The sublingual gland under the tongue allows substances, such as sublingual drops, to be absorbed directly into the bloodstream rather than having to make its way to the small intestine.
Consuming CBD through sublingual tinctures has its benefits. They often taste great and have beneficial effects.
A 2016 study by the European Journal of Pain by Hammell, showed pain from arthritis inflammation was reduced from topical use of CBD on rats.
Sublingual Tinctures Bioavailability
Oromucosal spray is a sublingual method to take in CBD through an oral route. Many patients with multiple sclerosis use THC: CBD Oromucosal sprays to help them manage their pain and perform daily functions and interactions.
Vaping CBD has a different bioavailability than when it is ingested orally. An oral capsule may have better effects than a rectal capsule. Oral bioavailability can be more or less bioavailable than when CBD is taken through intravenous administration.
In fact, a 1986 study published by Biomedical & Environmental Mass Spectrometry reported the bioavailability rate of edibles at 6 percent while other numbers have been 4 to 20 percent, which is quite low.
When it comes to CBD, bioavailability is not a secondary consideration, it is important to the consumer. This is especially true for those taking CBD for medicinal purposes such as pain relief, controlling Alzheimer’s disease symptoms, managing chronic pain, and living with anxiety.
Interest and progress in the concept of cocrystallisation have expanded over recent years and is becoming a well-established process in drug development. Cocrystals consist of the API and one or more unique crystalline co-formers which modify the material properties whilst retaining the intrinsic pharmacological drug activity. Cocrystallisation is a useful method for overcoming problematic properties of drugs by increasing the bioavailability, solubility, dissolution rate, physical form, melting point, tableting, stability, or permeability of drug substances [82,83,84]. Further advantages of crystal preparations include the potential for numerous co-molecules including preservatives, other APIs, and pharmaceutical excipients, as well as providing the opportunity to address intellectual property issues by extending API life cycles and fulfilling patent eligibility criteria .
Solid-state oral delivery allows for 100% of the drug to reach the GI tract and has the potential to improve PK characterisation [76,77]. CBD delivered via this route would also further avoid local side effects associated with use of Sativex oromucosal spray (1:1 CBD:THC) or GI discomfort or pain associated with the vehicle itself in oral liquid formulations . Current investigated solid-dose oral formulations of CBD include a 200 mg CBD tablet by Columbia Care called BeneCeed™, which will be used in a UK clinical trial. Elsewhere, a patent by GW pharmaceuticals lists a solid-state CBD as a potential clinical consideration in the treatment of inflammatory bowel disease . Whilst dosing in this fashion ensures a consistent dose, formulations of this nature do not necessarily address problems associated with poor bioavailability.
In material science, a polymorphism refers to the occurrence of differing crystalline structures of the same chemical compound which can be due to the crystallisation conditions (such as the rate of crystallisation) leading to different molecular conformations . Polymorphic substances have identical chemical composition, thus will demonstrate the same chemical behaviour once in solution. Polymorphism screening is a vital component of pharmaceutical drug development as the existence of polymorphisms can affect drug performance and characteristics; for example, a fourfold difference in solubility can occur between different forms due to differences in dissolution rates . An active pharmaceutical ingredient (API) based on a single polymorphism is likely to have an improved and consistent safety and efficacy profile. These properties may include thermodynamic, kinetic, surface, and mechanical properties, amongst others . Polymorphism is acknowledged as an issue in drug development by key regulatory agencies who have issued guidance on approaches used to control for and to justify using polymorphic forms in drug substances. As stated by the FDA’s guidance document “polymorphism can affect the quality, safety, and efficacy of the drug product”; so controlling polymorphism from the drug substance can provide an easier development with regards to regulatory approval . CBD has been shown to be present as two or more inherent crystalline forms which have potential effects on drug absorption and bioavailability due to different physicochemical properties . To date, no studies have assessed how different crystalline forms may impact the pharmacokinetic profile of CBD, which may have implications for CBD being developed as solid-state forms.
3.2. Solid-State Delivery Formulations
A number of alternative delivery methods by-passing the digestive tract and first pass metabolism are currently under investigation including transdermal and nasal routes, and eye drops, which have been reviewed elsewhere .
In our systematic review, within randomised controlled trials administering CBD (by oral solution, capsules, or oromucosal spray), an average dose of 14 mg/Kg/day was reported in positive outcome trials, compared to 5 mg/Kg/day average dose reported in trials in which CBD did not demonstrate efficacy . The high oral doses that are required for efficacy may impact the occurrence of adverse events (AEs), as well as increasing drug costs to the healthcare provider or patient.
Artelo Biosciences have developed a cocrystal with CBD that was designed to take advantage of cocrystal properties and help alleviate some of the problems with CBD delivery. This cocrystal uses the co-former tetramethylpyrazine (TMP; also called ligustrazine), a plant-derived compound from the Ligusticum species that is widely used in Chinese medicine. TMP may offer increased efficacy and bioavailability, by acting synergistically and changing the physiochemical properties that are associated with ineffective absorption. ART12.11 (CBD:TMP cocrystal) is currently in the nonclinical phase of pharmaceutical development targeted towards post-traumatic stress disorder (PTSD), inflammatory bowel disease (IBD), stroke and rare diseases, and has been recently granted a composition of matter patent in the US.
Kalytera are also exploring inflammatory skin conditions using an L-valine-ester derivative of CBD for topical delivery, which is in pre-clinical stages. Kalytera are also developing a bi-sulphate derivative of CBD for oral delivery which claims to be water soluble, a bi-phosphate CBD derivative aimed for intra-tracheal delivery via a novel aerosolised formulation, and an intravenous (IV) formulation (see Table 1 ). GW Pharmaceuticals list an IV formulation in phase 1 trial for neonatal hypoxic-ischemic encephalopathy (NHIE).