Influence of Polymer Film Thickness on Drug Release from Fluidized Bed Coated Pellets and Intended Process and Product Control.

Abstract

Coated drug pellets enjoy widespread use in hard gelatine capsules. In heterogeneous pellets, the drug substance is layered onto core pellets. Coatings are often applied to generate a retarded release or an enteric coating. In the present study, the thickness of a polymer coating layer on drug pellets was correlated to the drug release kinetics. The question should be answered whether it is possible to stop the coating process when a layer thickness referring to an intended drug release is achieved. Inert pellets were first coated with sodium benzoate and second with different amounts of water insoluble polyacrylate in a fluidized bed apparatus equipped with a Wurster inlet. The whole process was controlled in-line and at-line with process analytical technology by the measurement of the particle size and the layer thickness. The in-vitro sodium benzoate release was investigated, and the data were linearized by different standard models and compared with the polyacrylate layer thickness. With increasing polyacrylate layer thickness the release rate diminishes. The superposition of several processes influencing the release results in release profiles corresponding approximately to first order kinetics. The coating layer thickness corresponds to a determined drug release profile. The manufacturing of coated drug pellets with intended drug release is possible by coating process control and layer thickness measurement. Preliminary investigations are necessary for different formulations.