Yu Panpan, Zhang Mengjun, Jin Xiong, Wu Keheng, Long Sihui, Cheng Shishi, Fu Long, Xu Xiao, Liu Jie, Liu Dan, Li Xue, Liu Bo, Xu Jian
Livzon Pharmaceutical Group Inc., Livzon Corporate, Zhuhai, Guangdong, China.
School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, Wuhan, China.
Front Pharmacol. 2025 Jul 9;16:1507828. doi: 10.3389/fphar.2025.1507828. eCollection 2025.
Long-acting injectable formulations, such as paliperidone palmitate extended-release injectable suspension, have been designed to release medicines slowly and sustainably. Developing models that simulate drug release from long-acting injectable formulations is challenging. A novel approach to modeling and simulating complex and multiphasic drug pharmacokinetics (PK) is provided in this article to facilitate development of long-acting formulations. By segmenting nanocrystalline particles according to their different sizes, the absorption delays of each segment were obtained from the results of the PK study in dogs. In addition to the lag time for each segment, all other parameters, including physicochemical parameters such as drug solubility, density and diffusion coefficient, as well as pharmacokinetic parameters related to clearance, elimination and distribution, were introduced into the model to establish a muscle compartment model for use in humans. By using this model, the injectable suspensions paliperidone samples were predicted to have a long release of 90-100 days .
长效注射制剂，如棕榈酸帕利哌酮缓释注射混悬液，旨在缓慢且持续地释放药物。开发模拟长效注射制剂药物释放的模型具有挑战性。本文提供了一种模拟复杂多相药物药代动力学（PK）的新方法，以促进长效制剂的开发。通过根据纳米晶体颗粒的不同大小进行分段，从犬类PK研究结果中获得了各段的吸收延迟。除了各段的滞后时间外，所有其他参数，包括药物溶解度、密度和扩散系数等物理化学参数，以及与清除、消除和分布相关的药代动力学参数，都被引入模型中，以建立用于人体的肌肉室模型。通过使用该模型，预测帕利哌酮注射混悬液样本的长效释放时间为90 - 100天。
