Piperine-pro-nanolipospheres as a novel oral delivery system of cannabinoids: Pharmacokinetic evaluation in healthy volunteers in comparison to buccal spray administration

Cherniakov, Irina; Izgelov, Dvora; Barasch, Dinorah; Davidson, Elyad; Domb, Abraham J.

doi:10.1016/j.jconrel.2017.09.011

Cited by 87 publications

(85 citation statements)

References 20 publications

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“…The average bioavailability of oral capsule was 5.6% (range: 3.4–11.1%), and its variability did not show a significant correlation with feeding status, formulations, or doses. However, it is noted that the bioavailability values of the two fasted‐state oral capsule profiles fall on the lower end of the range . The oral capsule absorption pattern was also well described by the Weibull absorption model.…”

Section: Resultsmentioning

confidence: 88%

“…The absorption kinetics among oral capsule studies were highly variable. The variability may be explained by the various capsule formulations that were included in our study . Feeding status may also contribute to the variability of absorption kinetics among oral capsule studies.…”

Section: Discussionmentioning

confidence: 99%

“…The variability may be explained by the various capsule formulations that were included in our study. 11,13,17,[21][22][23][24] Feeding status may also contribute to the variability of absorption kinetics among oral capsule studies. The presence of food, especially with high-fat content, may slow gastric emptying and gastrointestinal (GI) motility, and therefore delay drug absorption and reduce Cmax.…”

Section: Discussionmentioning

confidence: 99%

“…However, it is noted that the bioavailability values of the two fasted-state oral capsule profiles fall on the lower end of the range. 11,17 The oral capsule absorption pattern was also well described by the Weibull absorption model. A large variability (BSV = 52%) of apparent absorption rate constant, k a , was observed in oral capsule studies, with an average Tmax of 3 hours and a range from 45 minutes to 4 hours.…”

Section: Oral Capsulementioning

confidence: 90%

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Model‐Based Analysis of Cannabidiol Dose‐Exposure Relationship and Bioavailability

2020

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Introduction There is a large variation in cannabidiol (CBD) pharmacokinetics and little information on its bioavailability. This study aims to establish the CBD dose‐exposure relationship and to evaluate the effects of dosage forms, food, and doses on CBD absorption. Methods Single‐dose (range: 5–6000 mg) CBD plasma concentration‐time profiles administered as oral solution (OS), oral capsule (OC), or oromucosal spray/drop (OM) from healthy volunteers were extracted from 15 published clinical studies. A dose‐exposure proportionality assessment was performed, and a population‐based meta‐analysis of CBD pharmacokinetics and systemic bioavailability was conducted with a nonlinear mixed‐effects modeling. A three‐compartment model with a Weibull or zero‐order absorption model was used to describe CBD disposition and absorption kinetics. Dosage form, food, and dose were assessed for covariation. Results Oral solution CBD exposures increased less than proportionally with doses of 750 mg or greater, and bioavailability (6.5% at 3000 mg) decreased with increasing dose. The bioavailability of OC (5.6%) and fed‐state OM (6.2%) were similar, whereas it was lower in fasted‐state OM (0.9%). The Weibull absorption model best described OS, OC, and fed‐state OM profiles. The slowest absorption rate was observed in OS, resulting in a time of maximum concentration of 4.75 hours, followed by fed‐state OM (3.13 hrs) and OC (2.1 hrs). The absorption kinetics of fasted‐state OM was best described by a zero‐order absorption for the duration of 1.71 hours. Conclusion The effects of doses, dosage forms, and feeding status on CBD pharmacokinetics were quantified and should be taken into consideration for dose optimization.

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Section: Resultsmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Oral Capsulementioning

confidence: 90%

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Model‐Based Analysis of Cannabidiol Dose‐Exposure Relationship and Bioavailability

2020

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“…In this context, these substances can take great advantage of nanomedicine-based formulation strategies. Consistently, several studies on nanocarriers encapsulating the different kinds of cannabinoids (phytocannabinoids [12][13][14], cannabidomimetics [15][16][17][18], and endocannabinoids [19]) have started being published with distinct therapeutic purposes. Notwithstanding that for cannabinoids to achieve high translational impact they should be devoid of psychoactive effects, the focus so far has been mainly put on the encapsulation of 9-delta-tetrahydrocannabinol (Δ 9 -THC) and its analogues.…”

Section: Introductionmentioning

confidence: 98%

Lipid nanocapsules decorated and loaded with cannabidiol as targeted prolonged release carriers for glioma therapy: In vitro screening of critical parameters

Aparicio-Blanco

Sebastián

Benoı̂t

et al. 2019

European Journal of Pharmaceutics and Biopharmaceutics

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The therapeutic potential of cannabinoids has been truly constrained heretofore due to their strong psychoactive effects and their high lipophilicity. In this context, precisely due to the lack of psychoactive properties, cannabidiol (CBD), the second major component of Cannabis sativa, arises as the phytocannabinoid with the most auspicious therapeutic potential. Hence, the incorporation of CBD in lipid nanocapsules (LNCs) will contribute to overcome the dosing problems associated with cannabinoids.Herein, we have prepared LNCs decorated and loaded with CBD for glioma therapy and screened in vitro their critical parameters. On the one hand, we have encapsulated CBD into the oily core of LNCs to test their in vitro efficacy as extendedrelease carriers against the human glioblastoma cell line U373MG. The in vitro antitumor effect was highly dependent on the size of LNCs due to its pivotal role in the extent of CBD release. Effectively, a comparison between two differently-sized LNCs (namely, 20-nm and 50-nm sized carriers) showed that the smaller LNCs reduced by 3.0-fold the IC 50 value of their 50-nm sized counterparts. On the other hand, to explore the potential of this phytocannabinoid to target any of the cannabinoid receptors overexpressed in glioma cells, we decorated the LNCs with CBD. This functionalization strategy enhanced the in vitro glioma targeting by 3.4-fold in comparison with their equally-sized undecorated counterparts. Lastly, the combination of CBD-loading with CBD-functionalization further reduced the IC 50 values. Hence, the potential of these two strategies of CBD incorporation into LNCs deserves subsequent in vivo evaluation.

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Food effects on the formulation, dosing, and administration of cannabidiol (CBD) in humans: A systematic review of clinical studies

et al. 2021

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is a non-psychotropic cannabinoid found in the Cannabis plant, as opposed to the psychoactive cannabinoid: tetrahydrocannabinol (THC). 1,2 CBD is found to have a very low oral bioavailability of approximately 9%-13%, which has contributed to major difficulties in drug development. 3 In terms of the timing and importance of this review article, CBD products derived from hemp (Cannabis sativa plants with no parts containing more than 0.3% THC by dry weight) are no longer designated as scheduled products under the 2018 Farm Bill, which removed CBD products from a Schedule I substance designation under the Controlled Substances Act. Further, CBD is the active pharmaceutical ingredient of Epidiolex, which is manufactured by GW Pharmaceuticals and is the first and only Food and Drug Administration (FDA)-approved CBD drug product in the United States. 2 Epidiolex is an oral solution with CBD that is formulated as a 100 mg/ml solution in sesame oil as the primary vehicle with dehydrated alcohol, strawberry flavoring, and sucralose excipients. 2

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Piperine-pro-nanolipospheres as a novel oral delivery system of cannabinoids: Pharmacokinetic evaluation in healthy volunteers in comparison to buccal spray administration

Cited by 87 publications

References 20 publications

Model‐Based Analysis of Cannabidiol Dose‐Exposure Relationship and Bioavailability

Model‐Based Analysis of Cannabidiol Dose‐Exposure Relationship and Bioavailability

Lipid nanocapsules decorated and loaded with cannabidiol as targeted prolonged release carriers for glioma therapy: In vitro screening of critical parameters

Food effects on the formulation, dosing, and administration of cannabidiol (CBD) in humans: A systematic review of clinical studies

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