Digestion is a critical element for absorption of cinnarizine from supersaturated lipid-based type I formulations

Eur J Pharm Sci. 2023 Nov 9:106634. doi: 10.1016/j.ejps.2023.106634. Online ahead of print.ABSTRACTEnabling formulations, such as lipid-based formulations (LBFs), are means to deliver challenging-to-formulate, poorly soluble drugs. LBFs may be composed of lipids, surfactants and/or cosolvents and can be classified depending on the proportions of the components and the hydrophilicity of the surfactant according to the Lipid Formulations Classification System, ranging from type I (very lipophilic) to type IV (hydrophilic). In cases where drug solubility in LBFs does not suffice, e.g. for preclinical toxicity studies, supersaturated LBFs can be used in order to increase the drug load. However, the effect of digestion on drug absorption from supersaturated type I formulations (consisting exclusively of lipids) still remains relatively unexplored and unclear. In the present study, the impact of lipid digestion on absorption of cinnarizine-loaded supersaturated lipid-based formulations of type I was investigated in rats by pre-dosing of the lipase inhibitor orlistat. The lipid chain length and the drug dose were varied by testing medium-chain triglycerides (MCT) and long-chain triglycerides (LCT), both supersaturated and non-supersaturated. Due to the physical instability of supersaturated formulations of cinnarizine, i.e. a potential of precipitation of cinnarizine, the impact of the addition of the amphiphilic polymer Soluplus®, as a potential precipitation inhibitor, was also i...
Source: European Journal of Pharmaceutical Sciences - Category: Drugs & Pharmacology Authors: Source Type: research