Bassetto Rebecca, Amadio Emanuele, Ciampanelli Francesco, Perin Stefano, Ilari Pietro, Gaballo Paolo, Callegari Martina, Feltrin Sara, Gobbo Jacopo, Zanatta Samuele, Bertin Walter
Labomar SpA, Treviso, Italy.
Front Nutr. 2024 May 6;11:1394330. doi: 10.3389/fnut.2024.1394330. eCollection 2024.
This project aims to investigate the release performance of bilayer tablet (BL-Tablet) designed with both fast and slow-release technology, targeting sleep disorders. The tablet incorporates Melatonin, extracts of and . In order to validate the effectiveness of the extended-release profile, an advanced dissolution test was herein proposed. This new method utilizes biorelevant intestinal fluid media and incorporates a stomach-to-intestine fluid changing (SIFC) system. To demonstrate the advantages of employing this method for assessing the controlled release profile of active ingredients, the dissolution results were compared with those obtained using the conventional EU Pharmacopoeia approach. Furthermore, the comparative analysis was extended to include a monolayer tablet version (ML-Tablet) lacking the slow-release technology. Technological characterization and bioaccessibility studies, including intestinal permeability test, were conducted as well to assess the pharmacological performance and bioavailability of active ingredients. The dissolution data recovered revealed that the two dissolution methods did not exhibit any significant differences in the release of ML-Tablet's. However, the dissolution profile of the BL-Tablet exhibited notable differences between the two methods particularly when assessing the behavior of the slow-release layer. In this scenario, both methods initially exhibited a similar release pattern within the first approximately 0.5 h, driven by the fast-release layer of the tablet. Following this, distinct gradual and sustained releases were observed, spanning 2.5 h for the EU Pharmacopoeia method and 8 h for the new SIFC-biorelevant dissolution method, respectively. Overall, the novel method demonstrated a substantial improvement compared to conventional EU Pharmacopoeia test in evaluating the performance of a controlled slow-release technology. Remarkably, the prolonged release technology did not have an adverse impact on melatonin intestinal absorption, and, consequently, maintaining its potential bioavailability of around 78%. Concluding, this research provides valuable insights into how the innovative dissolution test can assist formulators in developing controlled release formulations.
本项目旨在研究采用速释和缓释技术设计的双层片剂（BL-片剂）针对睡眠障碍的释放性能。该片剂含有褪黑素、[具体成分1]提取物和[具体成分2]提取物。为验证缓释特性的有效性，本文提出了一种先进的溶出度测试方法。这种新方法利用生物相关肠液介质，并采用胃到肠液转换（SIFC）系统。为证明采用该方法评估活性成分控释特性的优势，将溶出结果与使用传统欧盟药典方法获得的结果进行了比较。此外，比较分析还扩展到了不含缓释技术的单层片剂版本（ML-片剂）。还进行了包括肠道渗透性测试在内的技术表征和生物可及性研究，以评估活性成分的药理性能和生物利用度。回收的溶出数据显示，两种溶出方法在ML-片剂的释放方面没有表现出任何显著差异。然而，BL-片剂的溶出曲线在两种方法之间表现出显著差异，特别是在评估缓释层的行为时。在这种情况下，两种方法在最初约0.5小时内均呈现相似的释放模式，这是由片剂的速释层驱动的。在此之后，分别观察到明显的逐渐和持续释放，欧盟药典方法持续2.5小时，新的SIFC-生物相关溶出方法持续8小时。总体而言，与传统欧盟药典测试相比，新方法在评估控释缓释技术性能方面有了显著改进。值得注意的是，延长释放技术对褪黑素的肠道吸收没有不利影响，因此，其潜在生物利用度保持在78%左右。总之，本研究为创新溶出度测试如何帮助配方设计师开发控释制剂提供了有价值的见解。
