Temperature has rarely been examined in twin-screw wet granulation despite the obvious capabilities of the extruder for operating at elevated temperatures. The present work investigates the wetting behavior of a mixture of powders with different sorption characteristics at various temperatures to explain the unique granulation behavior witnessed with high molecular weight hydroxypropyl methylcellulose in a twin-screw extruder. The work studies the twin-screw granulation of a controlled release formulation at three different temperatures, namely 30 degrees C, 55 degrees C and 80 degrees C and attempts to interpret the granular properties of collected samples relative to characterized moisture sorption isotherms measured for the individual ingredients as well as the mixtures. A result of higher temperature processing was reduced coarse particles and a final product with more spherical granules. Increasing temperature was found to reduce water absorption capacity among the ingredients, especially hydroxypropyl methyl cellulose and microcrystalline cellulose, leaving more of the added water for particle bridging. The gel layer ofhydroxypropyl methyl cellulose particles was diminished by the higher temperatures which did not appear to impact the strength of the particle bridges formed. Inclusion of a more hydrophobic ingredient like acetaminophen complicates the distribution of water in a granule. (C) 2016 Elsevier B.V. All rights reserved.