The ability of different hydrophilic polymers to improve compression behavior of metformin hydrochloride after co-spray drying from aqueous solutions was investigated. Spray dried prodUcts were evaluated by laser diffraction, light microscopy with image analysis, SEM, PXRD, DSC, instrumented press and diametrical loading of compacts. The obtained powders consisted of agglomerated spherical particles with median diameters between 6.7 and 11.0 mu m, and were able to compress after mixing with 7% process aids. Compared with the spray dried drug alone, co-spray drying with polymers resulted in increase of amorphous content (from 0.5 to between 2.0 and 15.6%) associated with increased deformability/interparticle bonding and reduced ejectability. Importance of amorphous content on particle bonding and deformation was confirmed by significant relation between compaction work and relative crystallinity (p = 0.042). Compactability and tabletability Were improved considerably by co-spray drying with the anionic polymers (sodium alginate and sodium carboxymethylcellulose), while decreased by co-spray drying with PVP and copovidone compared to spray dried dtug alone. On the other hand, ejectability was less compromised by co-spray drying with copovidone and HPMC. By using overall desirability scores the polymers were ranked for efficiency in the order: sodium alginate > HPMC > sodium carboxymethylcellulose > copovidone > PVP. The plot of tensile strength vs the ratio [work of compaction/(elastic recovery% x yield pressure)] was a straight line (r = 0.814) allowing prediction of tensile strength from in-die measured parameters. (C) 2016 Elsevier B.V. All rights reserved.