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Fattigation design for long-acting formulations of quetiapine
| DC Field | Value | Language |
|---|---|---|
| dc.contributor.advisor | Beom-Jin, Lee | - |
| dc.contributor.author | NGUYEN DINH HY | - |
| dc.date.accessioned | 2022-11-29T03:01:24Z | - |
| dc.date.available | 2022-11-29T03:01:24Z | - |
| dc.date.issued | 2022-08 | - |
| dc.identifier.other | 32065 | - |
| dc.identifier.uri | https://dspace.ajou.ac.kr/handle/2018.oak/21126 | - |
| dc.description | 학위논문(석사)--아주대학교 일반대학원 :약학과,2022. 8 | - |
| dc.description.tableofcontents | 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 | - |
| dc.language.iso | eng | - |
| dc.publisher | The Graduate School, Ajou University | - |
| dc.rights | 아주대학교 논문은 저작권에 의해 보호받습니다. | - |
| dc.title | Fattigation design for long-acting formulations of quetiapine | - |
| dc.type | Thesis | - |
| dc.contributor.affiliation | 아주대학교 일반대학원 | - |
| dc.contributor.department | 일반대학원 약학과 | - |
| dc.date.awarded | 2022. 8 | - |
| dc.description.degree | Master | - |
| dc.identifier.localId | T000000032065 | - |
| dc.identifier.uci | I804:41038-000000032065 | - |
| dc.identifier.url | https://dcoll.ajou.ac.kr/dcollection/common/orgView/000000032065 | - |
| dc.subject.keyword | PLGA | - |
| dc.subject.keyword | Quetiapine | - |
| dc.subject.keyword | fattigation platform | - |
| dc.subject.keyword | fatty acid chain length | - |
| dc.subject.keyword | long-acting formulation | - |
| dc.subject.keyword | nanoparticles | - |
| dc.subject.keyword | pH-triggered self-assembly | - |
| dc.description.alternativeAbstract | Chapter 1. This study aimed to design a novel controlled release nanoparticle system of quetiapine to overcome its short half-life and low bioavailability based on the fattigation technique. Quetiapine-fatty acid conjugates with different carbon chain lengths of 10, 14 and 18 carbons were synthesized before they were self-assembled in pH 1.2 to form nanosuspensions (QDN, QMN and QSN, respectively). The conjugate with longer fatty acid possessed higher lipophilicity and a lower conversion rate to quetiapine in human plasma and liver extraction. While pH and proton-to-quetiapine ratio (mol/mol) were critical attributes in nanoparticle preparation, the physicochemical properties of the obtained nanosuspensions (particle size, stability and dissolution profile) also depended on the carbon chain length of fatty acids. In pH 1.2 with the proton-to-quetiapine ratio of 0.75, all QDN, QMN and QSN bore positive charges with average diameters of around 250, 180 and 150 nm, respectively. QMN had a prolonged release profile over one month without initial burst or delayed-release patterns. This sustained-release system can be developed further as a long-acting formulation of quetiapine for better patient compliance and treatment effectiveness. Chapter 2. This study aims to investigate the use of poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) as a long-acting system with better injectability for quetiapine to improve patient compliance with this antipsychotic drug. Poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) loading with quetiapine-myristic acid conjugate (QM) was prepared by an emulsion-diffusion method using a high-speed homogenizer. The minuscule particle size of 200-300 nm of nanoparticles was injectable using a thin gauge needle (26G) and offered a less painful injection than commercial microspheres. The interaction between drug and polymer matrix regulated the drug loading efficiency, toxicity and release kinetic of PLGA NPs. Due to the stronger hydrophobic-hydrophobic interaction with the PLGA matrix, QM possessed higher encapsulation efficiency (98%) and loading capacity (33%) than the reference of quetiapine (60% and 20%, respectively). The PLGA NPs loading with QM demonstrated a prolonged drug release over one month without huge burst release that was compatible with myoblast cells. This biocompatible controlled release system could be potentially developed as an LAI formulation of quetiapine. | - |
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