표제지
목차
1. 소개(Introduction) 11
1.1. 경구투여, 약물 용해도 및 용출률 11
1.2. 티카그렐러(Ticagrelor) 12
1.3. 난용성 약물의 가용화 기술 12
1.4. 고체분산체 13
1.5. 자가나노유화 약물전달시스템(Self-nanoemulsifying drug delivery system, SNEDDS) 13
1.6. 연구의 목적 14
2. 재료 및 방법(Materials and Methods) 14
2.1. 시약 및 기기 14
2.2. 용해도 시험 15
2.3. 티카그렐러가 함유된 고체분산체 제조 16
2.4. Pseudo-ternary phase diagrams 16
2.5. SNEDDS 제조 및 입자 크기 측정 17
2.6. 티카그렐러가 함유된 고형의 SNEDDS 제조 17
2.7. 티카그렐러가 함유된 고형의 SNEDDS 물성 평가 17
2.8. 물리 화학적 특성 평가 18
2.9. 용출시험 19
2.10. 티카그렐러 고체분산체 함유 정제의 제조 19
2.11. 비교용출시험 19
3. 결과 및 고찰(Results and Discussion) 20
3.1. 가용화제의 선정 20
3.2. 티카그렐러가 함유된 고체분산체 제조 21
3.3. Pseudo-ternary phase diagrams 23
3.4. SNEDDS 제조 및 입자 크기 측정 23
3.5. 티카그렐러가 함유된 고형의 SNEDDS 제조 24
3.6. 티카그렐러 함유 정제의 제조 26
4. 결론(Conclusion) 26
5. 참고문헌(References) 28
국문 초록 72
ABSTRACT 74
Table 1. Composition of various solvent-evaporated solid dispersions and surface-attached... 66
Table 2. Composition of various solvent-evaporated solid dispersions. 67
Table 3. Physical properties of liquid SNEDDS. 68
Table 4. Composition of ticagrelor-loaded solid SNEDDSs. 69
Table 5. Flow properties of solid SNEDDSs. 70
Table 6. Physical properties of solid SNEDDSs. 71
Fig. 1A. Schematic illustration of solid dispersion. 37
Fig. 1B. Schematic illustration of solvent-evaporated solid dispersion method. 37
Fig. 1C. Schematic illustration of surface-attached solid dispersion method. 37
Fig. 2. Solubility of ticagrelor in 1% polymer solution. Each value represents the mean ± S.D. 38
Fig. 3A. Solubility of ticagrelor in 10% surfactant solution. Each value represents the mean ± S.D. 39
Fig. 3B. Screening of weight ratio of ticagrelor to selected surfactant: (A) Solutol HS15 (B)... 40
Fig. 4. Solubility of ticagrelor in 100% oil. Each value represents the mean ± S.D. 41
Fig. 5. Solubility of ticagrelor in solvent-evaporated solid dispersions and surface attached... 42
Fig. 6A. Solubility of ticagrelor in solvent-evaporated solid dispersions. Each value represents... 43
Fig. 6B. Release profiles of ticatrelor-loaded solvent-evaporated solid dispersion in water. Each... 44
Fig. 7A. Solubility of ticagrelor in solvent-evaporated solid dispersions. Each value represents... 45
Fig. 7B. Release profiles of ticatrelor-loaded solvent-evaporated solid dispersion in water. Each... 46
Fig. 8A. Scanning electron microscope images: (A) Ticagrelor (x1,000), (B) SE1 (x5,000), (C)... 47
Fig. 8B. Scanning electron microscope images: (A) Ticagrelor (x1,000), (B) SE5 (x100), (C)... 48
Fig. 9A. Powder X-ray diffraction patterns: (A) Ticagrelor, (B) Kollidon VA64, (C) Physical... 49
Fig. 9B. Powder X-ray diffraction patterns: (A) Ticagrelor, (B) Kollidon VA64, (C) Poloxamer... 50
Fig. 10A. Differential scanning calorimetry thermograms: (A) Ticagrelor, (B) Kollidon VA64,... 51
Fig. 10B. Differential scanning calorimetry thermograms: (A) Ticagrelor, (B) Kollidon VA64,... 52
Fig. 11. Pseudo-ternary phase diagram. 53
Fig. 12A. Effect of oil/surfactant ratio on liquid SNEDDS emulsion droplet size. Each value... 54
Fig. 12B. Effect of oil/surfactant/co-surfactant ratio on liquid SNEDDS emulsion droplet size.... 55
Fig. 13. Particle size distribution of Liquid SNEDDS (without drug) and Liquid SNEDDS(with drug). 56
Fig. 14. Scanning electron microscope images: (A) Ticagrelor (x1,000), (B) SS1 (x500), (C)... 57
Fig. 15A. Powder X-ray diffraction patterns: (A) Ticagrelor, (B) Silicon dioxide, (C) Physical... 58
Fig. 15B. Powder X-ray diffraction patterns: (A) Ticagrelor, (B) Calcium silicate, (C) Physical... 59
Fig. 15C. Powder X-ray diffraction patterns: (A) Ticagrelor, (B) Magnesium aluminometa... 60
Fig. 16. Differential scanning calorimetry thermograms: (A) Ticagrelor, (B) Silicon dioxide,... 61
Fig. 17. Transmission electron microscopy image of ticagrelor-loaded solid SNEDDS. 62
Fig. 18. Release profiles of ticatrelor-loaded solid SNESSDs in water. Each value represents... 63
Fig. 19A. Release profiles of ticagrelor from the commercial ticagrelor tablet, the SE7 powder... 64
Fig. 19B. Release profiles of ticagrelor from the commercial ticagrelor tablet, SE7 tablet: (A)... 65