title: The interprocess NIR sampling as an alternative approach to multivariate statistical process control for identifying sources of product-quality variability.
abstract: We are presenting a new approach of identifying sources of variability within a manufacturing process by NIR measurements of samples of intermediate material after each consecutive unit operation (interprocess NIR sampling technique). In addition, we summarize the development of a multivariate statistical process control (MSPC) model for the production of enteric-coated pellet product of the proton-pump inhibitor class. By developing provisional NIR calibration models, the identification of critical process points yields comparable results to the established MSPC modeling procedure. Both approaches are shown to lead to the same conclusion, identifying parameters of extrusion/spheronization and characteristics of lactose that have the greatest influence on the end-product's enteric coating performance. The proposed approach enables quicker and easier identification of variability sources during manufacturing process, especially in cases when historical process data is not straightforwardly available. In the presented case the changes of lactose characteristics are influencing the performance of the extrusion/spheronization process step. The pellet cores produced by using one (considered as less suitable) lactose source were on average larger and more fragile, leading to consequent breakage of the cores during subsequent fluid bed operations. These results were confirmed by additional experimental analyses illuminating the underlying mechanism of fracture of oblong pellets during the pellet coating process leading to compromised film coating.
authors: a Lek Pharmaceuticals, d.d., Sandoz Development Center Slovenia , Ljubljana , Slovenia.
authors: Snežana
authors: S
authors: Marković
authors: a Lek Pharmaceuticals, d.d., Sandoz Development Center Slovenia , Ljubljana , Slovenia.|b Faculty of Pharmacy , University of Ljubljana , Ljubljana , Slovenia.
authors: Janez
authors: J
authors: Kerč
authors: c Lek Pharmaceuticals, d.d., Sandoz Biopharmaceuticals , Mengeš , Slovenia.
authors: Matej
authors: M
authors: Horvat
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods* / Q000592:standards; D004343:Drug Implants / Q000032:analysis* / Q000737:chemistry / Q000592:standards; D065546:Drug Liberation; D007785:Lactose / Q000032:analysis* / Q000737:chemistry / Q000592:standards; D015999:Multivariate Analysis; D011786:Quality Control; D019265:Spectroscopy, Near-Infrared / Q000379:methods* / Q000592:standards
chemical_list: D004343:Drug Implants; D007785:Lactose
keywords: Near-infrared spectroscopy; chemometrics; enteric-coated pellets; manufacturing; multivariate statistical process control