title: Monitoring of multiple solid-state transformations at tablet surfaces using multi-series near-infrared hyperspectral imaging and multivariate curve resolution.
abstract: The assessment of the solid-state stability of active pharmaceutical ingredient (API) and/or excipients in solid dosage forms during manufacturing and storage is mandatory for safeguarding quality of the final products. In this work, the solid-state transformations in tablets prepared as blends of piroxicam monohydrate, polyvinylpyrrolidone and the lactose forms monohydrate or anhydrate were studied when the tablets were exposed to the 23-120 °C range. Multi-series near-infrared hyperspectral images were obtained from the surface of each sample for unveiling the local evolution of the solid-state transformations. The preprocessed spectra from the images (dataset) were arranged in augmented matrices, according to the composition of the tablets, and the profile of the overlapped compounds (relative concentration) along the solid-state transformations in the pixels was resolved by using multivariate curve resolution--alternating least squares (MCR-ALS). Therefore, the dehydration of piroxicam and lactose monohydrates could be mapped separately in the samples (explained variances by the models >96%) even when both compounds were being transformed simultaneously (80-120 °C). The images reproduced the same trends obtained from thermogravimetric analysis of the tablets, with the advantage that the pixel-to-pixel heterogeneity of each compound at the surface of the tablets was highlighted.
authors.affiliation: Institute of Chemistry, State University of Campinas - UNICAMP, P.O. Box 6154, 13084-971 Campinas, SP, Brazil.
authors.forename: Guilherme L
authors.initials: GL
authors.lastname: Alexandrino
authors.affiliation: Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark.
authors.forename: Milad R
authors.initials: MR
authors.lastname: Khorasani
authors.affiliation: Department of Food Science, Faculty of Sciences, University of Copenhagen, Rolighedsvej 30, DK-1958 Frederiksberg C, Denmark.
authors.forename: José M
authors.initials: JM
authors.lastname: Amigo
authors.affiliation: Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark.
authors.forename: Jukka
authors.initials: J
authors.lastname: Rantanen
authors.affiliation: Institute of Chemistry, State University of Campinas - UNICAMP, P.O. Box 6154, 13084-971 Campinas, SP, Brazil. Electronic address: ronei@iqm.unicamp.br.
authors.forename: Ronei J
authors.initials: RJ
authors.lastname: Poppi
mesh_terms: D002626:Chemistry, Pharmaceutical; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry; D007785:Lactose / Q000737:chemistry; D016018:Least-Squares Analysis; D015999:Multivariate Analysis; D010894:Piroxicam / Q000737:chemistry*; D011205:Povidone / Q000737:chemistry; D019265:Spectroscopy, Near-Infrared; D013499:Surface Properties; D013607:Tablets; D013678:Technology, Pharmaceutical / Q000379:methods*; D013696:Temperature; D013818:Thermogravimetry; D014867:Water / Q000737:chemistry
chemical_list: D005079:Excipients; D013607:Tablets; D014867:Water; D010894:Piroxicam; D011205:Povidone; D007785:Lactose
keywords: Dehydration; Lactose; MCR-ALS; Multi-series hyperspectral imaging; Piroxicam; Solid dosage forms