Non-Invasive, Continuous, Quantitative Detection of Solvent Content in Vacuum Tray Drying

Abstract

A non-invasive capacitance instrument was embedded in the base of a vacuum-drying tray to monitor continuously the residual amount of solvent left in a pharmaceutical powder. Proof of concept was validated with Microcrystalline Cellulose laced with water, as well as water/acetone mixtures absorbed in a spray-dried Copovidone powder. To illustrate the role of impermeability of the base, we derive a model of vapor sorption that reveals the existence of a kinetic limit when solids are thinly spread, and a diffusion limit with greatly diminished effective diffusivity at large powder thickness. By monitoring the residual solvent content of powders, this new in situ technique offers advantages over indirect methods like mass spectrometry of vapor effluents, but without complications associated with probe fouling. To prescribe design guidelines and interpret signals, we model the electric field shed by the probe when a powder holds variable solvent mass fraction in the vertical direction. Graphical abstract

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