Preparation and characterization of injectable in-situ forming gel based on lipid liquid crystal for one month delivery of aripiprazole: In-vitro and in-vivo evaluations in rats

阿立哌唑 甘油 体内 化学 生物利用度 药物输送 色谱法 溶剂 药理学 有机化学 医学 精神分裂症(面向对象编程) 生物 生物技术 精神科
作者
Malihe Karimi,Shayan Azimi-Hashemi,Elham Khodaverdi,Marzieh Mohammadi,Farhad Eisvand,Adeleh Rahbardar-Khorasani,Rahim Nosrati,Hossein Kamali
出处
期刊:Journal of Drug Delivery Science and Technology [Elsevier BV]
卷期号:96: 105640-105640 被引量:5
标识
DOI:10.1016/j.jddst.2024.105640
摘要

The present study developed a one-month sustained-release formulation of aripiprazole, used for the treatment of schizophrenia and bipolar disorder, based on lipid liquid crystal (LLC) using phosphatidylcholine (PC) and N-methyl-2-pyrrolidone (NMP) solvent with sorbitan monooleate (SMO) or derivative glycerol oleate (glycerol monooleate (GMO), glycerol di-oleate (GDO), and glycerol trioleate (GTO)). The best formulation was selected based on the minimum initial burst release and the highest release of aripiprazole during the 30-day period. So, the formulations containing GMO and SMO exhibited the best initial slow release, while the other two formulations showed a burst release within 24 h. Furthermore, the GMO formulation did not release the drug completely during the 30-day study period, and the formulation containing GTO released the drug completely in less than a month. Therefore, the two formulations containing SMO and GDO were selected for further tests. The prepared liquid crystals had a hexagonal structure, indicating the creation of a suitable formulation structure with slow and controlled release. The area under the curve for the LLC-SMO formulation was higher than for other formulations, supporting the sustained release of aripiprazole and improving the long-term bioavailability of the drug. Moreover, this formulation was found to be safe and did not cause any damage to the skin at the injection site or vital organs such as the spleen, kidney, brain, heart, and liver. Hence, it can be considered a suitable option for developing an extended-release LLC formulation of aripiprazole.
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