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Application of Quality by Design Principles In the Model Predictions for Scale-up of Tablet Film Coating

Andrew Prpich1, Mary T. Am Ende1, Thomas Katzschner2, Veronica Lubczyk3, Holger Weyhers4, and Georg Bernhard3. (1) Oral Products Center of Emphasis, Pfizer, Eastern Point Road, MS 8156-001, Groton, CT 06340, (2) Site Validation Committee, Pfizer Global Manufacturing, Heinrich Mack Str 35, Illertissen, 89257, Germany, (3) RFT Program Office, Pfizer Global Manufacturing, Heinrich Mack Str 35, Illertissen, 89257, Germany, (4) Site Leadership, Pfizer Global Manufacturing, Heinrich Mack Str 35, Illertissen, 89257, Germany

Two fundamental tablet film coating models were employed through a quality by design (QbD) approach to determine the operating parameters for scale-up of Varenicline IR (Chantix®/Champix®) tablet production in Illertissen, Germany. Due to high product demand, the tablet film coating production capacity was expanded from the existing Glatt GC1250 and IMA Perfima 200 coaters (~115 kg and 160 kg pan load, respectively) to a Glatt GC1500 coater (~350 kg pan load). The models were used in this study to establish an acceptable range of process parameters in the new coater to match the proven acceptable range (PAR) of operating conditions in the existing coaters. The established process parameters were then used to prioritize the experimental design to minimize the number of required trial runs and focus on optimization rather than validation.

A thermodynamic film coating model was used to determine the range of inlet air temperatures required to match the exhaust air conditions across the coaters at the target spray rates (600 – 1000 g/min) and pan air flow rate (6000 m3/hr). A film coating atomization model was used to determine the atomizing air pressure set point to achieve a mean coating solution droplet diameter of approximately 26 microns across the three coaters. Based on the model predictions, the following equipment set points were determined; (1) upper and lower inlet air temperatures of 75°C and 65°C, respectively, to maintain environmental similarity during film coating, and (2) atomization air pressure of 3.0 bar at the 600 g/min spray rate and 3.5 bar at the 1000 g/min spray rate to attain the desired droplet diameter. The recommendations were provided to the commercial site to guide the design of their scale-up trial runs. The results from the actual trials were compared against the corresponding model predictions to assess the validity of the guidance provided based on the two models. The results from this study illustrate how the thermodynamic and atomization film coating models can be used to improve the efficiency of the tablet film coating scale-up process.