title: Co-extrusion as manufacturing technique for multilayer mini-matrices with dual drug release.
abstract: The aim of this work was to develop by means of co-extrusion a multilayered dosage form characterized by a dual release profile of the same drug. Co-extrudates consisted of two concentric polymer matrices: a core having a lipophilic character and a coat with a hydrophilic character. Diclofenac sodium (DS) was incorporated as model drug in both layers. Several polymers were screened on the basis of their processability via hot melt extrusion (HME) and in vitro drug release. Polymer combinations with suitable properties (i.e., similar extrusion temperature, appropriate drug release profile) were processed via co-extrusion. (Co-) extruded samples were characterized in terms of solid state (XRD, SEM), in vitro drug release, core/coat adhesion, and bioavailability. Based on the polymer screening, two polymer combinations were selected for co-extrusion: ethylcellulose (core) combined with Soluplus® (coat) and polycaprolactone (core) with PEO (coat). These combinations were successfully co-extruded. XRD revealed that DS remained crystalline during extrusion in ethylcellulose, Soluplus®, polycaprolactone, and PEO. The polycaprolactone/PEO combination could be processed at a lower temperature (70 °C), vs. 140 °C for ethylcellulose/Soluplus®. The maximum drug load in core and coat depended on the extrusion temperature and the die dimensions, while adhesion between core and coat was mainly determined by the drug load and by the extrusion temperature. In vitro drug release from the co-extruded formulations was reflected in the in vivo behavior: formulations with a higher DS content in the coat (i.e., faster drug release) resulted in higher Cmax and higher AUC values. Co-extrusion is a viable method to produce in a single step a multilayer dosage form with dual drug release.
authors: Laboratory of Pharmaceutical Technology, Ghent University, Belgium.
authors: L
authors: L
authors: Dierickx
authors: J P
authors: JP
authors: Remon
authors: C
authors: C
authors: Vervaet
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry; D019540:Area Under Curve; D001682:Biological Availability; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004008:Diclofenac / Q000737:chemistry*; D004285:Dogs; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D008297:Male; D008855:Microscopy, Electron, Scanning; D011091:Polyesters / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods*; D013696:Temperature; D014961:X-Ray Diffraction
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004337:Drug Carriers; D011091:Polyesters; D011108:Polymers; D004008:Diclofenac; C016240:polycaprolactone; D011092:Polyethylene Glycols; C013517:ethyl cellulose; D002482:Cellulose
keywords: Dual release; Hot–melt co-extrusion; Multiparticulate dosage form; Polycaprolactone; Polyethylene oxide