A clinical investigation into the bioavailability of a peroral cannabinoid-Pheroid® formulation
The therapeutic advantages of pure Cannabidiol (CBD), a phytocannabinoid isolated from the Cannabis sativa L. plant, are emphasised by the growing use of CBD in numerous conditions ranging from supplementary to the treatment of severe and debilitating forms of epilepsy. The wide spectrum of therapeutic effects associated with pure CBD is achieved without serious adverse events; providing a rationale for chronic CBD use in these conditions. However, the bioavailability of CBD is limited during oral administration due to the inherently high lipophilic nature of cannabinoids. Pheroid®, an effective and well-established drug delivery system, is known to increase bioavailability of pharmaceutical products. The Pheroid® was formulated to potentially improve the drug properties, with the focus on drug bioavailability. A CBD-pro-Pheroid® drug was developed and optimised. The optimised drug (together with a pro-Pheroid® control) was subjected to 6 months’ accelerated stability testing at conditions 5°C, 25°C/60% RH, 30°C/70% RH and 40°C/75% RH. Characterisation analyses performed included morphology analysis, particle size distribution and zeta potential measurements. The formulation pH, capsule integrity and CBD concentrations were also measured to obtain a comprehensive profile of the CBD-pro-Pheroid® formulation. Preliminary study results confirmed that the optimized CBD-pro-Pheroid® was stable when kept at 25°C/60% RH for 6 months. The stability results also emphasised the need for an established method to formulate and confirm the quality of commercially available and artisanal CBD-preparations. The main objective of the study was to evaluate the bioavailability of the optimised CBD-pro-Pheroid® formulation. This was achieved by conducting a phase 1 clinical trial. The CBD-pro-Pheroid® formulation (containing 20 mg pure pharmaceutical grade CBD and 450 mg pro-Pheroid®) was orally administered as a test formulation and pure CBD was administered as a reference compound to 14 healthy participants. Both male and female participants were included in the randomised cross-over, single-dose and single-centre clinical trial. Following the oral administration of the CBD-pro-Pheroid® consecutive blood samples were collected for 48 hours to obtain a complete pharmacokinetic profile of the formulation. The pharmacokinetic values, including the Area under the curve as a function of bioavailability, and the safety associated with the optimised CBD-pro-Pheroid® were assessed during the trial. Collected blood samples were analysed through the LC-MS/MS bioanalytical method. CBD was detected at the 30 min and 60 min post-administration for the CBD-pro-Pheroid® and the pure CBD products, respectively. A significantly higher mean CBD Cmax of 4.45 ± 3.11 ng/mL was reported for CBD-pro-Pheroid® compared to a mean of 0.18 ± 0.23 ng/mL reported for pure CBD. The AUC0-∞ was documented as 17.09 ng/mL/h and 3.28 ng/mL/h for CBD-pro-Pheroid® and pure CBD, respectively. It was evident from these results that the absorption of the CBD-pro-Pheroid® formulation was significantly higher than the pure CBD, confirming that the pure CBD is ineffective in crossing the biological membranes without an effective vehicle. The CBD bioavailability of the test formulation was favourable when compared to the reference compound and to current literature. Since pure CBD is rarely administered to patients in general practice, a relative bioavailability could not be reported and the extent to which the bioavailability was increased by using Pheroid® remains unconfirmed. The enhanced bioavailability, together with an advantageous safety profile, provides the rationale for the use of pro-Pheroid® as the drug delivery system for CBD and supports the future development of a CBD-pro-Pheroid® formulation.
- Health Sciences