(310f) Quality by Design Development of a Film Coating Process Resulting in a Dimensionless Design Space

The Quality by Design development of a film coated tablet drug product began with a risk assessment which identified moisture sensitivity as a key product quality attribute risk.  Additionally, tablet moisture was viewed as a key measure for film coated tablet elegance attributes.  The film coating unit operation, where the drug product was sprayed with an aqueous based coating suspension, was a key focus of this development.  A theory was devised that the tablet moisture could be described by overall thermodynamic factors, spray and tablet flux factors, and geometric factors.  A design of experiments was executed at both lab and commercial film coating scales.  The result of the design of experiments was the identification of the high, medium, and low risk process factors impacting the tablet moisture response via a statistical model in support of this theory.  The design of experiments indicated the scale independence of the moisture response over the range of study.  This allowed the description of the film coating process design space with a collection of dimensionless groups in the product New Drug Application.  This film coating control strategy was accepted by regulatory agencies with the approval of the product and it has been implemented at the commercial site, first with process validation and then with subsequent commercial production.