The use of solid-state plasticizers for the hot-melt extrusion of pharmaceutical dosage forms has been shown to be beneficial compared with liquid plasticizers. The purpose of this study was to determine the suitability of citric acid (CA) as a solid plasticizer for the preparation of Eudragit RS PO extended-release matrix systems by a melt extrusion technique. The influence of increasing levels of CA monohydrate (CA MH) or anhydrous CA in the powder blend on the extrusion process parameters (screw speed and motor load) was determined as a function of temperature. The solubility of CA MH in extruded tablets was studied by means of modulated differential scanning calorimetry (MDSC) and powder X-ray diffraction (PXRD). Films were cast from organic solutions to demonstrate the plasticizing effect of CA MH as a change in physico-mechanical properties (tensile strength, elastic modulus and elongation). The CA release from extruded tablets was studied over 12 h. The monohydrate form was found to distinctly facilitate the extrusion of Eudragit RS PO, whereas the addition of anhydrous CA to the polymer powder was less effective. This divergent behaviour in plasticization of Eudragit RS PO was attributed to the higher solubility of the monohydrate in the acrylic polymer. The plasticizing effect of the CA MH reached a plateau at 25% during hot-melt extrusion, which coincided with the solubility limit of the organic acid in the polymer as shown by MDSC and PXRD results. The CA MH increased the flexibility of Eudragit RS PO films, as demonstrated by a decrease in tensile strength and elastic modulus and an increase in elongation as a function of CA MH concentration. The dissolution of CA from the matrix tablets followed an extended-release profile, with CA MH exhibiting a faster dissolution rate than the anhydrous form. In conclusion, CA MH was found to be an effective plasticizer for Eudragit RS PO that facilitates the production of controlled-release matrix systems by hot-melt extrusion.