A Novel Scale Up Model for Prediction of Pharmaceutical Film Coating Process Parameters

Abstract

In the pharmaceutical tablet film coating process, we clarified that a difference in exhaust air relative humidity can be used to detect differences in process parameters values, the relative humidity of exhaust air was different under different atmospheric air humidity conditions even though all setting values of the manufacturing process parameters were the same, and the water content of tablets was correlated with the exhaust air relative humidity. Based on this experimental data, the exhaust air relative humidity index (EHI), which is an empirical equation that includes as functional parameters the pan coater type, heated air flow rate, spray rate of coating suspension, saturated water vapor pressure at heated air temperature, and partial water vapor pressure at atmospheric air pressure, was developed. The predictive values of exhaust relative humidity using EHI were in good correlation with the experimental data (correlation coefficient of 0.966) in all datasets. EHI was verified using the date of seven different drug products of different manufacturing scales. The EHI model will support formulation researchers by enabling them to set film coating process parameters when the batch size or pan coater type changes, and without the time and expense of further extensive testing.Key words pan coater; exhaust air relative humidity index (EHI); scale up; drying ability; atmospheric air; tablet water content In general, pharmaceutical film coatings are applied in order to protect core tablets from light or for masking the taste of the active pharmaceutical ingredients. Therefore, the surface state of the coating layer is important to maintain the expected performance. During the coating process, however, the coating layer surface state is affected by the water content of the tablets. In a conventional approach, the water content of drug products is maintained at the validated level by monitoring the product's temperature and/or the exhaust air temperature during the coating process. In a scale up study, the batch scale and manufacturing equipment are changed according to the progress of the process development stage. At each stage, the water content of drug products is constantly monitored and well-controlled to secure the consistency of the drug product's quality. In this approach, numerous experiments are necessary to optimize the process parameters in each batch scale. As a result, the costs of materials, human resources, and time for development will become considerable.Recently, continuous manufacturing systems, which are based on a no-scale up concept of the drug products, have been proposed and evaluated.1,2) Process analytical technology (PAT) using near infrared spectroscopy (NIR) or Raman spectroscopy has been widely evaluated for the in-line measurement of the water content of tablets, the coated film thickness and other related qualities. [3][4][5][6][7][8] However, in the process controls using spectroscopic analysis, a large amount of experimental data and human resources are required for developing m...

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“…The control system monitors the machine while the automation ensuing batch-to-batch quality compliance and consistency 14 . Modern coaters use computer software designed to make the process more automate and efficient (from charging to discharging) and/or to monitor the number of parameters such as the spin-rate of the drum, coating time 44 , substrate surface flow velocity 17,45 , spray-rate 24 , flow rate and temperature of inlet air 24 , process humidity 46,47 , coating weight gain 42,48 , coating attributes 49,52 and many more 16,23,53,55 . In addition, computerization can store process instructions or recipes that produce specific results 12 .…”