title: Multivariate chemometric approach to fiber-optic dissolution testing.
abstract: The use of fiber optics in in vitro dissolution testing opens up new possibilities for more powerful data evaluation since an entire UV-Vis spectrum can be collected at each measuring point. This paper illustrates a multivariate chemometric approach to the solution of problems of interfering absorbance of excipients in in vitro dissolution testing. Two different chemometric approaches are tested: multivariate calibration using partial least squares (PLS) regression and curve resolution using multivariate curve resolution alternating least squares (MCR-ALS), generalized rank annihilation (GRAM), and parallel factor analysis (PARAFAC). Multivariate calibration (PLS) can, following the construction of a calibration model from a calibration sample set, give selective and accurate determinations of the active ingredient in dissolution testing despite the presence of interfering absorbance from excipients. Curve resolution (MCR-ALS, GRAM, or PARAFAC) can be applied to dissolution testing data in order to determine the dissolution rate profiles and spectra for the interfering excipients as well as for the active ingredient without any precalibration. The concept of the application of these chemometric methods to fiber-optic dissolution testing data is exemplified by analysis of glibenclamide tablets enclosed in hard gelatin capsules. The results show that, despite highly overlapping spectra and unresolved raw data, it is possible with PLS to obtain an accurate dissolution rate profile of glibenclamide. Applying curve resolution makes it possible to obtain accurate estimates of both dissolution rate profiles and spectra of both the gelatin capsule and the glibenclamide. The application of multivariate chemometric methods to fiber-optic dissolution testing brings a fresh scope for a deeper understanding of in vitro dissolution testing, solving the problem of interfering absorbance of excipients and making it possible to obtain dissolution rate profiles and spectra of these. Obtaining dissolution rate profiles of multiple active pharmaceutical ingredients in tablets consisting of several active compounds is another possibility.
authors.affiliation: AstraZeneca R&D Södertälje, Analytical Development, SE-151 85 Södertälje, Sweden. kent.wiberg@astrazeneca.com
authors.forename: Kent H
authors.initials: KH
authors.lastname: Wiberg
authors.forename: Ulla-Karin
authors.initials: UK
authors.lastname: Hultin
mesh_terms: D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D005336:Fiber Optic Technology / Q000379:methods*; D005780:Gelatin; D055100:Optical Fibers
chemical_list: D005780:Gelatin