Exploring precipitation inhibitors to improve in vivo absorption of cinnarizine from supersaturated lipid-based drug delivery systems

Supersaturated lipid-based drug delivery systems are increasingly being explored as a bio-enabling formulation approach, particularly in preclinical evaluation of poorlywater-soluble drugs. While increasing the load through thermally-induced supersaturation resulted enhanced vivo exposure for some drugs, others, such cinnarizine, supersaturated have not been found beneficial to increase bioavailability. We hypothesized that incorporation precipitation inhibitors reduce may address this limitation. Therefore, pharmacokinetic profiles cinnarizine with or without were compared. Five selected investigation based on high throughput screening twenty-one excipients. In results showed addition 5% long chain monoglyceride (LCM) medium (MCM) formulations general trend increases bioavailability, albeit only statistically significantly increased Poloxamer 407 + LCM system (i.e. 2.7-fold AUC 0-24h compared inhibitors). It appeared mitigated risk from sLBDDS and overall, bioavailability was comparable previously reported after dosing non-supersaturated lipid systems. summary, drugs which prone systems, inclusion mitigates provides opportunity maximize is ideally suited early efficacy toxicology evaluation.