Orthogonal Redundant Monitoring of a New Continuous Fluid-Bed Dryer for Pharmaceutical Processing by Means of Mass and Energy Balance Calculations and Spectroscopic Techniques

Abstract

In line with the ongoing shift from batch to continuous pharmaceutical production of solid oral dosage forms, a novel continuous fluid-bed dryer was developed. The forced feed nature of the Glatt GPCG2 CM fluid-bed dryer allows continuous, first-in-first-out drying of wet granulate materials based on its compartmentalized, rotating fluidizing chamber. The presented work aims to introduce the dryer's functionalities in detail, and to demonstrate that the rotating fluid-bed chambers facilitates a stable drying behavior, which ensures robust and repeatable residual moisture contents (loss-on-drying [LOD]) of the discharged granules. Furthermore, a mass and energy balance (MEB) is derived, based on the logged process values of the granulating and drying units. Two independent test experiments demonstrate that precise LOD prediction in real time is achievable by MEB to serve as an orthogonal process analytical technology method to common near-infrared spectroscopy. On average, MEB results differed by 0.36% LOD (absolute) from offline reference analyses, and by 0.61% LOD from predictions made with an in-house available near-infrared spectroscopy method. Furthermore, good correlation between the observed and expected thermal energy loss was found. The derived MEB is solely based on physical principles; hence it is product independent and transferable to other materials that are processed on the described equipment.

Keywords: NIR spectroscopy; PAT; continuous fluid-bed drying; continuous manufacturing; glatt GPCG2 CM; mass and energy balance; orthogonal process control; process control.