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Development of Child-Friendly Lisdexamfetamine Chewable Tablets Using Ion Exchange Resin as a Taste-Masking Carrier Based on the Concept of Quality by Design (QbD)

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  • Advancements in Modified-release Oral Drug Delivery - Delivery throughout the Gastro-intestinal Tract
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Abstract

Taste masking is critical to improving the compliance of pediatric oral dosage forms. However, it is challenging for extremely bitter lisdexamfetamine dimesylate (LDX) with a long half-life and given in large dose. The present study aims to develop an immediate-release, taste-masked lisdexamfetamine chewable tablet. Lisdexamfetamine-resin complexes (LRCs) were prepared using the batch method. The molecular mechanism of taste masking was explored by PXRD, PLM, STA, and FT-IR. The results showed that taste masking was attributed to the ionic interaction between drug and the resin. The ion exchange process conformed to first-order kinetics. The rate-limiting step of drug release was the diffusion of ions inside the particles, and the concentration of H+ was the key factor for immediate release. The masking efficiency of the prepared LRCs in saliva exceeded 96%, and the drug could be completely released within 15 min in aqueous HCl (pH 1.2). Furthermore, the SeDeM expert system was used for the first time to comprehensively study the powder properties of LRCs and to quickly visualize their defects (compressibility, lubricity/stability, and lubricity/dosage). The selection of excipients was targeted rather than traditional screening, thus obtaining a robust chewable tablet formulation suitable for direct compression. Finally, the difference between chewable tablets containing LRCs and chewable tablets containing lisdexamfetamine dimesylate was compared by in vitro dissolution test, electronic tongue, and disintegration test. In conclusion, an immediate-released, child-friendly lisdexamfetamine chewable tablets without bitterness was successfully developed by the QbD approach, using the SeDeM system, which may help in further development of chewable tablets.

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Authors and Affiliations

  1. China State Institute of Pharmaceutical Industry, 285 Gebaini Road, Shanghai, 201203, China

    Chunmei Zhu, Jinmin Chen, Limin Shi, Qing Liu, Chunfeng Liu, Fuli Zhang & Haoxiang Wu

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  1. Chunmei Zhu
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  2. Jinmin Chen
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  4. Qing Liu
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Contributions

Chunmei Zhu: conceptualization, methodology, investigation, software, writing—original draft preparation. Jinmin Chen: data curation, writing—original draft preparation. Limin Shi: visualization, investigation. Qing Liu: validation. Chunfeng Liu: investigation. Fuli Zhang: writing—review and editing. Haoxiang Wu: conceptualization, methodology, supervision, resources, writing—review and editing.

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Correspondence to Haoxiang Wu.

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Zhu, C., Chen, J., Shi, L. et al. Development of Child-Friendly Lisdexamfetamine Chewable Tablets Using Ion Exchange Resin as a Taste-Masking Carrier Based on the Concept of Quality by Design (QbD). AAPS PharmSciTech 24, 132 (2023). https://doi.org/10.1208/s12249-023-02592-x

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