title: Modeling strategies for pharmaceutical blend monitoring and end-point determination by near-infrared spectroscopy.
abstract: The implementation of a blend monitoring and control method based on a process analytical technology such as near infrared spectroscopy requires the selection and optimization of numerous criteria that will affect the monitoring outputs and expected blend end-point. Using a five component formulation, the present article contrasts the modeling strategies and end-point determination of a traditional quantitative method based on the prediction of the blend parameters employing partial least-squares regression with a qualitative strategy based on principal component analysis and Hotelling's T(2) and residual distance to the model, called Prototype. The possibility to monitor and control blend homogeneity with multivariate curve resolution was also assessed. The implementation of the above methods in the presence of designed experiments (with variation of the amount of active ingredient and excipients) and with normal operating condition samples (nominal concentrations of the active ingredient and excipients) was tested. The impact of criteria used to stop the blends (related to precision and/or accuracy) was assessed. Results demonstrated that while all methods showed similarities in their outputs, some approaches were preferred for decision making. The selectivity of regression based methods was also contrasted with the capacity of qualitative methods to determine the homogeneity of the entire formulation.
authors.affiliation: Duquesne Center for Pharmaceutical Technology, Duquesne University, 600 Forbes Avenue, Pittsburgh, PA 15282, USA.
authors.forename: Benoît
authors.initials: B
authors.lastname: Igne
authors.affiliation: Department of Analytical Chemistry, University of Barcelona, Diagonal 645, Barcelona 08028, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: de Juan
authors.affiliation: IDAEA-CSIC, Jordi Girona 13, Barcelona 08034, Spain.
authors.forename: Joaquim
authors.initials: J
authors.lastname: Jaumot
authors.affiliation: Ondalys, 385 Avenue des Baronnes, Prades-le-Lez 34730, France.
authors.forename: Jordane
authors.initials: J
authors.lastname: Lallemand
authors.affiliation: Ondalys, 385 Avenue des Baronnes, Prades-le-Lez 34730, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Preys
authors.affiliation: Duquesne Center for Pharmaceutical Technology, Duquesne University, 600 Forbes Avenue, Pittsburgh, PA 15282, USA.
authors.forename: James K
authors.initials: JK
authors.lastname: Drennen
authors.affiliation: Duquesne Center for Pharmaceutical Technology, Duquesne University, 600 Forbes Avenue, Pittsburgh, PA 15282, USA. Electronic address: andersonca@duq.edu.
authors.forename: Carl A
authors.initials: CA
authors.lastname: Anderson
mesh_terms: D000082:Acetaminophen / Q000737:chemistry; D002266:Carboxymethylcellulose Sodium / Q000737:chemistry; D002482:Cellulose / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D005079:Excipients / Q000737:chemistry; D007785:Lactose / Q000737:chemistry; D016018:Least-Squares Analysis; D008962:Models, Theoretical; D025341:Principal Component Analysis; D019265:Spectroscopy, Near-Infrared; D013229:Stearic Acids / Q000737:chemistry
chemical_list: D005079:Excipients; D013229:Stearic Acids; D000082:Acetaminophen; C031183:stearic acid; D002482:Cellulose; D007785:Lactose; D002266:Carboxymethylcellulose Sodium; C109691:microcrystalline cellulose
keywords: Chemometrics; End-point detection; Multivariate curve resolution; Near-infrared spectroscopy; Pharmaceutical blend; Prototype