Using the Absorption Cocktail Approach to Assess Differential Absorption Kinetics of Cannabidiol Administered in Lipid Based Vehicles in Rats.
Lipid-based delivery systems have been vastly investigated as a pharmaceutical method to enhance the oral absorption of lipophilic drugs. However, these vehicles affect not only drug bioavailability, but may also have an impact on gastric emptying, drug disposition, lymphatic absorption and are affected by lipid digestion mechanisms. The work presented here compared pharmacokinetic (PK) behavior of the non-intoxicating cannabinoid cannabidiol (CBD) in sesame oil vs. a self-emulsifying drug delivery system (SNEDDS). This investigation was conducted with a unique tool termed the « absorption cocktail approach ». In this concept, selected molecules: metoprolol, THC and ibuprofen were co-administered with CBD in SNEDDS and sesame oil. This method was used to shed light on the complex absorption process of poorly soluble drugs in-vivo, specifically assessing absorption kinetics of CBD. It was found that the concentration vs. time curve following CBD-sesame oil oral administration showed extended input of the drug with delayed Tmax compared to CBD-SNEDDS. Using the « cocktail » approach, a unique finding was observed when the less lipophilic compounds (metoprolol and ibuprofen) exited the stomach much earlier than the lipophilic cannabinoids in sesame oil, proving differential absorption kinetics. Findings of the absorption cocktail approach reflected the physiological process of the GI e.g gastric retention, stomach content separation, lipid digestion, drug precipitation and more, demonstrating its utility. Nonetheless, the search for more compounds as suitable molecule probes is underway.