title: Investigating the relationship between drug distribution in solid lipid matrices and dissolution behaviour using Raman spectroscopy and mapping.
abstract: In this study, in situ and mapping Raman spectroscopic measurements were used to investigate the physical structure of solid lipid extrudates and relate the structure to dissolution behaviour. Theophylline anhydrate was extruded with tripalmitin, with and without the water-soluble polymer, polyethylene glycol 10000. Raman mapping of the extrudate cores revealed that drug particles of diverse size were dispersed in a continuous lipid phase with or without polyethylene glycol. At the surface, there was evidence of more mixing between the components. Previous characterisation by other methods suggested that the extrudate surface is covered predominantly by lipid, and the Raman mapping suggested that such a layer is in general less than a few micrometres thick. Nevertheless, the lipid layer dramatically reduced the drug dissolution rate. The extrudate cores were also mapped after a period of dissolution testing, and there was no evidence of a uniformly receding drug boundary in the extrudates during drug release. In situ Raman spectroscopy analysis during dissolution testing revealed that the drug distribution in the extrudate affected the formation of theophylline monohydrate. However, the drug release rate was primarily determined directly by drug distribution, with the solid-state behaviour of the drug having a smaller influence.
authors.affiliation: Institute of Pharmaceutics and Biopharmaceutics, Heinrich-Heine-University, Universitaetsstr. 1, 40225 Düsseldorf, Germany.
authors.forename: Maike
authors.initials: M
authors.lastname: Windbergs
authors.forename: Miriam
authors.initials: M
authors.lastname: Haaser
authors.forename: Cushla M
authors.initials: CM
authors.lastname: McGoverin
authors.forename: Keith C
authors.initials: KC
authors.lastname: Gordon
authors.forename: Peter
authors.initials: P
authors.lastname: Kleinebudde
authors.forename: Clare J
authors.initials: CJ
authors.lastname: Strachan
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods; D004337:Drug Carriers / Q000737:chemistry; D008055:Lipids / Q000737:chemistry*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D012995:Solubility; D013059:Spectrum Analysis, Raman / Q000379:methods*; D013499:Surface Properties; D013806:Theophylline / Q000737:chemistry*; D014280:Triglycerides / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D008055:Lipids; D014280:Triglycerides; D011092:Polyethylene Glycols; D013806:Theophylline; C005859:tripalmitin