Co-extruded solid solutions as immediate release fixed-dose combinations.

Abstract The aim of this study was to develop by means of co-extrusion a multilayer fixed-dose combination solid dosage form for oral application characterized by immediate release for both layers, the layers containing different drugs with different water-solubility. In this study polymers were selected which can be combined in a co-extruded dosage form. Several polymers were screened on the basis of their processability via hot-melt extrusion, macroscopic properties, acetylsalicylic acid (ASA) decomposition and in vitro drug release. ASA and fenofibrate (FF) were incorporated as hydrophilic and hydrophobic model drugs, respectively. Based on the polymer screening experiments Kollidon® PF 12 and Kollidon® VA 64 were identified as useful ASA carriers (core), while Soluplus®, Kollidon® VA 64 and Kollidon® 30 were applicable as FF carriers (coat). The combination of Kollidon® 30 (coat) with Kollidon® PF 12 or Kollidon® VA 64 (core) failed in terms of processability via co-extrusion. All other combinations (containing 20% ASA in the core and 20% FF in the coat) were successfully co-extruded (diameter core: 2 mm/thickness coat: 1 mm). All formulations showed good adhesion between core and coat. ASA release from the core was complete within 15–30 min (Kollidon® PF 12) or 30–60 min (Kollidon® VA 64), while FF release was complete within 20–30 min (Kollidon® VA 64) or 60 min (Soluplus®). Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) revealed that both drugs were molecularly dispersed in the carriers. Raman mapping exposed very little intermigration of both drugs at the interface. Fixed-dose combinations with good in vitro performance were successfully developed by means of co-extrusion, both layers providing immediate release.