Pilot clinical and pharmacokinetic study of Δ9-Tetrahydrocannabinol (THC)/Cannabidiol (CBD) nanoparticle oro-buccal spray in patients with advanced cancer experiencing uncontrolled pain.

This pilot study aimed to assess the safety, tolerability, pharmacokinetics and exploratory analgesic effect of a novel water-soluble oro-buccal nanoparticle spray of a cannabis-based medicine (MDCNS-01) in patients with advanced incurable malignancy with unrelieved pain from opioid analgesic. The study was a non-blinded single arm 2 stage study. Stage I was a single escalating dose (n = 5) [2.5 mg Δ9-THC and 2.5 mg CBD) versus a 3-fold escalated dose. Stage II was an up-titrated dose in patients with advanced cancers and intractable pain (n = 25). During Stage I with an increased cannabis-based medicine dose, maximum observed plasma concentrations of cannabinoids were dose dependant. The water-soluble formulation in the current study resulted in a higher median (min, max) systemic exposure of Δ9-THC than CBD (AUC from 2.5 mg each of Δ9-THC and CBD, was 1.71 ng mL.h-1 (1.1, 6.6) and 0.65 ng mL.h-1 (0.49, 4.1), respectively). During stage II a subgroup of patients diagnosed with breast and prostate cancers with bone metastases, had the highest mean pain score improvement from baseline of 40% (unadjusted) and 33% (adjusted for rescue medication use). For all patients the most reported adverse events were mild or moderate drowsiness affecting 11 (44%) and 4 (6%) patients, respectively, and nausea and vomiting that affected 18 (72%) patients. The water-soluble cannabis-based medicine provided acceptable bioavailability for Δ9-THC/CBD, appeared safe and tolerable in advanced incurable cancers with uncontrolled pain with preliminary evidence of analgesic efficacy.

A pilot safety, tolerability and pharmacokinetic study of an oro-buccal administered cannabidiol-dominant anti-inflammatory formulation in healthy individuals: a randomized placebo-controlled single-blinded study.

BACKGROUND: The cannabis plant presents a complex biochemical unit of over 500 constituents of which 70 or more molecules have been classified as cannabinoids binding to cannabinoid receptors. The study aimed to investigate the safety, tolerability, and preliminary pharmacokinetics of a nanoparticle CBD formulation. METHODS: The cannabis-based medicine was elaborated with a micellular technology, to produce a water-soluble nanoparticle CBD-dominant anti-inflammatory cannabis medicine (MDCNB-02). On day one, 12 participants administered 2 sprays and on day 2 administered 6 sprays to alternating right and left cheeks [18 mg of CBD and 0.72 mg of THC]. Four other participants administered 2 and 6 sprays on days 1 and 2, respectively of a nanoparticle placebo. RESULTS: The study met the primary outcomes of safety, tolerability, and preliminary pharmacokinetics of a standardized CBD-dominant anti-inflammatory extract for oro-buccal administration. Bioavailability of a 6 mg and 18 mg dose of CBD (median IQR) was 0.87 and 8.9 ng h mL-1, respectively. The maximum concentration of CBD for the low and high doses administered once per day occurred at 60 min for both concentrations. The median half-life of the 6 mg and 18 mg CBD dose was 1.23 and 5.45 h, respectively. The apparent clearance of CBD was 115 and 34 L min-1 for a 6 mg and 18 mg dose, respectively. CONCLUSION: The oro-buccal nanoparticle formulation achieved plasma concentrations that were largely comparable to other commercial and investigated formulations relative to the concentrations administered. Moreover, there were no reports of adverse effects associated with unfavorable inflammatory sequalae.

The Plasma Bioavailability of Coenzyme Q10 Absorbed from the Gut and the Oral Mucosa.

Coenzyme Q10 (CoQ10) has a central role in the generation of cellular bioenergy and its regulation. The hydrophobicity exhibited by the CoQ10 molecule leads to reports of poor absorption profiles, therefore, the optimization of formulations and modes of delivery is an ever-evolving therapeutic goal. The aim of this study was to investigate different CoQ10 formulations. The article summarizes the findings from an Australian comparative study involving adults administered CoQ10 through different oral delivery platforms. A total of 11 participants (six males and five females) voluntarily participated in a comparative clinical study of three different CoQ10 formulations across a six-week period, completing 198 person-hours of cumulative contribution equivalent to n = 33 participation. All of the eligible participants (n = 11) administered the three formulations blinded from who the commercial supplier of the formulation was and from what the chemical form of the CoQ10 was that was being administered. The dosing between the CoQ10 preparations were dispensed sequentially and were administered following three-week washouts. Three commercial preparations were tested, which included the following: formulations with capsules each containing ubiquinol and ubiquinone (150 mg/capsule), and a liposome ubiquinone formulation (40 mg/mL at 2 actuations of the pump). A significant inter-subject variation in the plasma level of CoQ10 at baseline that was observed to increase with an increase in age. This trend persisted in the post administration of the different formulations. Furthermore, it was observed that the intestinal absorption and bioavailability of CoQ10 varied significantly in the plasma between subjects, irrespective of whether the ubiquinol or ubiquinone forms were administered. The administration of CoQ10 as a liposome for preparation showed the poorest response in bioavailability. Although the ubiquinol capsule form of CoQ10 was observed to have increased in the plasma versus the ubiquinone capsules and the ubiquinol liposome at the two-hour interval, the inter-subject variation was such that the difference was not significant (p > 0.05). All of the CoQ10 formulations showed no further increases in their plasma levels over the remaining study period (i.e., four hours). This study further concluded that the intestinal absorption of CoQ10 is highly variable and is independent of the molecular form administered. Furthermore, it also concludes that liposomes are not an effective vehicle for the oral administration of CoQ10, and as such, did not improve the oral mucosal/sublingual absorption and bioavailability of the molecule. Of interest was the observation that with the increasing subject age, there was an observed increase in the baseline plasma CoQ10 levels in the participants prior to dosing. It was posited that the increase in the baseline plasma levels of CoQ10 with an increase in age could be due to the loss of skeletal muscle mass, a result that still needs to be verified.

Route and Type of Formulation Administered Influences the Absorption and Disposition of Vitamin B12 Levels in Serum.

The administration of biological compounds that optimize health benefits is an ever-evolving therapeutic goal. Pharmaceutical and other adjunctive biological compounds have been administered via many different routes in order to produce a systemic pharmacological effect. The article summarizes the findings from an Australian comparative study in adults administered vitamin B12 through different oral delivery platforms. A total of 16 subjects (9 males, 7 females) voluntarily partook in a comparative clinical study of five different vitamin B12 formulations across a six-month period, completing 474 person-hours of cumulative contribution, that was equivalent to an n = 60 participation. A nanoparticle delivered vitamin B12 through a NanoCelle platform was observed to be significantly (p < 0.05) better absorbed than all other dose equivalent platforms (i.e., tablets, emulsions, or liposomes) from baseline to 1, 3, and 6 h of the study period. The nanoparticle platform delivered vitamin B12 demonstrated an enhanced and significant absorption profile as exemplified by rapid systemic detection (i.e., 1 h from baseline) when administered to the oro-buccal mucosa with no reports of any adverse events of toxicity. The nanoparticle formulation of methylcobalamin (1000 µg/dose in 0.3 mL volume) showed bioequivalence only with a chewable-dissolvable tablet that administered a five times higher dose of methylcobalamin (5000 µg) per tablet. This study has demonstrated that an active metabolite embedded in a functional biomaterial (NanoCelle) may constitute a drug delivery method that can better access the circulatory system.