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Document Type

Open Access Dissertation

Degree Name

Doctor of Philosophy (PhD)

Degree Program

Chemical Engineering

Year Degree Awarded

2016

Month Degree Awarded

February

First Advisor

Michael A. Henson

Second Advisor

Kostas Saranteas

Third Advisor

T.J. Mountziaris

Fourth Advisor

David P. Schmidt

Subject Categories

Other Chemical Engineering | Thermodynamics | Transport Phenomena

Abstract

Drying of Active Pharmaceutical Ingredients (APIs) is an energy intensive process that is often a manufacturing bottleneck due to its relatively long processing times. A key objective is the ability to determine the drying end point, the time at which all solvent has been evaporated from the solid cake. A novel method for determining the end point of pharmaceutical dryers, based on on-line mass spectrometry is developed and tested. The proposed method offers several advantages over existing spectrometric methods, including the ability to detect when the cake is dry from vapor phase measurements and a very simple implementation that does not require chemometric models. The drying end point was determined as the time at which the gas phase solvent concentration measurement from the mass spectrometer converged to a predicted value computed from a solvent mass balance on the oven assuming zero flow rate from the cake. The method was tested on a laboratory scale vacuum dryer over a range of temperatures and pressures using glass beads with three different particle sizes. The method was validated by performing Loss On Drying (LOD) experiments for one combination of pressure, temperature and bead size.

The mass spectrometer (MS) was used as a Quality by Design (QbD) tool along with thermocouples to understand dynamics in vacuum tray drying. The data indicated that boiling was the dominant mechanism. A multiphase transport model to predict drying performance was developed. It was found that a two phase transport model with the vapor and solid considered as one phase and the liquid treated as the second phase was capable of qualitatively reproducing the drying dynamics. Adjustable model parameters estimated from experimental data collected over a range of operating conditions exhibited trends that provided further insight into drying behavior.
The understanding of drying from a vacuum tray dryer was extended to an Agitated Filter Drier (AFD) using the MS. Further, one of the most challenging issues with the use of an AFD, particle size change, was investigated. The change in particle size of API during drying at different RPMs was studied. The experiments indicated that the process was dominated by breakage of API which showed strong correlation with LOD. Population balance models were used to estimate parameters and derive empirical relations to LOD levels.

Comments

Have made changes mentioned mentioned to me on the 5th of Feruary.

Thank you,

Aditya

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