(17e) Coating Process Thermodynamics and Its Relevance to the Chemical and Physical Stability of Drug Product

During a film coating process, the processing conditions are typically controlled and monitored ‘macroscopically’ with a lack of information on the actual thermodynamic conditions experienced by the tablets [1]. Such macroscopically measured parameters include the inlet and exhaust air temperature (T) and relative humidity (RH) conditions. An understanding of the T and RH conditions experienced directly by the tablets (microenvironment) may be of utmost importance for drug products that are sensitive to heat and moisture.

PyroButton® data loggers are tablet-sized devices that can record real-time information about the microenvironment experienced by the tablets by including them along with the bulk of the tablets during the coating process [2,3]. In recent studies conducted using PyroButtons®, the authors showed that the tablet-bed microenvironment is more sensitive to process changes as compared to the conventionally-measured variables such as exhaust and inlet air T and RH [3,4]. Additionally, correlations could be established between the measured microenvironment and the coated drug products’ critical quality attributes (CQAs) such as appearance, physical and chemical stability.

The following four case studies will be presented as part of this work discussing drug product CQAs and addressing scale-up:

• Appearance: Logo bridging tablet defect
• Physical stability: Delamination tendency of a bilayer tablet
• Chemical stability: Stability of a moisture-sensitive drug product
• Scale-up: Establishing a process design space and utilization during scale up

It was shown that PyroButton data loggers can be used as an effective PAT tool that can provide a meaningful signature of the coating process that can be correlated to drug product performance. Additionally, these data help to establish a process design space at small-scale and enable successful scale-up trials.

References

1. Pandey P, Bindra DS (2013), Real-time monitoring of thermodynamic microenvironment in a pan coater. J Pharm Sci 102 (2):336-340.
2. Wobker MS, Mehrotra A, Carter B (2010), Use of Commercial Data Loggers to Develop Process Understanding in Pharmaceutical Unit Operations. J Pharm Innov 5 (4):169-180.
3. Pandey P, Ji J, Subramanian G, Gour S, Bindra DS (2014), Understanding the thermodynamic micro-environment inside a pan coater using a data logging device. Drug Dev Ind Pharm 40 (4):542-548.
4. Pandey P, Bindra DS, Felton LA (2014), Influence of process parameters on tablet bed microenvironmental factors during pan coating. AAPS PharmSciTech 15 (2):296-305.