Although the methodology is not clear from publicly available information, Echo Pharmaceuticals and Ananda Scientific are also investigating formulations which claim to enhance bioavailability and consistency in PK profiles by increasing CBD’s water solubility; Ananda’s Liquid Structure™ Enhanced CBD and Echo Pharmaceutical’s Arvisol, using their lipophilic compound delivery technology Alitra ® . Both compounds are in preclinical or early clinical phase 1 development (see Table 1 ).
A sublingual formulation by Diverse Biotech Inc., and an oral liquid by Emerald Health Pharmaceuticals containing a pure synthetic CBD are both in early clinical phases (see Table 1 ).
Another encapsulated form of CBD is APH-1501 (produced by Aphios), which are time-released capsules in which CBD is encapsulated in biodegradable polymer nanospheres as a lyophilised powder. This CBD is awaiting phase 2 testing in opioid addiction.
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.
Cannabidiol (CBD) has substantial therapeutic potential, but its development as an effective drug by the pharmaceutical industry is hindered by intrinsic characteristics such as low bioavailability, low water solubility, and variable pharmacokinetic profiles. Importantly, lack of patentability of the drug substance also limits the likelihood of an expensive, full development programme in anything other than orphan indications. Potential avenues to overcome these issues with CBD include self-emulsifying drug delivery systems, improved crystal formulations and other solid-state delivery formulations, which are mostly in the pre-clinical or early clinical stages of development. This review identifies issues compromising current delivery of solid-state CBD, and how advanced pharmaceutical development strategies can enable CBD to realise the full potential as a successful therapeutic agent.
3.5. Other Delivery Systems and Formulation in Development
Drug–drug interactions (DDIs) with CBD are a high risk as it is metabolised by, and a competitive inhibitor of, CYP450 enzymes (specifically CYP3A4 and CYP2C19) [39,42]. A case report of a 32-year-old woman with refractory epilepsy receiving tacrolimus (5 mg/day) and CBD (2000–2900 mg/day) reported that after two weeks of co-administration there was a threefold increase in dose-normalised tacrolimus concentrations . A case report of a 37-year-old male similarly suggested CBD can increase warfarin concentrations . More robust evidence of DDIs comes from a meta-analysis assessing four randomised, double-blind, placebo-controlled trials in Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS) (n = 396 LGS, 318 DS) . Authors noted incidences of serious AEs were 8% higher in CBD groups relative to placebo, and in patients taking clobazam alongside CBD, AEs were 14% more common than CBD alone. Blood plasma levels of the pharmacological active metabolite of clobazam, N-desmethylclobazam, were three times higher when administered alongside CBD. Likewise, increases in the CBD metabolite, 7-OH-CBD, are also seen when these drugs are co-administered . Valprorate, another common anti-epileptic drug, is strongly associated with increased liver transaminases levels with CBD use. An FDA report describing clinical data for Epidiolex ® in the treatment of LGS or Dravet syndrome highlighted alanine aminotransferase (ALT) levels were three times the normal limit in 13% of Epidiolex ® treated patients. This AE was also true for patients taking clobazam, but was more common in valproate treated patients. Another study investigating the potential for DDIs with cannabis-based medications using the FDA drug interaction database identified three of the main cytochrome enzymes (CYP3A4, CYP2C9 and CYP2C19) responsible for 20–70% of total cytochrome p450 activity were inhibited by CBD . Furthermore, following oxidative reactions at phase 1 metabolism, CBD is then subject to phase II glucuronidation reactions by the enzymes UGT1A9 UGT2B7 and UGT1A7. Competitive binding for these enzymes between drugs also presents another point at which drug metabolite levels could be altered . These observations indicate the potential for DDIs with CBD in a variety of conditions are likely, and needs to be investigated using large patient studies.
In order to be successfully utilised as a medicine, it is paramount to identify and overcome the inherent challenges that face CBD’s effective delivery, particularly through the oral route, which is the most preferred route for drug delivery by patients and drug developers. Some of the most significant issues with oral CBD include poor bioavailability, variable pharmacokinetics profiles, and possible polymorphisms , which may have unintended consequences of less predictable efficacy, increased side effects and drug–drug interactions with higher doses. This review will outline some of the current issues with CBD pharmaceutics, the novel CBD formulations under development and under clinical investigation, and the strategies to improve CBD delivery and efficacy.
You can join other highly valued customers and see how our implacable service works for yourself by buying CBD oil, capsules, gummies, topicals and flower. We want you to have affordable access to quality CBD products and we work hard every day to achieve that goal. As our customer we strive to offer the best CBD online experience and CBD oil prices that are available in the industry.
We have also provided you a collection of our best sellers and most popular CBD products. If you are ever curious of, where to “buy CBD oil online”, then you have come to the right place. Although, CBD oil is our most popular category, we also offer a variety of amazing CBD creams for sale which is our second most popular category amongst our customers. CBD massage oils and CBD topicals are great for applying to a specific area on your body and work great for our customers. Many of the topical products provide skin hydration and overall healthier skin. Explore our CBD creams for sale and see for yourself. Some of our other popular categories include CBD capsules and CBD gummies and are common for people that want to control the dose and may not particularly enjoy the hemp oil flavor. Our CBD capsules and CBD gummies range between 10mg of CBD to 50mg of CBD. Some of our customers prefer to either take a full dose or even consume only half a gummy to spread out the dosage and effects. The gummies range from zero THC to 0.3% THC so make sure to check the label.
Book My Appointment
CBD Oil for Sale, Get the Best Prices at LeafyQuick
CBD Gummies and CBD Capsules have grown in popularity and can now be seen on a lot of CBD retail and online CBD shops across USA. Many customers prefer CBD Gummies and CBD Capsules and frequently end up searching on google for "CBD Gummies near me". Per conversations with our customers, CBD Gummies and CBD Capsules allow them to monitor the exact dosage each time and these types of CBD products are also more discreet than CBD Oil.