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Int J Pharm ; 657: 124173, 2024 May 25.
Article in English | MEDLINE | ID: mdl-38685441

ABSTRACT

Cannabidiol (CBD) suffers from poor oral bioavailability due to poor aqueous solubility and high metabolism, and is generally administered in liquid lipid vehicles. Solid-state formulations of CBD have been developed, but their ability to increase the oral bioavailability has not yet been proven in vivo. Various approaches are investigated to increase this bioavailability. This study aimed to demonstrate the enhancement of the oral bioavailability of oral solid dosage forms of amorphous CBD and lipid-based CBD formulation compared to crystalline CBD. Six piglets received the three formulations, in a cross-over design. CBD and 7 - COOH - CBD, a secondary metabolite used as an indicator of hepatic degradation, were analyzed in plasma. A 10.9-fold and 6.8-fold increase in oral bioavailability was observed for the amorphous and lipid formulations, respectively. However, the lipid-based formulation allowed reducing the inter-variability when administered to fasted animals. An entero-hepatic cycle was confirmed for amorphous formulations. Finally, this study showed that the expected protective effect of lipids against hepatic degradation of the lipid-based formulation did not occur, since the ratio CBD/metabolite was higher than that of the amorphous one.


Subject(s)
Biological Availability , Cannabidiol , Lipids , Animals , Cannabidiol/pharmacokinetics , Cannabidiol/administration & dosage , Cannabidiol/blood , Cannabidiol/chemistry , Swine , Administration, Oral , Lipids/chemistry , Cross-Over Studies , Liver/metabolism , Drug Compounding , Solubility , Chemistry, Pharmaceutical/methods , Male
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