title: Analysis of matrix dosage forms during dissolution testing using raman microscopy.
abstract: Matrix dosage forms are widely used for sustained drug release. As both the distribution of the matrix components and physical changes during dissolution can impact drug release behavior, a comprehensive investigation of these phenomena is required during matrix development. In this study, Raman microscopy was used to investigate different extrudate formulations in terms of component distribution and structural changes during dissolution testing. Two systems containing the model drug theophylline anhydrate were investigated: a binary system, based on a tripalmitin matrix, and a ternary system, containing tripalmitin and polyethylene glycol. The distribution of the drug and the soluble and insoluble matrix components were mapped during dissolution testing. Although a receding drug boundary was observed, it was not uniformly distant from the matrix edge. The lipid structure remained intact, whereas the water-soluble polymer rapidly dissolved and diffused from the matrix leaving a more extensive network of channels through which the dissolution medium could penetrate and the drug could diffuse. Raman mapping can be considered a useful aid in the direct analysis of multiple matrix components during drug release, and therefore a deeper understanding of factors affecting drug release can be obtained during the development of sustained-release matrices.
authors.affiliation: School of Pharmacy, University of Otago, Dunedin 9054, New Zealand.
authors.forename: Miriam
authors.initials: M
authors.lastname: Haaser
authors.forename: Maike
authors.initials: M
authors.lastname: Windbergs
authors.forename: Cushla M
authors.initials: CM
authors.lastname: McGoverin
authors.forename: Peter
authors.initials: P
authors.lastname: Kleinebudde
authors.forename: Thomas
authors.initials: T
authors.lastname: Rades
authors.forename: Keith C
authors.initials: KC
authors.lastname: Gordon
authors.forename: Clare J
authors.initials: CJ
authors.lastname: Strachan
mesh_terms: D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D007700:Kinetics; D008853:Microscopy; D011092:Polyethylene Glycols / Q000737:chemistry*; D012995:Solubility; D013059:Spectrum Analysis, Raman; D013678:Technology, Pharmaceutical / Q000379:methods*; D013806:Theophylline / Q000737:chemistry*; D014280:Triglycerides / Q000737:chemistry*
chemical_list: D003692:Delayed-Action Preparations; D014280:Triglycerides; D011092:Polyethylene Glycols; D013806:Theophylline; C005859:tripalmitin