An investigation into the bioavailability of a peroral cannabinoid-Pheroid® formulation
Grobler, Anne F.
Magwasa, Martin S.
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Cannabidiol (CBD), a phytocannabinoid isolated from the Cannabis sativa plant, has been investigated for its medicinal properties including anti-psychotic, anti- emetic, anti-inflammatory, anxiolytic and anti- convulsant effects1,2. However, the per oral CBD bioavailability has been shown to be only 6%; presumably due to the high lipophilic nature and the extensive first pass metabolism of cannabinoids2,3. The lipid- based Pheroid® drug delivery system is a nano- and micro-sized particle delivery system that has previously been used to increase the bioavailability of pharmaceutical compounds such as certain hormonal, antimicrobial, antimalarial and antituberculosis drugs4,5,6,7.8. Recently, we have demonstrated in an in vivo preclinical study the ability of the Pheroid® to increase the oral bioavailability of CBD in rats compared to existing CBD products. A phase 1 clinical trial to evaluate the oral bioavailability of a Pheroid®-CBD formulation in humans is now underway. (See Table 1.) Preclinical study The bioavailability of four oral CBD formulations and one novel pro-Pheroid® -CBD formulation was compared in nine weeks old healthy Sprague Dawley rats (250 ± 53 g) where n = 8 rats per formulation. Each rat received 20 mg/kg of the relevant CBD product through oral gavage followed by consecutive blood sample collections (200 μL each) for 24 h. The CBD plasma concentration was determined for each sample by LC-MS/MS analysis and used to calculate the pharmacokinetic parameters of each formulation, i.e. Ke, Cmax, Tmax, T1/2 and AUC0–24. Clinical study The bioavailability of a test formulation (CBD-pro- Pheroid®) and a reference compound (CBD alone) will be compared in a singledose, double-blind phase I clinical trial with 12 healthy participants, using a randomized cross-over study design with a three-week wash-out period. Consecutive blood samples will be collected from each participant for 96 h per study arm. LC-MS/MS analysis will be used to determine the CBD plasma concentration in order to calculate the pharmacokinetic parameters, i.e. Ke, Cmax, Tmax, T1/2 and AUC0–96. Results of preclinical study The CBD-pro-Pheroid® formulation yielded a higher CBD C max (157.04 ± 66.58 ng/mL), AUC0–24 (1093.32 ± 470.32 ng/mL.hrs) than most of its comparators without the Pheroid® drug delivery system. Promising in vivo preclinical data showed an increased CBD bioavailability when comparing a novel pro- Pheroid®-CBD formulation to existing CBD formulations and formulations under development. The pharmacokinetic parameters of a similar pro-Pheroid®- CBD formulation in humans will be determined in the current study