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The objective was to investigate a novel application of hot-melt extrusion for the preparation of multiparticulate matrices comprising delayed-release particles. Multiparticulates of different mechanical strengths (theophylline granules, wet-mass extruded/spheronized pellets and drug-layered microcrystalline cellulose spheres) were coated with Eudragit® L30D-55 and characterized regarding potency, moisture content, dissolution properties and tensile strength. The coated particles were incorporated into a water-soluble matrix using hot-melt extrusion. Six hydrophilic polymers including polyethylene glycols, poloxamers and polyethylene oxides were studied as the carrier material for the extrusion. Dissolution testing showed that the maintenance of the delayed-release properties of the incorporated particles was independent of the particle tensile strength, but influenced by the nature of the carrier polymer. High miscibility between the carrier and the coating polymer correlated with increased film permeability and higher drug release in acidic media. Of the materials tested, poloxamer 407 exhibited lower miscibility with the Eudragit® L polymer and matrices containing up to 40% enteric pellets were compliant with the USP dissolution requirements for delayed-release dosage forms. The potential advantages of hot-melt extrusion over direct compression for the processing of soft drug granules coated with Eudragit® L polymer were demonstrated.