Exploring supersaturated type IV lipid-based formulations: Impact of supersaturation, digestion and precipitation wInhibition on cinnarizine absorption.

Building up on previous publications for type I, II, IIIa, and IIIb Lipid-based formulations (LBFs), the supersaturation potential for cinnarizine in type IV LBFs and the effect of supersaturation, lipid digestion, and precipitation inhibition in vivo was investigated. The supersaturation potential for cinnarizine-loaded type IV LBFs was high and this was investigated in vivo in rats. Supersaturated LBFs tended to show higher drug exposures in vivo than their non-supersaturated counterparts (22 - 92 % increase in AUC0-24h, not dose-normalized), but this was only statistically significant for the formulation containing a precipitation inhibitor under lipase-inhibited conditions, so the overall impact was limited. Soluplus® as a precipitation inhibitor did not increase drug exposure in general, even though the administered cinnarizine dose was higher for the supersaturated formulations. Lipase inhibition had no impact on cinnarizine absorption, indicating no increased precipitation during digestion. The results were in line with previous findings from type IIIb LBFs that revealed that the digestion process was less important for drug absorption from hydrophilic types of LBFs as opposed to the more lipophilic type I- and II systems.