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定制药物剂量的可调模块设计:以逐渐减少抗抑郁药物为例。

Tailor-Made Doses of Pharmaceuticals by Tunable Modular Design: A Case Study on Tapering Antidepressant Medication.

机构信息

Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, Copenhagen, 2100, Denmark.

Oral Product Development, Pharmaceutical Technology & Development, AstraZeneca, Gothenburg, 431 83, Sweden.

出版信息

Adv Mater. 2024 Jul;36(30):e2403852. doi: 10.1002/adma.202403852. Epub 2024 May 15.

Abstract

An abrupt cessation of antidepressant medication can be challenging due to the appearance of withdrawal symptoms. A slow hyperbolic tapering of an antidepressant, such as citalopram hydrobromide (CHB), can mitigate the withdrawal syndrome. However, there are no viable dosage forms on the market to implement the tapering scheme. A solution using a tunable modular design (TMD) approach to produce flexible and accurate doses of CHB is proposed. This design consists of two parts: 1) a module with a fixed amount of preloaded CHB in a freeze-dried polymer matrix, and 2) fine-tuning the CHB dose by inkjet printing. A noncontact food-grade printer, used for the first time for printing pharmaceuticals, is modified to allow for accurate printing of the highly concentrated CHB ink on the porous CHB-free or CHB-preloaded modules. The produced modules with submilligram precision are bench-marked with commercially available CHB tablets that are manually divided. The TMD covers the entire range of doses needed for the tapering (0.5-23.8 mg). The greatest variance is 13% and 88% when comparing the TMD and self-tapering, respectively. Self-tapering is proven inaccurate and showcases the need for the TMD to make available accurate and personalized doses to wean off treatment with CHB.

摘要

由于会出现戒断症状,突然停止使用抗抑郁药物可能具有挑战性。缓慢双曲线式逐渐减少抗抑郁药(如氢溴酸西酞普兰)的剂量可以减轻戒断综合征。但是,市场上没有可行的剂型来实施这种逐渐减少的方案。本研究提出了一种使用可调模块设计(TMD)来生产灵活且准确剂量的氢溴酸西酞普兰的解决方案。该设计由两部分组成:1)一个装有固定数量预先加载的氢溴酸西酞普兰的冻干聚合物基质的模块;2)通过喷墨打印微调氢溴酸西酞普兰的剂量。一种非接触式食品级打印机,首次用于打印药物,经过改装后可以在无孔或预加载有氢溴酸西酞普兰的模块上精确打印高浓度的氢溴酸西酞普兰墨水。以市售的手动分割的氢溴酸西酞普兰片剂为基准,精确到亚毫克级的生产模块具有良好的基准性。TMD 涵盖了逐渐减少剂量所需的整个范围(0.5-23.8 mg)。与 TMD 相比,自减剂量的最大差异分别为 13%和 88%。自减剂量证明是不准确的,这表明需要 TMD 来提供准确和个性化的剂量,以逐渐减少氢溴酸西酞普兰的治疗。

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