Xiao Tao, Yang Quanzhu, Chen Lusi, Xie Jiayu, Zhong Huiying, Zhang Guoqing, He Haibing, Liu Hongfei
College of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang, 330004, China.
College of Pharmacy and Food Engineering, Wuyi University, Jiangmen, 529020, China.
AAPS PharmSciTech. 2025 Apr 29;26(5):118. doi: 10.1208/s12249-025-03111-w.
Atomoxetine hydrochloride (ATH) is a first-line medication used to treat Attention Deficit Hyperactivity Disorder (ADHD) in children. However, it poses challenges such as a bitter taste and difficulties in dose adjustment. While once-daily administration may result in excessive drug exposure, twice-daily dosing improves plasma drug concentration stability but can reduce patient compliance, especially in school-aged children. To address these challenges, a novel strategy was proposed that involves encapsulating ATH into ion exchange resins (IERs) (referred to as ATH@IER). The pH-responsive release of ATH from the ATH@IER exhibited a limited release rate in neutral conditions, effectively masking the bitter taste, which was evaluated through electronic tongue analysis. The cation-responsive release of ATH from the ATH@IER demonstrated immediate-release (IR) property, which was combined with Eudragit RS100 coated ATH@IER (ATH@MC) to establish a biphasic release system. ATH orally disintegrating tablets (ATH ODT) were manufactured using a composition of ATH@IER and ATH@MC (40:60, w/w), along with other excipients. Pharmacokinetic studies demonstrated that a single dose of ATH ODT produced a bimodal plasma concentration, resulting in a two-fold decrease in peak concentration (C) while maintaining an unchanged area under the drug concentration-time curve (AUC) compared to the commercial ATH oral solution administered once. Notably, the plasma drug concentration of ATH ODT remained steadier than that of the commercial product when administered twice. In conclusion, ATH ODT represents a promising formulation that effectively masks bitter taste and provides biphasic release for the treatment of ADHD.
盐酸托莫西汀（ATH）是用于治疗儿童注意力缺陷多动障碍（ADHD）的一线药物。然而，它存在一些挑战，如苦味和剂量调整困难。虽然每日一次给药可能导致药物暴露过量，但每日两次给药可提高血浆药物浓度稳定性，但会降低患者依从性，尤其是在学龄儿童中。为应对这些挑战，提出了一种新策略，即将ATH封装到离子交换树脂（IERs）中（称为ATH@IER）。通过电子舌分析评估，ATH从ATH@IER中的pH响应释放显示在中性条件下释放速率有限，有效掩盖了苦味。ATH从ATH@IER中的阳离子响应释放表现出速释（IR）特性，将其与Eudragit RS100包衣的ATH@IER（ATH@MC）结合建立了双相释放系统。使用ATH@IER和ATH@MC（40:60，w/w）的组合物以及其他辅料制备了ATH口腔崩解片（ATH ODT）。药代动力学研究表明，单剂量的ATH ODT产生双峰血浆浓度，与单次给药的市售ATH口服溶液相比，峰浓度（C）降低了两倍，同时药物浓度-时间曲线下面积（AUC）保持不变。值得注意的是，当每日给药两次时，ATH ODT的血浆药物浓度比市售产品更稳定。总之，ATH ODT是一种有前景的制剂，可有效掩盖苦味并提供双相释放用于治疗ADHD。
