Windbergs Maike, Strachan Clare J, Kleinebudde Peter
Institute of Pharmaceutics and Biopharmaceutics, Heinrich-Heine-University, Düsseldorf, Germany.
Eur J Pharm Biopharm. 2009 Jan;71(1):80-7. doi: 10.1016/j.ejpb.2008.05.015. Epub 2008 Jun 6.
Three monoacid triglycerides differing in their fatty acid chain lengths were extruded below their melting temperatures. Physical characterization was conducted on the powders as well as the extrudates with a combination of DSC, XRPD and vibrational spectroscopy to get a deeper insight into the complex solid-state behaviour of lipids and solid lipid extrudates during processing and storage. The combination of extrusion temperature and friction was a key factor for the lipid polymorphic behaviour after extrusion. Polymorphic transitions had a strong influence on the dissolution behaviour due to crystallization of the stable beta-form from the unstable alpha-form on the surface of the extrudate. These correlations help to understand the solid-state behaviour of lipids and to avoid process conditions which lead to unstable dosage forms. Tailor-made dissolution profiles for a model drug could be achieved using triglycerides of different fatty acid chain lengths as the dissolution rate is chain-length dependent. The solid-state form of the drug was unchanged after storage in accelerated conditions over 10 months. These studies demonstrate that although triglycerides are a promising basis for oral dosage forms, a good understanding and monitoring of the solid-state behaviour is mandatory to obtain reliable and reproducible dosage forms.
三种脂肪酸链长度不同的单酸甘油酯在其熔点温度以下进行挤出。采用差示扫描量热法（DSC）、X射线粉末衍射法（XRPD）和振动光谱法对粉末以及挤出物进行物理表征，以便更深入地了解脂质和固体脂质挤出物在加工和储存过程中复杂的固态行为。挤出温度和摩擦力的组合是挤出后脂质多晶型行为的关键因素。由于挤出物表面不稳定的α晶型结晶形成稳定的β晶型，多晶型转变对溶解行为有很大影响。这些相关性有助于理解脂质的固态行为，并避免导致剂型不稳定的工艺条件。使用不同脂肪酸链长度的甘油三酯可以实现模型药物的定制溶解曲线，因为溶解速率取决于链长。在加速条件下储存10个月后，药物的固态形式未发生变化。这些研究表明，尽管甘油三酯是口服剂型的一个有前景的基础，但要获得可靠且可重复的剂型，必须对固态行为有良好的理解和监测。
