Fluidized and Spouted Bed for the preparation of directly processable amorphous solid dispersions

One of the major challenges for modern formulation development is the increasing number of poorly water-soluble drugs. A common formulation approach to improve the solubility of those poorly soluble active ingredients is to formulate them as amorphous solid dispersions (ASDs) with a suitable polymer candidate.

Hot-melt extrusion (HME) and spray drying (SD) are the most frequently applied techniques for the preparation of ASDs[2]. However, HME is not applicable for thermosensitive substances and a suitable downstream operation is still needed for further processing of the extrusion products. On the other hand, SD results in the formation of fine powder with poor flowability, broad particle size distribution and high sensitivity to electrostatic charge. Therefore, a further compaction step is required to obtain a freely flowable product.

In this study, two new techniques for the preparation of ASDs were assessed. It should be possible to fill the ASD directly into capsules without further processing. Two fluidized bed technologies were investigated. The GF3™ (Figure 1A) is a classic 6-inch Wurster Fluidized Bed (FB) equipment used for drug layering and (functional) coating of starter beads. The API containing liquid is layered on an inert core material in a batch process. In the ProCell5™ technology (Figure 1B) the API containing liquid (solution, suspension, emulsion, melt) is sprayed into the empty process chamber. Initially, fine powder is generated by spray drying, which is continuously agglomerated to seeds, and by further layering, to round pellets.

The process gas enters the process chamber in the ProCellTM not through an inlet air distribution plate, but through slots in the lower part of the equipment, resulting in a spouted bed (SB). Nifedipine (NFD) was used in this study as a model drug. NFD exhibits a very low aqueous solubility and belongs to the BCS class II. Kollidon®-VA64 (KVA64), a vinyl-pyrrolidone-vinyl-acetate-copolymer, was selected as model stabilizing polymer for the ASDs and Cellets®500, microcrystalline cellulose pellets, as inert core material. Click on the image to download the pdf