臺灣博碩士論文加值系統

微乳液是由水、油、界面活性劑和輔助界面活性劑在適當比例下組成的系統，大約在70年前被發現，其具有良好的透明外觀、自發性形成、容易製備和熱穩定性等優異特性，此外，微乳液還可以增加活性成分對皮膚的滲透，因此被廣泛的使用在許多領域，包括了化粧品、生物醫藥、食品工業等。

本研究的途徑為：(1)採用對皮膚無刺激性、安全性高的非離子型界面活性劑 (Tween 20、Tween 40和Tween 80)，(2)以廣泛應用於化粧品的多元醇（丙二醇、丁二醇和甘油）做為輔助界面活性劑，與短鏈醇（丙醇和丁醇）做比較，及(3)研究界面活性劑和輔助界面活性劑在不同的比例（1:1、 2:1、 3:1、 4:1 和1:0) 下，(4) 不同的油脂（中鏈甘油三酯、荷荷芭油和礦物油）所做出來的效果，最後獲得微乳液系統最佳的三相圖。

這項研究的結果顯示：Tween 80、甘油、水和甘油三酯（MCT）的系統能產生最大的微乳液區域，界面活性劑和輔助界面活性劑最佳的比例是4:1，而且此微乳液系統中也囊括有水中油型和油中水型的乳化體。最後，利用濁度計、導電度計以及奈米粒徑分析儀來輔助證明實驗結果的準確性。另外，將微乳液儲存在不同的溫度（4℃、40℃和室溫）下進行12個循環的觀察，也發現在選定的區域中都能保持穩定，具備良好之安定性。

雖然利用甘油所獲得的微乳液區域大小並不如傳統短鏈醇，但其安全性和氣味等條件卻較佳，也能同時滿足兩種乳化型態的需求，因此，這些透明微乳液具有良好的發展前景，可應用於個人美容保健用品與生醫材料的開發上。

Microemulsion is composed of oil, water, and a mixture of surfactant and cosurfactant with a proper ratio. Microemulsions were found about seventy years ago and were used in several fields including cosmetics, biomedical industry, and food industry due to their good transparent appearance, spontaneous formation, ease of preparation and thermodynamic stability. Moreover, microemulsions can increase skin permeation of the cosmetic substances.

The approach of this study was to use appropriate nonionic surfactants (Tween 20, Tween 40 and Tween 80) which are non-irritating and safe towards the skin, and to investigate the influence of polyols as cosurfactants (propylene glycol, butylene glycol, and glycerin) which are widely used in cosmetics comparing with short chain alcohols (propanol and butanol). We also studied the effect of surfactant-to-cosurfactant ratio (with various weight ratios of 1:1, 2:1, 3:1, 4:1 and 1:0) and different oils (Medium-chain triglycerides; MCT, Jojoba oil, and Mineral oil) on the pseudo-ternary phase diagram and further to optimize the microemulsion system.

The results of this research show that the system compose of Tween 80, glycerin, water and medium-chain triglycerides (MCT) could found the largest microemulsion area. The best Tween 80 to glycerin ratio for microemulsion preparation was 4:1. Furthermore, this microemulsion system also includes water in oil and oil in water microemulsion. Turbidity, conductivity and particle size measurement were to further confirm the microemulsion area. The selected microemulsion remained stable during storage in different temperature (4°C, 40°C and room temperature) for 12 cycles.

Despite using glycerin as cosurfactant formed a smaller area of microemulsion than using short-chain alcohols in pseudo-ternary phase diagram, it is safe-to-use and has a better odor. In addition, this microemulsion system consists of two types of microemulsion that can satisfy our needs. Therefore, this transparent microemulsion has good prospects for development. It can be applied to personal care products and biomedical materials in the future.

ACKNOWLEDGEMENT I
ABSTRACT (CHINESE) II
ABSTRACT (ENGLISH) IV
TABLE OF CONTENTS VI
LIST OF FIGURES IX
LIST OF TABLES XIII

1. INTRODUCTION 1
1.1 Microemulsions 1
1.2 Type of microemulsion 5
1.3 Component of microemulsion system 7
1.3.1 Surfactant 7
1.3.1.1 Hydrophilic−Lipophilic Balance (HLB) 9
1.3.1.2 Classification of surfactants 12
1.3.2 Cosurfactant 21
1.3.3 Oil phase 23
1.3.4 Aqueous phase 26
1.4 Pseudo ternary phase diagram 26
1.5 Microemulsions in cosmetics 29
1.6 Aim of the Study 30

2. MATERIALS AND METHODS 31
2.1 Materials 31
2.2 Instruments 32
2.3 Methods 33
2.3.1 Selection of surfactants 33
2.3.2 Effect of cosurfactants 37
2.3.3 Effect of surfactant-to-cosurfactant ratio 38
2.3.4 Effect of oils 39
2.3.5 Construction of pseudo-ternary phase diagram 40
2.3.6 Particle size and conductivity measurements 40
2.3.7 Stability study 41

3. RESULTS AND DISCUSSION 42
3.1 Pseudo-ternary phase diagrams 42
3.1.1 Selection of surfactants 42
3.1.2 Effect of cosurfactants 47
3.1.3 Effect of surfactant-to-cosurfactant ratio 53
3.1.3.1 Effect of Tween 80-to-n-Butanol ratio 53
3.1.3.2 Effect of Tween 80-to-Glycerin ratio 58
3.1.4 Effect of oils 62
3.2 Choosing the best system 65
3.3 Microemulsion characterization 65
3.4 Particle size measurement 69
3.5 Stability study 69

4. CONCLUSION 72

5. REFERENCES 73

袁美英，礦物油在非離子型界面活性劑之微乳化現象，靜宜女子大學應用化學研究所，1992.
Danielsson, I., Lindman, B. The definition of microemulsion. Colloids and Surfaces. 1981; 3: 391-392.
Kumar, P., Mittal, K.L. Handbook of Microemulsion Science and Technology. Marcel Dekker. 1999.
Rosano, H.L., Clausse, M. Microemulsion systems. Surfactant science series volume 24. 1987.
Hoar, T.P., Schulman, J.H. Transparent water in oil dispersions: the oleopathic hydromicelle. Nature. 1943; 152: 102-103.
Schulman, J.H., Stoeckenius, W., Prince, L.M. Mechanism of formation and structure of microemulsions by electron microscopy. Journal of Chemical Physics. 1959; 63:1677-1680.
Shinoda, K., Lindman, B. Organised surfactant systems: Microemulsions. Langmuir. 1987; 3: 135–149.
Ceglie, A., Das, K.P., Lindman, B. Effect of oil on the microscopic structure in four component cosurfactants microemulsions. Colloids and Surfaces. 1987; 28: 29-40.
Paul, B.K., Moulik, S.P. Microemulsions: an overview. Journal of Dispersion Science and Technology. 1997; 18: 301-367.
Lawrencea, M.J., Reesb, G.D. Microemulsion-based media as novel drug delivery systems. Advanced Drug Delivery Reviews. 2000; 45: 89–121.
Hellweg, T. Phase structure of microemulsions. Current Opinion in Colloid and Interface Science. 2002; 7: 50-56.
Chaudhari, V.M., Patel, M.S., M. R. Patel. Microemulsion Based Gel: A Review. International Journal of Universal Pharmacy and Bio Sciences. 2014; 3(4): 63-78.
Siddheshwar, S.S., Wadghule, P.B., Waghmare, G.A.,Varpe, P.S., Vikhe, D.N. Microemulsion: New Approach for protection of Pleasant Smell in Pharmaceuticals. International Journal of Chemistry and Pharmaceutical Sciences. 2014; 2(4): 807-814.
Agrawal, O.P., Agrawalb, S. An Overview of New Drug Delivery System: Microemulsion. Asian Journal of Pharmaceutical Science & Technology. 2012; 1(2): 5-12.
Critical Micelle Concentration of Surfactant, Mixed Surfactant and Polymer by Different Methods at Room Temperature and Its Importance. Kinetic Studies of Some Esters and Amides in Presence of Micelles. 55-105.
Oremusova, I.J., C.S.C., Lengyel., P.D.A. Critical Micelle Concentration of Ionic Surfactants. 1-6.
Maqsood, A.M., Mohd, A.H., Firdosa, N., Shaeel, A.AL-T., Zaheer, K. Anti-corrosion Ability of Surfactants: A Review. International Journal of Electrochemical Science. 2011; 6: 1927-1948.
Griffin, W.C. Classification of Surface Active Agents by HLB. Journal of the Society of Cosmetic Chemists. 1949; 1: 311-326.
Griffin, W.C. Calculation of HLB valuess of Nonionic Surfactants. Journal of the Society of Cosmetic Chemists. 1954; 5: 249-256.
Mehta, S.K., Kaur, G. Microemulsions: Thermodynamic and Dynamic Properties. InTech. 2011.
Gadhave, A. Determination of Hydrophilic-Lipophilic Balance Value. International Journal of Science and Research. 2014; 3(4): 573-575.
Allen, L.V., Popovich, N.G., Ansel, H.C. Ansel’s Pharmaceutical Dosage form and Drug Delivery System. Wolters Kluwer/Lippincott Williams & Wilkins. 2014.
Israelachvili, J.N. The science and applications of emulsions: an overview. Colloids and Surfaces A: Physicochemical and Engineering Aspects. 1994; 91: 1-8.
The HLB System a time-saving guide to emulsifier selection. ICI Americas Inc. 1980.
Holmberg K., Jonsson B., Kronberg B., Lindman B. Surfactants and Polymer in Aqueous Solution. John Wiley & Sons, Inc. 2003.
Myers, D. Surfactant Science and Technology. John Wiley & Sons, Inc. 2005.
Jahan, K., Balzer, S., Mosto, P. Toxicity of nonionic surfactant. WIT Transactions on Ecology and the Environment. 2008; 110: 281-292.
Boonme, P. Uses of microemulsions as novel vehicles in skin care products. HPC Today. 2009; 3(2): 18-20.
O'Hagan, D.T., Singh, M. A safe and potent oil-in-water emulsion adjuvant. Vaccine Adjuvants and Delivery Systems. 2007; 115-118.
Molecular structure and HLB value of surfactants (Tween series), Chemical structures of cosurfactants, and Medium-chain triglycerides (MCT). www.wikipedia.org
Lv, F. F., Zheng, L.Q., Tung, C.H. Studies on the stability of the chloramphenical in the microemulsion free alcohols. European Journal of Pharmaceutics and Biopharmaceutics. 2006; 62: 288-294.
Roux, D., Coulon, C. Modelling Interactions in Microemulsion Phases. Journal de Physique. 1986; 47: 1257- 1264.
Flanagan, J., Singh, H. Microemulsions: a potential delivery system for bioactives in food. Critical Reviews in Food Science and Nutrition. 2006; 46: 221-237.
Syed, H.K., Peh, K.K. Identification of phases of various oil, surfactant/cosurfactants and water system by ternary phase diagram. Acta Poloniae Pharmaceutica - Drug Research. 2014; 71(2): 301-309.
Ghosh, P.K., Murthy, R.S.R. Microemulsions: A potential drug delivery system. Current Drug Delivery. 2006; 3: 167-180.
Tsuji, H., Kasai, M., Takeuchi, H., Nakamura, M., Okazaki, M., Kondo, K. Dietary medium-chain triacylglycerols suppress accumulation of body fat in a double-blind, controlled trial in healthy men and women. Journal of Nutrition. 2001; 131: 2853-2859.
Babayan, V.K. Medium-chain triglycerides-their composition, preparation, and application. Journal of the American Oil Chemists' Society. l968; 45: 23-5.
Enig, M.G. Know Your Fats: The Complete Primer for Understanding the Nutrition of Fats, Oils and Cholesterol. Bethesda Press. 2000.
Qizwini, H.A.L., Khateeb, E.A.L., Mhaidat, N.M. Study of Jordanian Jojoba (Simmonsia Chinensis) Liquid Wax by GC and GC/MS. European Scientific Journal. 2014; 10(30): 278-293.
Divijak, J.M., Jr. Production of Technical White Mineral Oil. US Patent 3,629,096. Assigned to Atlantic Richfield Company, US. 1967.
Nash, J.F., Gettings, S.D., Diembeck, W., Chudowski, M., Kraus, A.L. A toxicological review of topical exposure to white mineral oils. Food and Chemical Toxicology. 1996; 34: 213-225.
Chemical structures of Jojoba oil www.jojobacompany.com/what-jojoba
Chemical structures of Mineral oil www.concawe.eu/uploads/Modules/MCMedias/1411648530910/s2-1_hedelin_final-2013-02353-01-e.pdf
Kumar. K. Senthil, Dhachinamoorthi. D, Saravanan. R; Microemulsions as Carrier for Novel Drug Delivery: A Review. International Journal of Pharmaceutical Sciences Review and Research. 2011; 10: 37-45.
Shafiq-un-Nabi, S., Shakeel, F., Talegaonkar, S., Ali, J., Baboota, S., Ahuja, A., Khar, R.K., Ali, M. Formulation development and optimization using nanoemulsion technique: A technical note. Journal of the American Association of Pharmaceutical Scientists. 2007; 8(2): E1-E6.
Sharma, G.R. Chapter5: Preparation, optimization and characterization of microemulsions. 2013; 166-202.
Ritika, Harikumar, L.S., Aggarwal, G. Microemulsion system in role of expedient vehicle for dermal application. Journal of Drug Delivery & Therapeutics. 2012; 2(4): 23-28.
Shaji, J., Reddy, M.S. Microemulsions as drug delivery systems. Pharma Times. 2004; 36(7): 17 – 24.
Boonme, P. Applications of microemulsions in cosmetics. Journal of Cosmetic Dermatology. 2007; 6: 223-228.
Barel, A.O., Paye, M., Maibach, H.I. Handbook of Cosmetic Science and Technology. Taylor & Francis Group. 2006.
Bidyut, K.P., Satya, P.M. Uses and applications of microemulsions. Current Science. 2001; 80(8): 990-1001.
Mahdi, E.S., Sakeena, M.H.F., Abdulkarim, M.F., Abdullah, G.Z., Sattar, M.A., Noor, A.M. Effect of surfactant and surfactant blends on pseudoternary phase diagram behavior of newly synthesized palm kernel oil esters. Drug Design, Development and Therapy. 2011; 5: 311–323.
Sjoblom, J., Lindberg, R., Friberg, S.E. Microemulsions – phase equilibria characterization, structures, applications and chemical reactions. Advances in Colloid and Interface Science. 1996; 65: 125–187.
Porras, M., Solans, C., González, C., Gutiérrez, J.M. Properties of water-in-oil (W/O) nano-emulsions prepared by a low-energy emulsification method. Colloids and Surfaces A: Physicochemical and Engineering Aspects. 2008; 324(1–3): 181–188.