Solid dispersions are preferentially formulated as solid dosage forms such as tablets and capsules. The structural stability of the solid dispersions has not been adequately explored during post spray drying manufacturing processes. In this paper, we describe the influence of compression forces on solid dispersions made up of naproxen and PVP-VA 64 prepared by spray drying. Compression of the solid dispersion containing 30% (w/w) of naproxen led to low intensity of the powder X-ray diffraction (PXRD) halo pattern maxima at 2θ = 16.11°, and the uncompressed samples also exhibit higher glass transition broadening than the compressed samples after 21 days storage at 75% RH at ambient temperature which indicates structural changes in the solid dispersion. The intensity of the vibration band at 1654 cm(-1) originating from the interaction between the hydrogen of the carboxylic acid moiety of NAP and the amide carbonyl moiety of PVP-VA 64 was increased for the compressed samples. The consequence of compression was further amplified after a long-term stability study (5 months) where the compressed 40 and 50% (w/w) NAP/PVP-VA 64 solid dispersions showed less crystallinity than the uncompressed samples. This suggests that compression improved the physical stability of the solid dispersions as a result of enhanced drug-polymer interactions.