Optimization of complex coacervation by central composite design (CCD) : microcapsules of vitamin U using multiple emulsion method
중심계획법을 이용한 복합 코아세르베이션의 최적화 : 다중유화법을 이용한 비타민 U의 마이크로캡슐
- 약학대학 약학과
- Issue Date
- 서울대학교 대학원
- Complex coacervation; Microcapsule; Vitamin U; Multiple emulsion; Response surface methodology; Central composite design
- 학위논문 (석사)-- 서울대학교 대학원 약학대학 약학과, 2017. 8. 김대덕.
The purpose of this study was to prepare microcapsules encapsulating hydrophilic vitamin U (VU, methylmethionine sulfate chloride, MMSC) using complex coacervation. The composition of these particles was optimized using central composite design (CCD), which is one of response surface methodology (RSM), and characterized.
Since the complex coacervation reaction is known as a useful method for encapsulating hydrophobic materials, multiple emulsion method and s/o dispersion method were introduced for encapsulating highly water-soluble vitamin U (clogP = -1.7072, Chemdraw®, cambridgesoft). A ratio of gelatin and gum arabic which are compoenents in particle (X1, weight of gelatin / weight of gum arabic) and a volume of oil phase (X2) were set as two variables to optimize acquired weight of microcapsules (Y1) to maximize and to obtain a VU content of more than 2.5% in microcapsule (Y2). Microcapsules prepared under optimal conditions were analyzed for identifying their properties using an optical microscope, a fluorescence microscope, a scanning electron microscope, a DSC and a laser diffraction particle size analyzer. Odor of VU was quantitatively identified using a headspace-gas chromatograph / mass spectrometer (HS-GC / MS).
Results & Discussion
When the microcapsules were prepared by applying the s / o dispersion method, a VU content was very low (0.001 ± 0.0003%). Thus, the compositon of microcapsules using multiple emulsion method was optimized. When the microcapsules were actually prepared under optimal conditions, the predicted Y1 and Y2 values corresponded to their actual measured values over 95%. Therefore, It can be concluded that this model was well designed.
The morphology of microcapsules encapsulating multiple emulsion was identified by using the optical microscope and the fluorescence microscope. In addition, the SEM image of internal particle also indicated that the microcapsule encapsulated multiple emulsion. However, as a result of the analysis using a laser diffraction particle size analyzer, the size was not uniform (average particle size 79.17 ± 69.82 μm) and showed a wide particle size distribution. The DSC results showed that the materials that constitute the particles (vitamin U, transglutaminase, and gelatin) exist in an amorphous state in the coacervate microcapsules. The amount of dimethylsulfide, which is the cause of vitamin U odor, was analyzed by HS-GC/MS. As a result, the amount of dimethysulfide detected in microcapsules containing 6.25 mg of vitamin U was DMS generated from about 70 mg of vitamin U powder. This suggests that the microcapsule manufacturing process affected the stability of vitamin U, and further studies are needed to improve it.
The hydrophilic vitamin U was successfully encapsulated in the coacervate microcapsules using the multiple emulsion method, and the DoE technique was found to be a useful method for finding the optimum condition. It is believed that the formulation is applicable to cosmetics and pharmaceuticals in the future.