Polyglycerol esters of fatty acids as safe and stable matrix forming tableting excipients: A structure-function analysis

Abstract

This work describes a novel approach for the development of extended release matrix tablets with stable performance via direct compaction. Selected molecules belong to polyglycerol esters of fatty acids (PGFAs) - a group of lipid-based excipients (LBE) with advanced solid-state stability - were used for developing extended release tablets. Metformin HCl as a freely water soluble API was used as model substance. Three PGFA compounds with a HLB range of 1.8–4.5 were selected as matrix forming agents. The deformation behavior of tableting blends with and without PGFAs and their flow properties studied. Blends composing PGFAs showed reduced yield pressure and decreased internal friction between particles, suggesting the tendency to plastic behavior of PGFAs and improved flow properties of their blends, respectively. The blends of selected lipids with API and filler were directly processable via direct compression without any pretreatment such as granulation. The resulted tablets showed desired tensile strength and friability. Application of PGFAs with different HLB allowed the tailoring of API release profile for different time periods with the same concentration of lipid in the tablet. The stable release profile was related to the stable solid state of lipids as matrix agent. No in vitro cytotoxic effect was observed by assessing the dehydrogenase activity.