title: Understanding the solid-state behaviour of triglyceride solid lipid extrudates and its influence on dissolution.
abstract: 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.
authors.affiliation: Institute of Pharmaceutics and Biopharmaceutics, Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: Maike
authors.initials: M
authors.lastname: Windbergs
authors.forename: Clare J
authors.initials: CJ
authors.lastname: Strachan
authors.forename: Peter
authors.initials: P
authors.lastname: Kleinebudde
mesh_terms: D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003460:Crystallization; D004355:Drug Stability; D004356:Drug Storage; D005079:Excipients / Q000737:chemistry*; D044367:Phase Transition; D012995:Solubility; D013055:Spectrophotometry, Infrared / Q000379:methods; D044366:Transition Temperature; D014280:Triglycerides / Q000737:chemistry*; D014961:X-Ray Diffraction
chemical_list: D005079:Excipients; D014280:Triglycerides; C004565:trilaurin; C005859:tripalmitin; C022618:tristearin