Institute of Pharmacy and Biochemistry, Therapeutical Life Sciences, Johannes Gutenberg University, Mainz, Germany.
Biopharm Drug Dispos. 2012 Oct;33(7):417-24. doi: 10.1002/bdd.1796. Epub 2012 Jul 11.
Understanding the performance of a drug product in vivo plays a key role in the development of meaningful in vitro drug release methodology. In case of functional chewing gums, the mode and the mechanism of release and the site of application differ significantly from other conventional solid oral dosage forms and require a special consideration to extract meaningful information from clinical studies. In the current study, suitable drug release methodology was developed to predict the in vivo performance of an investigated chewing gum product. Different parameters of the drug release testing apparatus described in the Ph. Eur. and Pharmeuropa were evaluated. Drug release data indicate that the parameters, chewing distance, chewing frequency and twisting motion, affect the drug release. Higher drug release was observed when the frequency was changed from 40 chews/min to 60 chews/min for apparatus A and B, as was the case for the twisting motion when changed from 20º to 40º for apparatus B. As far as the chewing distance is concerned, the release rate was in the following order; apparatus A: 0.3 mm > 0.5 mm > 0.7 mm; apparatus B: 1.4 mm > 1.6 mm > 1.8 mm. A suitable apparatus set-up for in vitro release testing was identified. The method will be useful for the establishment of in vitro in vivo correlations (IVIVC) for medicated chewing gums. Interchangeability of the apparatus for a product is not generally recommended without prior knowledge of the performance of the product, as the construction and principle of operation for the apparatus differ considerably.
理解药物在体内的性能在有意义的体外药物释放方法的开发中起着关键作用。对于功能性咀嚼胶，释放的方式和机制以及应用部位与其他常规的固体口服剂型有很大的不同，需要特别考虑从临床研究中提取有意义的信息。在本研究中，开发了合适的药物释放方法来预测所研究的咀嚼胶产品的体内性能。评估了欧洲药典和 Pharmeuropa 中描述的药物释放测试仪器的不同参数。药物释放数据表明，参数（咀嚼距离、咀嚼频率和扭转运动）会影响药物释放。当仪器 A 和 B 的频率从 40 次/分钟增加到 60 次/分钟时，药物释放量更高，当仪器 B 的扭转运动从 20°增加到 40°时也是如此。就咀嚼距离而言，释放速率的顺序为：仪器 A：0.3mm＞0.5mm＞0.7mm；仪器 B：1.4mm＞1.6mm＞1.8mm。确定了适合体外释放测试的仪器设置。该方法将有助于建立含药咀嚼胶的体外体内相关性（IVIVC）。在没有产品性能预先知识的情况下，不建议一般互换仪器，因为仪器的结构和操作原理有很大的不同。
