetate.

계면활성제가 수용액 중에 용해되면 용액 내에서 micelle (< 20 nm) 이라는 응집체를 형성하며, micelle은 그 내부에 활성물질을 담지하여 가용화 제형이 형성될 수 있다. Swollen micelle은 50~100 nm 정도로 일반 가용화 제형보다 더 많은 양의 활성물질을 담지할 수 있는 제형이다. Swollen micelle은 고압유화와 같은 별도의 공정이 필요한 liposome이나 nanoemulsion과는 달리 특별한 공정이 필요 없어 생산적인 면에서 좀 더 효율성 있는 가용화 및 입자형성 방법이라고 할 수 있다. 본 연구에서는 Poloxamer 407을 이용하여 swollen micelle 제형에 대한 안정화 실험을 진행한 후, Response Surface Methodology (RSM)을 이용하여 tocopheryl acetate 가용화에 대한 제형 최적화 실험을 진행하였다. 가용화에 영향을 주는 계면활성제와 활성물질인 tocopheryl acetate를 요인(factor)로 설정하고 서로 간의 상관관계를 확인하였다. 평가방법으로서 온도 및 시간에 따른 안정성과 입자 분포 및 크기를 확인하였으며, FIB를 통해 효능 물질을 담지한 swollen micelle의 입자 구조 및 모양을 확인하였다. 이러한 실험 결과들을 통하여 tocopheryl acetate를 안정화시킨 swollen micelle은 poloxamer 407 0.500%, octyldodeceth-16 0.387%, tocopheryl acetate 0.945%일 때 가장 최적화된 처방이라 할 수 있다.

Keywords

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Fig. 1. Particle form of micelle and swollen micelle.

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Fig. 2. Structure of poloxamer 407 (approximate block lengths of a = 101 and b = 56).

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Fig. 3. Manufacturing method of swollen micelle.

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Fig. 4. Results of prescription for various solubilizers affecting solubilization in Table 2.

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Fig. 5. Results of prescription for changes in content of poloxamer 407 and Octyldodeceth-16 in Table 3.

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Fig. 6. Results of tocopheryl acetate solubilization for changes in content of poloxamer 407 and Octyldodeceth-16 in Table 4.

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Fig. 7. Box-Behnken design, The point at the center of the cube corresponds to the center of the Box-Behnken design, and the point at the middle of each line of the cube corresponds to the IBFact.

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Fig. 8. 3D model for particle size of RSM (A: poloxamer 407, B: octyldodeceth-16, C: tocopheryl acetate / (a): AB, (b): AC, (c): BC).

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Fig. 9. 3D model for PDI of RSM (A: poloxamer 407, B: octyldodeceth-16, C: tocopheryl acetate / (d): AB, (e): AC, (f): BC).

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Fig. 10. 3D model for Zeta potential of RSM (A: poloxamer 407, B: octyldodeceth-16, C: tocopheryl acetate / (g): AB, (h): AC, (i): BC).

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Fig. 11. Stability comparison of swollen micelles after 30 days.

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Fig. 12. Turbidity comparison of swollen micelles after 30 days. Rating: 1-10 (the higher the score, the higher the turbidity).

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Fig. 13. Cyro-SEM image (left: Run 13 / right: Run 16)

Table 1. Information about the raw materials used in the experiment

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Table 2. Prescription experiment for solubilizers affecting solubilization

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Table 3. Solubilization prescription experiments on Poloxamer 407 content changes

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Table 4. Tocopheryl acetate solubilization experimental prescription

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Table 5. Setting and scope of independent variables as RSM factors

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Table 6. Experiments on RSM factor range of 17 prescriptions

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Table 7. Y-axis variable results for 17 experiments using Box-Behnken design

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Table 8. Variance analysis for Y axis variable data

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Table 9. Coefficient table to 3D model of variance analysis (A : Poloxamer 407 / B : octyldodeceth-16 / C : tocopheryl acetate)

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Table 10. Optimal condition setting using RSM

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