title: Process analysis of fluidized bed granulation.
abstract: This study assesses the fluidized bed granulation process for the optimization of a model formulation using in-line near-infrared (NIR) spectroscopy for moisture determination. The granulation process was analyzed using an automated granulator and optimization of the verapamil hydrochloride formulation was performed using a mixture design. The NIR setup with a fixed wavelength detector was applied for moisture measurement. Information from other process measurements, temperature difference between process inlet air and granules (T(diff)), and water content of process air (AH), was also analyzed. The application of in-line NIR provided information related to the amount of water throughout the whole granulation process. This information combined with trend charts of T(diff) and AH enabled the analysis of the different process phases. By this means, we can obtain in-line documentation from all the steps of the processing. The choice of the excipient affected the nature of the solid-water interactions; this resulted in varying process times. NIR moisture measurement combined with temperature and humidity measurements provides a tool for the control of water during fluid bed granulation.
authors.affiliation: Viikki Drug Discovery Technology Center, Pharmaceutical Technology Division, University of Helsinki, Finland. jukka.rantanen@helsinki.fi
authors.forename: J
authors.initials: J
authors.lastname: Rantanen
authors.forename: A
authors.initials: A
authors.lastname: Jørgensen
authors.forename: E
authors.initials: E
authors.lastname: Räsänen
authors.forename: P
authors.initials: P
authors.lastname: Luukkonen
authors.forename: S
authors.initials: S
authors.lastname: Airaksinen
authors.forename: J
authors.initials: J
authors.lastname: Raiman
authors.forename: K
authors.initials: K
authors.lastname: Hänninen
authors.forename: O
authors.initials: O
authors.lastname: Antikainen
authors.forename: J
authors.initials: J
authors.lastname: Yliruusi
mesh_terms: D005079:Excipients; D006813:Humidity; D010316:Particle Size; D019265:Spectroscopy, Near-Infrared; D013696:Temperature; D014700:Verapamil / Q000008:administration & dosage / Q000737:chemistry; D014867:Water / Q000032:analysis*
chemical_list: D005079:Excipients; D014867:Water; D014700:Verapamil