Hot-melt co-extrusion as manufacturing technique for multilayer oral dosage forms

摘要

Co-extrusion implies the simultaneous hot-melt extrusion of two or more materials through the same die, creating a multilayered extrudate. This innovative continuous production technology offers numerous advantages over traditional pharmaceutical processing techniques. Moreover co-extrusion provides great potential for the production of fixed-dose combination products which are gaining importance in pharmaceutical industry. Except from an implant (Implanon®) and a vaginal ring (Nuvaring®), there are no co-extruded dosage forms on the market so far. The aim of this work was to evaluate the potential of hot-melt coextrusion for the production of multilayer (core/coat) oral dosage forms. Possible applications are pointed out and polymers which can be combined in co-extruded dosage forms are selected.In the introduction, the equipment and downstream solutions for processing coextrudates into drug products are reviewed. Requirements and challenges in material selection, considering melt viscosity and multilayer adhesion are pointed out. Examples of medical and pharmaceutical applications are presented and some recent findings considering the production of oral drug delivery systems are summarized. Chapter 1 gives a brief overview of the polymer characteristics relevant for hot-melt co-extrusion (including solubility, hygroscopicity, toxicity, thermal stability, melt viscosity and extrudability). In chapter 2, fixed-dose combination dosage forms are developed by means of hot-melt coextrusion, the core providing sustained drug release and the coat immediate drug release. In chapter 3, hot-melt co-extrusion is assessed for the development of multilayered dosage forms characterized by a dual release profile of the same drug. In chapter 4, fixed-dose combination dosage forms are developed characterized by immediate release for both layers, the layers containing different drugs with different water-solubility. Chapter 5 is a critical evaluation of the co-extrusion process. This chapter questions if hot-melt co-extrusion offers an added value over hot-melt extrusion.