Validation of the pellet coating process used for a new sustained-release theophylline formulation

Within the scope of the validation process described in this report, the influence of the process parameters on the factors determining the quality of Euphylong pellets during the spraying process is examined. The process is challenged within the meaning of the validation guidelines. Investigations within the scope of product-independent validation of the automated fluid bed coating apparatus (Wurster setup) used here provide the basis for installation qualification and operational qualification as defined by the PIC convention and the GMP guidelines. Within the scope of a classification of risks, potential operating and system errors are examined, giving consideration to the worst case conditions, and the relevance of the "blue book" to the process is discussed. Three critical process parameters (spraying temperature, air velocity and relative humidity) are investigated with respect to their influence on the goal parameter "in-vitro release of the active ingredient after 1 h". Product-related validation of the process is accomplished by means of statistical experimental design (factorial design). Statistical analysis is done using the methods described by Box-Wilson and Yates and by response surface research and grid-search methods via contour plots and isometric graphs. This yields the acceptable range of process parameters with respect to product quality. Finally the differences between validation and optimization are discussed.