End-Point Prediction of Granule Moisture in a ConsiGmaTM-25 Segmented Fluid Bed Dryer

Abstract

Continuously operated pharmaceutical manufacturing lines often consist of a wet granulation unit operation, followed by a (semi-) continuous dryer. The operating conditions of the dryer are crucial for obtaining a desired final granule moisture. Commercially available dryers lack of a thorough online measurement of granule moisture during the drying process. However, this information could improve the operation of the equipment considerably, yielding a granule moisture close to the desired value (e.g., by drying time and process parameter adjustments in real-time). The paper at hand proposes a process model, which can be parameterized from a very limited number of experiments and then be used as a so-called soft sensor for predicting granule moisture. It utilizes available process measurements for the estimation of the granule moisture. The development of the model as well as parameter identification and validation experiments are provided. The proposed model paves the way for the application of sophisticated observer concepts. Possible future activities on that topic are outlined in the paper.

Continuous twin screw granulation and fluid bed drying: A mechanistic scaling approach focusing optimal tablet properties

“…As shown here and also described in literature, the residual water content is of high impact for further processing of granules and therefore can be also considered as a cMA. Different papers describe model-based approaches to predict and control the residual water content for continuous fluid bed drying processes [31,33,83,93].Within this thesis a simple drying capacity parameter is presented to estimate dryer performance at different equipment scales (see chapter 7.4).…”

Drying in a continuous wet granulation line: Investigation of different end of drying control methods

“…An earlier study focused on the use of NIR techniques to detect final moisture content and the effect of different drying condition on the final moisture [8]. Two studies focused on developing mass balances around the segmented dryer in order to better understand and control the drying process in the dryer [9,10], while a more recent study further developed the model in order to predict the final moisture content [11]. Another recent study focused on the granule breakage phenomena during the drying, reporting a noticeable effect mostly due to the pneumatic transport lines utilised [12].…”

Continuous Pharmaceutical Manufacturing

“…Rehl et al [ 1 ] illustrated how to utilize the modern dynamic process modelling method to create a soft sensor for the moisture content and the end-point prediction of a semi-continuous wet granulation unit operation. In wet granulation, the moisture content in the drying phase is the key critical quality attribute in the decision making of the end-point of the drying phase and the complete wet granulation process.…”