Stabilising disproportionation of lipophilic ionic liquid salts in lipid-based formulations

Lipid based formulations (LBFs) can enhance oral bioavailability, however, their utility may be restricted by low drug loading in the formulation. Converting drugs to drug-ionic liquids (drug-ILs) or lipophilic salts significantly increase lipid solubility but this approach is complicated some cases salt disproportionation, leading a reduction and physical instability. Here we explore stability of weakly basic model drug, cinnarizine (CIN), when paired with decanoate counterion (Dec) form drug-IL, (CIN.Dec). Consistent published studies disproportionation aqueous solution, acidic counterions such as Dec lead generation drug-IL solutions pHs below pHmax. This leads CIN deprotonation less soluble free base precipitation. Subsequent show that these effects reversed acidification formulation (either excess decanoic acid other acids), stimulating pH shift plateau CIN.Dec formation stable CIN.Dec. Altering more conditions, therefore stabilises drug-ILs formed using counterions, viable method promote via inhibition drug-ILs.