Krampe Raphael, Sieber Daniel, Pein-Hackelbusch Miriam, Breitkreutz Jörg
Institute of Pharmaceutics and Biopharmaceutics, Heinrich-Heine-University, Universitätsstraße 1, 40225 Düsseldorf, Germany.
Eur J Pharm Biopharm. 2016 Jan;98:20-5. doi: 10.1016/j.ejpb.2015.10.012. Epub 2015 Oct 26.
Specific knowledge about the dissolution behavior under biorelevant conditions is of high interest for the rational development of orodispersible films (ODFs). As the conditions in the oral cavity strongly differ from those in the gastrointestinal tract and from those performed with the pharmacopoeial test setups, a biorelevant dissolution setup was developed in this work, considering the mechanical force of the tongue, the saliva flow, the small fluid volume and the saliva composition. Especially in the initial phase, dissolution profiles of KTP (ketoprofen) ODFs observed by the new method showed a slower drug release than obtained with setups based on conventional dissolution methods. 27.47% KTP release after 100s was detected using the new method, compared to 59.29-82.55% detected without considering the in vivo conditions. Furthermore, an influence of the simulated in vivo conditions on the dissolution profile was observed. By simulating either saliva flow or mechanical force, the KTP release after 100s was two to three times higher (18.78% and 14.18%) compared to the profiles, measured without considering one of the parameters (6.76%). Further studies have to show, whether obtained data are comparable to in vivo data to predict drug release profiles of ODFs in the oral cavity.
对于口腔崩解片（ODF）的合理开发而言，了解其在生物相关条件下的溶出行为具有重要意义。由于口腔环境与胃肠道环境以及药典测试设置中的条件存在显著差异，本研究开发了一种生物相关溶出装置，该装置考虑了舌头的机械力、唾液流动、少量液体体积和唾液成分。特别是在初始阶段，通过新方法观察到的酮洛芬（KTP）口腔崩解片的溶出曲线显示，与基于传统溶出方法的装置相比，药物释放较慢。使用新方法检测到100秒后KTP释放率为27.47%，而未考虑体内条件时检测到的释放率为59.29 - 82.55%。此外，观察到模拟体内条件对溶出曲线有影响。通过模拟唾液流动或机械力，100秒后KTP的释放率比未考虑其中一个参数时测得的曲线（6.76%）高出两到三倍（分别为18.78%和14.18%）。进一步的研究必须表明，所获得的数据是否与体内数据具有可比性，以预测口腔崩解片在口腔中的药物释放曲线。
