Table 3.
Advanced formulations designed in order to penetrate the skin or membranes and to produce systemic effects.
| Route of Absorption | Pharmaceutical Form Type | Disease | Observations | Reference |
|---|---|---|---|---|
| Transdermal | cannabinoids in a gel formulation using Transcutol® | increased penetration through the skin in various disease models | tested in vivo in two rat models of cocaine and alcohol addiction in the prevention of relapse to drug use | [179,180] |
| ZYN001—Synthetic D-glyceryl acid ester prodrug of THC | fibromyalgia and neuropathic pain | tested by Zynerba Pharmaceuticals Inc. (USA), failed to achieve the desired blood levels of THC |
[181] | |
| THC encapsulated in MLVs for transdermal applications. |
pain treatment | tested in vitro for skin penetration by Altum Pharmaceuticals Inc. (USA) |
[182] | |
| gel containing CBD using Transcutol® | epilepsy, developmental and epileptic encephalopathy, fragile-X syndrome, and osteoarthritis |
developed and tested in vitro by Zynerba Pharmaceuticals Inc. (USA) | [183,184] | |
| Transdermal | CBD and argan oil combination using Transcutol® to encapsulate CBD | pain and inflammation associated with rheumatic or arthritic inflammatory disorders | Shemanky et al. [97] reported the beneficial effects of this formulation in a group of ten volunteer patients. | [185] |
| THC prodrugs encapsulated using Transcutol® | patients with pathologically high intraocular pressure |
tested by Zynerba Pharmaceuticals Inc. | [186,187] | |
| Transdermal | stimulus-responsive chitosan/ZnO nanoparticles for transdermal absorption of CBD | epilepsy | delivery system was tested in vitro for drug release properties and cytotoxicity | [188] |
| microemulsion containing THCA and CBDA | increased penetration through the skin in various disease models | tested in vitro for permeation improvement | [189] | |
| CBD emulsions stabilized with chitosan/collagen peptides nanoparticles |
cosmetic applications | in vitro testing demonstrated that particle is able to penetrate the stratum corneum and diffuse into deeper layers of the skin | [190] | |
| Transmucosal (oral) |
oral formulation containing one or more cannabinoid–micelle encapsulation | Alzheimer’s disease, neuropathic pain, Dravet syndrome, Lennox–Gastaut syndrome, myoclonic seizures, juvenile myoclonic epilepsy, refractory epilepsy, schizophrenia, juvenile spasms, tuberous sclerosis complex, West syndrome, anxiety | not tested in vivo | [191] |
| oral formulation containing one or more cannabinoids formulated as encapsulated micelles in the form of mucoadhesive gel, tablet, powder, liquid gel capsule, oral solution, granules, extrudates | tested in vivo on dogs by GW Research Limited (GB) | [192] | ||
| oral formulation comprising a combination of at least two cannabinoids (THC or analogies and CBD or analogues)—in the form of mucoadhesive gel, tablet, powder, liquid gel capsule, oral solution, granules, extrudates | pediatric epilepsy | tested in vivo on dogs by GW Research Limited (GB) | [193] | |
| CBD or another cannabinoid conjugates | cancer | tested by Diverse Biotech Inc. | [194] | |
| TurboCBD™ delivery technology capsules | increasing circulating CBD in various disease | pharmacokinetic profile in a double-blinded, placebo-controlled, cross-over study on 12 healthy volunteers | [195] | |
| Canemes®—solid self-emulsifying pharmaceutical compositions comprising CBD and THC combination |
pain-relieving drug | not tested in vivo | [196,197] | |
| Canemes®—cannabinoids chewing gum containing CBD/ CBDV/ THC/ CBC/ CBG combined with other compounds. | multiple sclerosis-related pain and spasticity, Parkinson’s disease, dementia, restless leg syndrome, and post-herpetic neuralgia |
not tested in vivo | [198] | |
| Transmucosal (oral) |
Canemes®—CBD in the self-emulsifying delivery system | increases bioavailability in various disease | bioavailability tests in human | [199,200] |
| Canemes®—cannabinoid derivatives and conjugates | acute and chronic pain | not tested in vivo | [201] | |
| Canemes®—CBD cyclodextrins; cannabinoids with sulfo-alkyl-β-CD |
pain, Parkinson’s disease | clinical trial | [202,203] | |
| BRCX014—CBD with poloxamer 407, carboxymethyl cellulose, and starch |
various disease | not tested in vivo | [204] | |
| BRCX014—CBD sublingual formulation | cancer treatment | not tested in vivo | [108,205] | |
| BCT-521—Combination of CBD and THC | pain management with cancer patients, Fibromyalgia, symptom relief in patients with advanced cancer |
not tested in vivo | [205] | |
| ZYN001—synthetic D-glyceric acid ester prodrugTHC encapsulations in multilayered lipid vesicles |
fibromyalgia and neuropathic pain pain treatment |
not tested in vivo | [182] | |
| Transmucosal (nasal) |
nasal pharmaceutical product containing CBD plus other cannabinoids for topical application in the nasal cavity | schizophrenia | CBD+THC formulation tested on healthy volunteers | [206] |
| Transmucosal (pulmonary) |
Canemes®—cannabinoid derivatives and conjugates | acute and chronic pain | not tested in vivo | [201] |
| CBD mucoadhesive nanostructured lipid carriers | neuropathic pain | tested in vivo on mice model of neuropathic pain produced a better antinociceptive effect than oral or nasal administration of simple CBD oil | [207] | |
| Canemes®—cannabinoid derivatives and conjugates | acute and chronic pain | not tested in vivo | [201] | |
| Trans-corneal | CBD-loaded mixed polymeric micelles of chitosan | degenerative and inflammatory disease of the eye | tested in vitro on human corneal epithelial cell line | [208] |
| Transmucosal (rectal) |
CBD stable nanosized transfersomes as a rectal colloid | various diseases in which CBD has proven efficacy | tested in vivo for CBD release and nanoparticle delivery through the rectal membrane | [209] |
Abbreviations: MLVs, multi-layered lipid vesicles; THC, tetrahydrocannabinol; CBD, cannabidiol; THCA, tetrahydrocannabinolic acid; CBDA, cannabidiolic acid; CBDV, cannabidivarin; CBC, cannabichromene; CBG, cannabigerol.