Institute of Pharma Technology, University of Applied Sciences and Arts Northwestern Switzerland, Muttenz, Switzerland.
J Pharm Sci. 2013 Mar;102(3):994-1007. doi: 10.1002/jps.23435. Epub 2012 Dec 29.
Quality by design is an important concept, but only limited research has been invested in concentrated pharmaceutical suspensions. A need exists for novel analytical tools to thoroughly characterize the drug as well as its aggregated particle structure in suspension. This work focuses on lipid-based pharmaceutical suspensions for filling of capsules. A rheological approach, namely the fractal concept of flocculation, is introduced to the pharmaceutical field. The model drug mebeverine hydrochloride was first physicochemically analyzed. A special aim was to study the surface energy profiles using inverse gas chromatography as a critical characteristic for the suspension's rheological behavior. Suspensions were manufactured in laboratory process equipment while applying different homogenization speeds. Flow curves of the final suspensions were measured using a cone-and-plate rheometer. As a result, surface energy profiles revealed differences from one mebeverine lot to another. Different homogenization intensities greatly affected the viscosity and the Mooney model was able to predict experimental values as a function of the drug volume fraction. The fractal concept of flocculation characterized mebeverine in suspension and a slight increase of fractal dimension was noted when homogenization speed was increased. It was concluded that the introduced concepts have large potential for designing quality into concentrated pharmaceutical suspensions.
质量源于设计是一个重要的概念，但目前仅限于对浓缩药物混悬剂的有限研究。需要新型的分析工具来彻底表征药物及其在混悬剂中的聚集颗粒结构。本工作专注于用于填充胶囊的基于脂质的药物混悬剂。流变学方法，即絮凝聚的分形概念，被引入制药领域。模型药物盐酸美贝维林首先进行物理化学分析。特别的目的是使用反气相色谱法研究悬浮液流变行为的表面能分布作为关键特性。混悬剂在实验室工艺设备中制造，同时应用不同的匀浆速度。使用锥板流变仪测量最终混悬剂的流动曲线。结果表明，表面能分布显示出不同美贝维林批次之间的差异。不同的匀浆强度对粘度有很大影响，而莫尼模型能够预测作为药物体积分数函数的实验值。絮凝聚的分形概念对混悬剂中的美贝维林进行了表征，并且当匀浆速度增加时，分形维数略有增加。结论是，所介绍的概念在设计高质量的浓缩药物混悬剂方面具有很大的潜力。
