title: Effect of experimental design on the prediction performance of calibration models based on near-infrared spectroscopy for pharmaceutical applications.
abstract: Near-infrared spectroscopy (NIRS) is a valuable tool in the pharmaceutical industry, presenting opportunities for online analyses to achieve real-time assessment of intermediates and finished dosage forms. The purpose of this work was to investigate the effect of experimental designs  on prediction performance of quantitative models based on NIRS using a five-component formulation as a model system. The following experimental designs were evaluated: five-level, full factorial (5-L FF); three-level, full factorial (3-L FF); central composite; I-optimal; and D-optimal. The  factors for all designs were acetaminophen content and the ratio of microcrystalline cellulose to lactose monohydrate. Other constituents included croscarmellose sodium and magnesium stearate (content remained constant). Partial least squares-based models were generated using data from individual  experimental designs that related acetaminophen content to spectral data. The effect of each experimental design was evaluated by determining the statistical significance of the difference in bias and standard error of the prediction for that model's prediction performance. The calibration  model derived from the I-optimal design had similar prediction performance as did the model derived from the 5-L FF design, despite containing 16 fewer design points. It also outperformed all other models estimated from designs with similar or fewer numbers of samples. This suggested that  experimental-design selection for calibration-model development is critical, and optimum performance can be achieved with efficient experimental designs (i.e., optimal designs).
authors.affiliation: Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA 15282, USA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Bondi
authors.forename: Benoît
authors.initials: B
authors.lastname: Igne
authors.forename: James K
authors.initials: JK
authors.lastname: Drennen
authors.forename: Carl A
authors.initials: CA
authors.lastname: Anderson
mesh_terms: D000082:Acetaminophen / Q000032:analysis / Q000737:chemistry; D002138:Calibration; D002482:Cellulose / Q000032:analysis / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods* / Q000592:standards*; D007785:Lactose / Q000032:analysis / Q000737:chemistry; D016018:Least-Squares Analysis; D008962:Models, Theoretical; D015999:Multivariate Analysis; D012107:Research Design; D019265:Spectroscopy, Near-Infrared / Q000379:methods* / Q000592:standards*
chemical_list: D000082:Acetaminophen; D002482:Cellulose; D007785:Lactose; C109691:microcrystalline cellulose