title: A new criterion to assess distributional homogeneity in hyperspectral images of solid pharmaceutical dosage forms.
abstract: During galenic formulation development, homogeneity of distribution is a critical parameter to check since it may influence activity and safety of the drug. Raman hyperspectral imaging is a technique of choice for assessing the distributional homogeneity of compounds of interest. Indeed, the combination of both spectroscopic and spatial information provides a detailed knowledge of chemical composition and component distribution. Actually, most authors assess homogeneity using parameters of the histogram of intensities (e.g. mean, skewness and kurtosis). However, this approach does not take into account spatial information and loses the main advantage of imaging. To overcome this limitation, we propose a new criterion: Distributional Homogeneity Index (DHI). DHI has been tested on simulated maps and formulation development samples. The distribution maps of the samples were obtained without validated calibration model since different formulations were under investigation. The results obtained showed a linear relationship between content uniformity values and DHI values of distribution maps. Therefore, DHI methodology appears to be a suitable tool for the analysis of homogeneity of distribution maps even without calibration during formulation development.
authors.affiliation: University of Liege (ULg), Department of Pharmacy, CIRM, Laboratory of Analytical Chemistry, CHU, B36, 4000 Liege, Belgium. Electronic address: pysacre@ulg.ac.be.
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Sacré
authors.affiliation: Arlenda S.A., Avenue de l'Hopital, 1, B-4000 Liege, Belgium.
authors.forename: Pierre
authors.initials: P
authors.lastname: Lebrun
authors.affiliation: University of Liege (ULg), Department of Pharmacy, CIRM, Laboratory of Analytical Chemistry, CHU, B36, 4000 Liege, Belgium.
authors.forename: Pierre-François
authors.initials: PF
authors.lastname: Chavez
authors.affiliation: University of Liege (ULg), Department of Pharmacy, CIRM, Laboratory of Analytical Chemistry, CHU, B36, 4000 Liege, Belgium.
authors.forename: Charlotte
authors.initials: C
authors.lastname: De Bleye
authors.affiliation: University of Liege (ULg), Department of Pharmacy, CIRM, Laboratory of Analytical Chemistry, CHU, B36, 4000 Liege, Belgium.
authors.forename: Lauranne
authors.initials: L
authors.lastname: Netchacovitch
authors.affiliation: University of Liege (ULg), Department of Pharmacy, CIRM, Laboratory of Analytical Chemistry, CHU, B36, 4000 Liege, Belgium.
authors.forename: Eric
authors.initials: E
authors.lastname: Rozet
authors.affiliation: Galéphar Research Center M/F, rue du Parc Industriel 39, 6900 Marche-en-Famenne, Belgium.
authors.forename: Régis
authors.initials: R
authors.lastname: Klinkenberg
authors.affiliation: Galéphar Research Center M/F, rue du Parc Industriel 39, 6900 Marche-en-Famenne, Belgium.
authors.forename: Bruno
authors.initials: B
authors.lastname: Streel
authors.affiliation: University of Liege (ULg), Department of Pharmacy, CIRM, Laboratory of Analytical Chemistry, CHU, B36, 4000 Liege, Belgium.
authors.forename: Philippe
authors.initials: P
authors.lastname: Hubert
authors.affiliation: University of Liege (ULg), Department of Pharmacy, CIRM, Laboratory of Analytical Chemistry, CHU, B36, 4000 Liege, Belgium.
authors.forename: Eric
authors.initials: E
authors.lastname: Ziemons
mesh_terms: D002626:Chemistry, Pharmaceutical; D007477:Ions / Q000737:chemistry; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D025341:Principal Component Analysis; D013059:Spectrum Analysis, Raman; D013607:Tablets / Q000737:chemistry*
chemical_list: D007477:Ions; D004364:Pharmaceutical Preparations; D013607:Tablets
keywords: Distributional homogeneity; Hyperspectral imaging; Macropixels; Pharmaceutical formulation; Raman spectroscopy