Preparation of Multi-particulate Drug Delivery Systems by Fluid Bed Pellet Coating

In comparison to tablets drug loaded pellets exhibit the advantageous properties of multiparticulate drug delivery systems. After administration homogeneous distribution in the gastrointestinal tract takes place, drug is released over a large area avoiding concentration peaks, and bioavailability is improved. Up to this time the number of market products with drug coated inert pellets manufactured with fluid bed technology is limited, and systematic investigations of the process and possible coating amounts fail. Inert microcrystalline cellulose pellets were coated with different amounts of water soluble sodium benzoate (model drug substance) and the excipients polyvinylpyrrolidone (binder) and talcum (anti-sticking agent). The formulation of the coating suspension was kept constant, by prolongation of the spray process time the coating amount was increased from a coating to core ratio of 0.5:1 to 5:1. All trials were carried out twice. A batch laboratory fluid bed apparatus GPCG 1.1 (Glatt GmbH, D-Binzen) with Wurster technique was used. The coating processes were stable and reproducible. Yields were in the range 87-95% without any tendency due to process time. With increasing coating amount particle size rises continuously. The products have a narrow particle size distribution. Sphericity is improved due to homogeneous film formation. The recovery rate of sodium benzoate diminishes with increasing process times due to abrasion at the chamber wall and dust formation. Sodium benzoate is released with very high rate without any influence of polyvinylpyrrolidone and talcum. The weight ratio of coating to core of 3:1 represents the best compromise of high drug loading, sufficient yield and high drug recovery.