Feasibility of developing hospital preparation by semisolid extrusion 3D printing: personalized amlodipine besylate chewable tablets

Abstract

Semisolid extrusion (SSE) 3D printing is an emerging technology in personalized medicine. To address clinical multi-dose requirements, SSE has been explored to manufacture new preparations. In this study, amlodipine besylate (AMB) was the model drug, and SSE was the pharmaceutical strategy. We developed semisolids suitable for SSE and AMB chewable tablets with six strengths (1.5–5 mg) to meet the needs of 2–16-year-old patients. First, the semisolid extrudability was evaluated by texture analyzer, and then the amounts of carboxymethyl cellulose sodium, sodium starch glycolate, and glycerin were optimized by full factorial design. Then, rheological tests were performed to evaluate the properties of the semisolid and the effect of starch sodium glycolate on printability. Finally, the amount of corrigents was optimized using the electronic tongue. Laboratory amplified semisolids and 3D printed tablets can be stored for a few months, and the whole SSE process had no effect on crystal type. This study validated the feasibility of SSE 3D printing, and tablets with appropriate taste and cartoon appearance can meet or even exceed the traditional preparations. Our study provides a new strategy for multi-dose solid preparations and effectively meet the need for personalized amlodipine medicine.

Graphical Abstract

Keywords:

• 3D printing
• semisolid extrusion
• amlodipine besylate
• pediatric hospital preparation
• chewable tablets
• rheological properties

Disclosure statement

The authors declare no conflicts of interest.

Authors contributions

Hui Zhang and Xiang Gao: conceptualization; Xiaolu Han and Hui Zhang: data curation; Dongzhou Kang: formal analysis; Aiping Zheng: funding acquisition; Dongzhou Kang, Boshi Liu, and Zengming Wang: investigation; Xiaolu Han: methodology; Boshi Liu and Xiang Gao: project administration; Aiping Zheng: resources; Xiaolu Han: software; Boshi Liu: supervision; Xiaolu Han: writing – original draft; Zengming Wang, Xiang Gao, and Aiping Zheng: writing – review and editing.

Data availability statement

The appropriate personalized dose of amlodipine was extrapolated from the adult physiologically based pharmacokinetic model. The relevant data are presented in articles published by our team. ‘Optimization of Personalized Amlodipine Dosing Strategies for Children Based on Pharmacokinetic Data from Chinese Male Adults and PBPK Modeling’, https://doi.org/10.3390/children8110950. Due to the different emphasis, it is divided into two articles to elaborate the research content.

Additional information

Funding

This research was funded by the National Natural Science Foundation of China (Grant Number: 82073793) and the Beijing Natural Science Foundation of China. (Grant Number: L202043).