Avoiding segregation during the loading of a catalyst-inert powder mixture in a packed micro-bed
ABSTRACT The optimal loading protocol of a microreactor (catalyst and inert: 0.1 mm, column: 2 mm internal diameter) with a catalyst-inert mixture is fundamentally different from that of a conventional lab-scale reactor (typical values: catalyst, 2 mm; inert, 0.2 mm; column, 10 mm internal diameter). This is shown to be due to segregation, occurring during loading. The following loading procedure has been used: premix the powders, funnel the mixture down, drop it within the reactor, and densify the bed. The average time a particle takes, from the mixing vial to reach its final position, depends on its properties, which in general results in an axially segregated bed. Radial segregation is observed for particles smaller than 60 mu m, as a result of electrostatic forces. This paper describes for each handling step how to minimise segregation during the loading of a catalyst-diluent solid mixture. This includes using a funnel with a low-friction and steep wall, minimising difference in velocity of particle-gravity flow, and adding more inert after the mixture, prior to the densification step. The term rho(p)d(p)(2) is shown to sufficiently predict segregation due to the velocity difference during gravity flow. Segregation can be observed relatively easily in a glass mock-up reactor. Optimising all the handling steps to minimise segregation results in a visually homogeneous bed. (C) 2009 Elsevier B.V. All rights reserved.
- [Show abstract] [Hide abstract]
ABSTRACT: ecause the majority of active ingredients and excipients in drug products are powders, advances in pharma-ceutical technology will be driven by improving the in-dustry's understanding of granular-material process-ing. In many cases, small amounts of active-drug crystals must be blended with large amounts of excipients with rather dif-ferent physical properties. This leads to many challenges in achieving and maintaining blend uniformity, possibly owing to problems associated with the implemention and scale-up of the blending operation as well as the occurrence of segregation dur-ing transport of the powder mixture (e.g., discharge from the blender). In this study, the authors examined segregation dur-ing sedimentation, or dropping, of a powder through a verti-cal pipe. The resulting sediment was sampled using a collection unit designed to allow a specific property to be profiled as a function of height. For model cohesionless materials and weakly cohesive excipients, marked segregation occurs for drops on the order of a few feet, whereby the mass fraction of the fines is greatest at the top of the sediment. A quantitative framework for understanding such segregation was developed by varying physical and process parameters such as particle-size ratio, pipe diameter, and drop height. The results are consistent with a seg-regation mechanism based on differential particle-gas drag forces. Methods to control segregation during gravity-driven drops of pharmaceuticals are also discussed.445.