posted on 2024-01-16, 17:40authored byPankaj Singh Cham, Pankul Kotwal, Kuhu Sharma, Sumit Dhiman, Lakhvinder Singh, Varun Pratap Singh, Ajay Kumar, Utpal Nandi, Parvinder Pal Singh
Cannabidiol (CBD 1)
is a nonpsychotic cannabinoid-based
drug approved by the U.S. FDA for treating refractory epilepsy, namely,
Lennox–Gastaut and Dravet syndrome. However, its low aqueous
solubility and oral bioavailability are compensated by administering
high doses, and there is an increased demand for conjugates with improved
properties. In this direction, the present work is focused on synthesizing
CBD-based prodrugs to address the issue of poor solubility and oral
bioavailability. Several CBD-based prodrugs were synthesized and studied
in a battery of assays: viz, release kinetic (ex vivo), solubility (in vitro), chemical stability (in vitro), plasma stability (ex vivo),
pharmacokinetics (in vivo), and efficacy studies
(in vivo). Among the synthesized prodrugs, the morpholinyl
CBD-based prodrugs 3a and 3aa showed good
release behavior, stability, better solubility, and a plasma profile.
Moreover, prodrug candidate 3aa showed better therapeutic
efficacy. The present study identifies CBD-based prodrugs with improved
physiochemical properties and oral exposure.