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Fattigation design for long-acting formulations of quetiapine
- Author(s)
- NGUYEN DINH HY
- Advisor
- Beom-Jin, Lee
- Department
- 일반대학원 약학과
- Publisher
- The Graduate School, Ajou University
- Publication Year
- 2022-08
- Language
- eng
- Keyword
- PLGA; Quetiapine; fattigation platform; fatty acid chain length; long-acting formulation; nanoparticles; pH-triggered self-assembly
- Alternative Abstract
- 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.
- Fulltext
- Appears in Collections:
- Graduate School of Ajou University > Department of Pharmacy > 3. Theses(Master)
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