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

IF 3.4 4区 医学 Q2 PHARMACOLOGY & PHARMACY AAPS PharmSciTech Pub Date : 2023-03-28 DOI:10.1208/s12249-023-02544-5
Keb Mosley-Kellum, Arvind Bagde, Shawn Spencer, Satyanarayan Dev, Mandip Singh
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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 Cmax of 30.12 ± 2.45 µg/mL and AUC(0–24 h) 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.

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3D DLP打印布洛芬缓释片的研制及大鼠药动学评价
本研究的目的是使用3D DLP打印机开发数字光处理(DLP)3D打印布洛芬缓释片,用于评估体外释放和体内药代动力学研究及其体外-体内相关性。使用设计质量法(QbD)优化树脂配方和印刷参数,并使用在385和405nm波长下工作的DLP打印机印刷IBU片剂。我们的研究结果表明,由聚乙二醇二丙烯酸酯(PEGDA)700、水、IBU和核黄素组成的制剂在40秒的底层暴露时间和30秒的暴露时间下印刷,可以使用385和405nm的波长生产片剂。体外溶出度研究表明 >; 当在405nm波长下印刷时,在24小时结束时70%的药物释放,在385nm印刷的片剂之间没有显著差异。优化的3D打印片剂在405nm下以30mg/kg的口服剂量在大鼠体内的体内药代动力学评估显示IBU的持续释放具有显著的(p <; 0.05)更高的Cmax 30.12 ± 2.45µg/mL,AUC(0-24小时)为318.97 ± 16.98(µg/mL × h) 与市售的IBU片剂(对照)相比。体内-体外相关性研究表明,80%的药物在3小时内从粉碎的3D打印片剂体内吸收,而完整的3D片剂显示IBU持续释放 >; 在体外24小时内释放75%的IBU。总体而言,使用DLP印刷制造的IBU片剂表现出持续释放和增强的全身吸收,在不同波长下的释放曲线没有显著差异。
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来源期刊
AAPS PharmSciTech
AAPS PharmSciTech 医学-药学
CiteScore
6.80
自引率
3.00%
发文量
264
审稿时长
2.4 months
期刊介绍: AAPS PharmSciTech is a peer-reviewed, online-only journal committed to serving those pharmaceutical scientists and engineers interested in the research, development, and evaluation of pharmaceutical dosage forms and delivery systems, including drugs derived from biotechnology and the manufacturing science pertaining to the commercialization of such dosage forms. Because of its electronic nature, AAPS PharmSciTech aspires to utilize evolving electronic technology to enable faster and diverse mechanisms of information delivery to its readership. Submission of uninvited expert reviews and research articles are welcomed.
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