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3D DLP 打印布洛芬缓释片的研制及其在大鼠体内的药代动力学评价。

Development of 3D DLP Printed Sustained Release Ibuprofen Tablets and Their Pharmacokinetic Evaluation in Rats.

机构信息

College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, Florida, 32307, USA.

Philadelphia College of Osteopathic Medicine, Philadelphia, Pennsylvania, USA.

出版信息

AAPS PharmSciTech. 2023 Mar 28;24(4):88. doi: 10.1208/s12249-023-02544-5.

Abstract

The objective of the present study was to develop digital light processing (DLP) 3D printed sustained release ibuprofen (IBU) tablets using 3D DLP printers for evaluation in in vitro release and in vivo pharmacokinetic studies with their in vitro-in vivo correlation. The resin formulation and printing parameters were optimized using quality by design (QbD) approach, and IBU tablets were printed using DLP printers which works at 385 and 405 nm wavelengths. Our results demonstrated that formulation consisting of polyethylene glycol diacrylate (PEGDA) 700, water, IBU, and riboflavin printed at 40-s bottom layer exposure time and 30-s exposure time produced tablets using both 385 and 405 nm wavelengths. In vitro dissolution studies showed > 70% drug release at the end of 24 h when printed at 405 nm wavelength with no significant difference between tablets printed at 385 nm. In vivo pharmacokinetic evaluation of the optimized 3D printed tablets printed at 405 nm at oral dose of 30 mg/kg in rats showed sustained release of IBU with significantly (p < 0.05) higher C of 30.12 ± 2.45 µg/mL and AUC of 318.97 ± 16.98 (µg/mL × h) compared to marketed IBU tablet (control). In vivo-in vitro correlation studies showed 80% of drug was absorbed in vivo within 3 h from the pulverized 3D printed tablet, whereas intact 3D tablet showed sustained release of IBU with > 75% IBU release in 24 h in vitro. Overall, IBU tablets fabricated using DLP printing demonstrated sustained release and enhanced systemic absorption with no significant difference in their release profile at different wavelengths.

摘要

本研究的目的是开发数字光处理(DLP)3D 打印的布洛芬(IBU)控释片,用于体外释放和体内药代动力学研究,并进行体外-体内相关性研究。采用质量源于设计(QbD)方法优化树脂配方和打印参数,使用工作波长分别为 385nm 和 405nm 的 DLP 打印机打印 IBU 片。结果表明,由聚乙二醇二丙烯酸酯(PEGDA)700、水、IBU 和核黄素组成的配方,底部层曝光时间为 40s,曝光时间为 30s,使用两种波长(385nm 和 405nm)均可打印出片。体外溶出度研究表明,当使用 405nm 打印时,24 小时后药物释放超过 70%,且在 385nm 打印的片剂之间无显著差异。在大鼠口服 30mg/kg 优化后的 3D 打印片(405nm)的体内药代动力学评价中,IBU 表现出持续释放,C 显著(p<0.05)升高,为 30.12±2.45μg/mL,AUC 为 318.97±16.98(μg/mL×h),与市售 IBU 片(对照)相比。体内-体外相关性研究表明,3D 打印片粉碎后 3 小时内体内吸收 80%的药物,而完整的 3D 片在体外 24 小时内持续释放 IBU,释放超过 75%的 IBU。总之,使用 DLP 打印制造的 IBU 片具有持续释放和增强的系统吸收作用,在不同波长下其释放曲线无显著差异。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/329d/11017792/0e8d3ca6b22a/nihms-1950150-f0001.jpg

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