Drug Delivery · Published 2026-07-22 · DOI 10.1080/10717544.2026.2702143
Thabata Muta, Songhita Mukhopadhyay, Benjamin Noll, Yunmei Song, Sanjay Garg
Cannabidiol (CBD) exhibits poor oral bioavailability (approximately 6%) due to low solubility and excessive first-pass metabolism, limiting its therapeutic potential. This study introduces a novel phospholipid complex self-nanoemulsifying drug delivery system (CBD-PLC-SNEDDS) to enhance CBD delivery. CBD-PLC was integrated into an optimized SNEDDS via Design of Experiments (DoE), yielding nanoemulsions with 118.9 ± 0.77 nm particle size, 0.258 PDI, and −21.9 mV zeta potential. Physicochemical characterization (DSC, FTIR) confirmed amorphization and physical encapsulation without chemical alteration. In vitro dissolution showed 100% CBD release within 1 h for CBD-PLC-SNEDDS vs. 8 h for CBD-SNEDDS. Stability studies (ICH guidelines) retained 94.73% ± 0.62% CBD at 25 °C/60% RH and 80.21% ± 0.61% at 40 °C/75% RH after 4 months with preservatives. In vivo pharmacokinetics in Sprague–Dawley rats (n = 9, 20 mg/kg oral; 4 mg/kg IV) demonstrated that CBD-PLC-SNEDDS significantly enhanced systemic exposure, achieving a calculated absolute bioavailability (F) of 92%, compared to 47% for the oleic acid control. The formulation yielded a 5-fold higher C max (593 ± 246 vs 118 ± 63 ng/mL) doubled AUC0-∞ (88 vs. 45 h·kg·ng/mL/mg), faster T max (2 ± 0.3 vs. 7.4 ± 2.3 h), and extended T 1/2 (3.7 ± 0.9 vs. 1.9 ± 0.6 h) versus control. CBD-PLC alone yielded only 39%. IVIVC modelling via Wagner–Nelson deconvolution established a strong correlation (R2 > 0.7) between in vitro dissolution and in vivo absorption, validating the system's predictive performance. This synergistic PLC-SNEDDS platform outperforms prior systems, offering a scalable template for lipophilic drugs and paving the way for clinical CBD therapeutics.
Abstract from DOAJ. Public domain (CC0 1.0).
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Muta, T., Mukhopadhyay, S., Noll, B., et al. (2026). Development and in vivo pharmacokinetic evaluation of a phospholipid complex self-nanoemulsifying drug delivery system (PLC-SNEDDS) for enhanced oral bioavailability of cannabidiol. Drug Delivery. https://doi.org/10.1080/10717544.2026.2702143