Supersaturated silica-lipid hybrids (super-SLH): An improved solid-state lipid-based oral drug delivery system with enhanced drug loading

Abstract

The method of supersaturation for achieving high drug loads in lipid-based formulations is under exploited and relatively unexplored, especially in the case of solid-state lipid-based formulations. Silica-lipid hybrids are solid-state lipid-based formulations designed for improving the oral delivery of poorly water-soluble drugs. However, their application to compounds of low potency and requiring large doses is limited by their low drug loading capacity. Here, an innovative technique to fabricate supersaturated silica-lipid hybrid formulations (super-SLH) has been established and the relationship between drug load and performance investigated. Using the model poorly water-soluble drug, ibuprofen, super-SLH was fabricated possessing drug loads ranging from 8 to 44% w/w, i.e. greater than the previously developed standard ibuprofen silica-lipid hybrids (5.6% w/w). Drug crystallinity of the encapsulated ibuprofen ranged from non-crystalline to part-crystalline with an increase in drug load. Super-SLH achieved improved rates and extents of dissolution when compared to pure ibuprofen, regardless of the drug load. The percentage increase in dissolution extent at 60 min varied from 200 to 600%. The results of the current study indicate that supersaturation greatly improves drug loading and that 16–25% w/w is the optimum loading level which retains optimal dissolution behaviour for the oral delivery of ibuprofen, which has the potential to be translated to other poorly water-soluble drugs.