(586aj) Development of a Robust Film Coating Process: The Impact of Wetting Dynamics On the Film Stress - Film Adhesion Balance

Sun, J., Merck & Co., Inc.
Lu, J., Merck & Co., Inc.
Conway, S. L., Merck & Co., Inc.
Seymour, E., Merck Sharp & Dohme Corp.
Eickhoff, W. M., Merck & Co., Inc.

During development of a tablet film coating process, a film coating defect was observed which obscured tablet debossed markings, rendering the identifying markings to be illegible and resulting in batch failure.  Defect analysis revealed that the defects were associated with film coat bridging across the debossed features.  Literature indicates that this type of coating defect occurs when the internal stresses in the film coat exceed adhesion forces between the film coat and core tablet substrate. It was hypothesized that tension in the film coat was exacerbated during drying when the film coat contracts and is relieved when the coat and pulls away from the core tablet; supporting evidence was obtained.  Characterization studies evaluating the wetting dynamics of the film coat suspension on the core tablet demonstrated that coating droplet extent of spreading and penetration on the core tablet surface was lower than with other formulations which did not exhibit the bridging defect.  Increased film thickness and rate of coating deposition also increased the bridging tendency.  A similar film coating defect in which the film was seen to peel away from the core tablet surface is attributed to the same mechanism as the bridging defect – i.e., film coating internal stresses which are higher than the coating-to-core adhesion forces.  Modifications to the film coating process to balance these stresses were focused on process parameter adjustments to influence drying rate and coating uniformity. Suspension solids concentration was highlighted as an additional process factor which could potentially minimize the risk of tablet appearance failure.  A 23 design of experiments was conducted evaluating film coating process factors.  Regression analysis indicated that the inlet air flow rate was the factor which most strongly influenced the bridging defect, and the ratio of air flow rate to spray rate was the factor which most strongly influenced the peeling defect.  A relatively narrow but robust film coating process design space was demonstrated for this product at both the pilot and commercial scales.