Laboratoire de Conception et d´Application de Molécules Bioactives (UMR-7199), Faculté de Pharmacie, UdS-CNRS, 67400 Illkirch-Graffenstaden, France.
Pharmaceutics. 2012 Oct 8;4(4):501-16. doi: 10.3390/pharmaceutics4040501.
One "Quality by Design" approach is the focus on the variability of the properties of the active substance. This is crucially important for active substances that are obtained from natural resources such as herbal plant material and extracts. In this paper, we present various strategies for the development of herbal products especially taking into account the natural batch-to-batch variability (mainly of the dry mass) of tablets that contain a fixed amount of tincture. The following steps in the development have been evaluated for the outcome of the physico-chemical properties of the resulting tablets and intermediates: concentration of the tincture extracted from Echinacea fresh plant, loading of the concentrate onto an inert carrier, the respective wet granulation and drying step, including milling, and the adjuvant excipients for the tablet compression step. The responses that were investigated are the mean particle size of the dried and milled granulates, compaction properties and disintegration time of the tablets. Increased particle size showed a significant increase of the disintegration time and a decrease of the compaction properties. In addition, our results showed that the particle size has a great dependency on the ratio of liquid to carrier during the wet granulation process. Thus, the variability of the respective parameters tested was influenced by the performed strategies, which is how the tincture correlated to its dry mass and the relation of the amount of carrier used. In order to optimize these parameters, a strategy considering the above-mentioned points has to be chosen.
一种“质量源于设计”的方法是关注活性物质性质的可变性。对于从天然资源（如草药植物材料和提取物）中获得的活性物质，这一点至关重要。在本文中，我们提出了各种草药产品的开发策略，特别是考虑到含有固定剂量酊剂的片剂的天然批次间变异性（主要是干重）。已经评估了以下开发步骤对最终片剂和中间体的物理化学性质的结果：从新鲜西洋蓍草植物中提取的酊剂的浓度、将浓缩物加载到惰性载体上、相应的湿法制粒和干燥步骤，包括粉碎，以及片剂压缩步骤中的赋形剂。研究的响应是干燥和粉碎颗粒的平均粒径、片剂的压缩特性和崩解时间。粒径的增加表明崩解时间显著增加，压缩特性降低。此外，我们的结果表明，粒径在湿法制粒过程中对液体与载体的比例有很大的依赖性。因此，所测试的各参数的可变性受到所采用策略的影响，这就是酊剂与其干重的关系以及所用载体量的关系。为了优化这些参数，必须选择一种考虑到上述要点的策略。
