Research paper Process design applied to optimise a directly compressible powder produced via a continuous manufacturing process

Manufacturing of ‘ready-to-compress’ powder mixtures for direct compression was performed by spray drying, without granulation, milling and/or blending steps in between spray drying and compaction. Powder mixtures containing acetaminophen, mannitol, erythritol, maltodextrin, crospovidone, colloidal silicon dioxide and polyoxyethylene 20 sorbitan monooleate were prepared via co-spray drying. A feed suspension having a solid content of 27.2% w/w was selected for further process optimisation because of its high process yield, excellent flowability and short tablet disintegration time. Experimental design was applied to evaluate processibility, physico-chemical properties and compactability of the spray dried powder mixtures. Significant and adequate regression models were developed for powder flowability, median particle size, bulk density, residual moisture content and process yield. An increasing inlet and outlet drying air temperature improved process yield. However, a higher inlet drying air temperature had a negative influence on density and moisture content, while the latter decreased at higher outlet drying air temperatures. Median particle size increased with a higher inlet temperature, while the outlet temperature had the opposite affect. Numerical optimisation determined the optimal spray drying process (inlet temperature: 221 � C, outlet temperature: 81 � C and atomisation pressure: 6 bar) in order to produce ‘ready-to-compress’ powder mixtures. � 2007 Elsevier B.V. All rights reserved.