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Design and characterization of drug release-modulating injectable gel depot
- Alternative Title
- Munsik Jang
- Author(s)
- 장문식
- Alternative Author(s)
- Munsik Jang
- Advisor
- 이범진
- Department
- 일반대학원 약학과
- Publisher
- The Graduate School, Ajou University
- Publication Year
- 2020-02
- Language
- eng
- Keyword
- hydrogel; injectable
- Alternative Abstract
- Abstract The objective of this study is to develop pyridoxal phosphate (PLP) modulated injectable gel depot of aripiprazole (ARP) with controlled gelation time and sustained release for 14 days. In this study, ARP was chosen as a model drug. PLP was used to control gelation time of alginate hydrogel and glucono-delta-lactone (GDL) was used for gelation triggering agent. When only alginate and calcium carbonate (CaCO3) exist in solution, gelation doesn’t occur due to the very low solubility of CaCO3. GDL is hydrolyzed in aqueous solution, slowly lowering the pH and increasing the solubility of CaCO3. As a result, gelation occurs by reaction of alginate and calcium cations released from CaCO3. PLP can combines with calcium cations to form pyridoxal calcium phosphate to control the gelation time by lowering the concentration of free calcium cations. The injectability of sol state before gelation was investigated with a syringe. The physicochemical properties of hydrogel were evaluated by using fourier transform infrared spectroscopy (FT-IR) and scanning electron microscope (SEM). Moreover, swelling ratio, in-vitro degradation ratio, stiffness and drug release profiles of hydrogel were also characterized. The sustained release of ARP was executed in phosphate buffer saline (pH 7.4) containing 0.25 % SLS under incubation in water bath (37°C, 50 rpm) for 14 days. Stability of the optimal formulation in sol state, before adding GDL solution, was conducted at 25℃ for 1 month by measuring viscosity. The appropriate gelation time of 1 minute 30 seconds, 3 minutes 40 seconds and 9 minutes was obtained when GDL and PLP were used at a ratio of 1:1.555 (0.18:0.28), 1:2 (0.14:0.28) and 1:1.666 (0.18:0.3), respectively. When the amount of GDL was fixed, the gelation time became longer as PLP increased. The sol state before gelation was found to be injectable with a syringe. The hydrogel with the ratio of GDL to PLP of 1:1.666 (0.18:0.3) degraded slowly compared to other 2 formulations and had rigidity value of 3.55 ± 0.060 kPa, slightly lower than muscle. The sustained release effect was maximized when the GDL and PLP was used at a ratio of 1:1.666 (0.18:0.3). As GDL and PLP increased respectively, the sustained release effect improved. The hydrogel successfully released aripiprazole for 14 days. The optimal hydrogel formulation with gelation time of 9 minutes and the highest sustained release effect showed constant viscosity in sol state after storage at 25°C for 1 month.
- Fulltext
- Appears in Collections:
- Graduate School of Ajou University > Department of Pharmacy > 3. Theses(Master)
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