Fattigation design for long-acting formulations of quetiapine
- 주제(키워드) Quetiapine , fattigation platform , fatty acid chain length , pH-triggered self-assembly , PLGA , nanoparticles , long-acting formulation.
- 주제(DDC) 615.1
- 발행기관 아주대학교
- 지도교수 Beom-Jin, Lee
- 발행년도 2022
- 학위수여년월 2022. 8
- 학위명 석사
- 학과 및 전공 일반대학원 약학과
- 실제URI http://www.dcollection.net/handler/ajou/000000032065
- 본문언어 영어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
목차
Chapter 1. Fattigation design of quetiapine for pH-triggered self-assembly and controlled release using different chain lengths of fatty acids 1
1 Introduction 1
2 Materials and methods 5
2.1 Materials 5
2.2 Synthesis and characterization of quetiapine-fatty acid conjugates 6
2.3 Solubility and LogP of quetiapine fumarate and quetiapine-fatty acid conjugates 7
2.4 Cleavage kinetics in human plasma and human liver fraction 8
2.5 Quantification of quetiapine, QD, QM and QS by HPLC-UV 8
2.6 Cell viability 9
2.7 Effect of pH and the concentration of quetiapine-fatty acid conjugates on their self-assembly property 10
2.8 Critical micelle concentration of quetiapine-fatty acid conjugates in pH 1.2 11
2.9 Preparation and characterization of quetiapine-fatty acid nanosuspensions 11
2.10 Stability of quetiapine-fatty acid nanosuspensions 13
2.11 Release kinetics of quetiapine-fatty acid nanosuspensions 13
2.12 Statistics 14
3 Results and Discussion 15
3.1 Synthesis and characterization of quetiapine-fatty acid conjugates 15
3.2 Solubility and logP of quetiapine fumarate and quetiapine-fatty acid conjugates 18
3.3 Cleavage kinetics in human plasma and in human liver fraction 20
3.4 Cell viability 23
3.5 Self-assembly of quetiapine-fatty acid conjugates in acidic environments 25
3.6 Effect of quetiapine-fatty acid conjugates on their self-assembly property 26
3.7 Critical micelle concentration of quetiapine-fatty acid conjugates in pH 1.2 30
3.8 Characterization of quetiapine-fatty acid nanosuspensions 32
3.9 Stability of quetiapine-fatty acid nanosuspensions 35
3.10 Effect of fatty acid chain length on the drug release from quetiapine-fatty acid nanosuspensions 37
4 Conclusion 40
Supplementary Data 41
Chapter 2. Quetiapine-myristic acid conjugate loaded poly (lactic-co-glycolic acid) nanoparticles with particle size reduction for long-acting injection 47
1 Introduction 47
2 Materials and methods 50
2.1 Materials 50
2.2 Preparation of PLGA nanoparticles (PLGA NPs) 51
2.3 Characterization of PLGA NPs 51
2.4 Loading capacity, drug content and encapsulation efficiency 52
2.5 Injectability test 53
2.6 In vitro drug release 53
2.7 Stability of PLGA NPs 54
2.8 Cell viability 55
2.9 Statistics 56
3 Results and discussion 57
3.1 Preparation and characterization of PLGA NPs 57
3.2 Loading capacity, drug content and encapsulation efficiency 60
3.3 Injectability test 62
3.4 In vitro drug release 65
3.5 Stability 68
3.6 Cell viability 70
4 Conclusion 73
References 74