With the emergence of CBD-based medicines, Sarath Chandar, chief scientific officer, SPI Pharma guides readers through the bioavailability challenges facing this sector of the industry.
CBD
Cannabidiol, or CBD, is one of more than 100 different derivatives of Cannabis. CBD is produced from both synthetic and natural sources. It is non-psychotropic and is being increasingly promoted for its potential therapeutic benefits in pharmaceutical, nutraceutical, cosmetic, food and beverage applications. Companies and consumers are following benefits such as treating pain, nausea, anxiety, schizophrenia, epileptic seizures, and more. There are currently only two pharmaceutical products with clinical data that have been approved by regulatory agencies. There are multiple clinical studies in progress in various phases and for different indications. The number of studies has more than doubled in 2019 over the previous year. Based on some of the early results, an outlook of strong growth is projected for CBD formulations in the pharmaceutical sector.
Market research data indicate global market projections for sales of CBD ranging up to $22B by 2022. While there may not be consensus on the actual size of the market, the one thing researchers seem to agree on is the strong growth rate of up to ~30% per year that is forecast to continue well into the next decade.
Limited clinical data and efficacy issues associated with CBD have resulted in few approved pharma products. GW Pharma’s epilepsy drug, Epidiolex is the only FDA approved product in the US. Despite an explosion of nutraceutical and cosmetic products that have hit the US market in the last two years, none of them have been subjected to the rigorous FDA approval process. Instead, they fall into a regulatory gray area that allows CBD from hemp having less than 0.3% THC to be sold in certain states as consumer products, while being restricted at the federal level.
Regulators are debating the necessary requirements for classification and approval of CBD-based therapies. At the same time, consumers are becoming more discerning and educated, demanding higher quality and consistency in CBD products. Regulations will become more stringent and consumers will demand new products. The debate will likely continue until safety and efficacy claims are proven with clinical studies and reliable finished product testing to determine dosing range. Ultimately, CBD products will require proof of safety, efficacy and appropriate dosing for each indication, in addition to being convenient to transport, store, administer and take.
With this background in mind, it is important to understand CBD from a pharmaceutical perspective. Characterising the solubility, bioabsorption and dosing range are challenges that formulators face when developing new CBD products. CBD is lipophilic and highly susceptible to first pass metabolism, meaning that in its natural state, only about 8 to 12% of the CBD ingested by oral route is capable of being absorbed into the bloodstream and delivering targeted therapeutic benefit.
In addition, CBD made from natural source can result in batch-to-batch variations in composition and concentrations of the active ingredient with different levels of impurities making proper API dosing extremely challenging. Many consumer products on the market today are liquids in oil or tincture form, which inherently carries a higher risk of micro contamination, inaccurate dosing, poor taste, and higher transportation costs. The lack of convenience and cost effectiveness could result in a lack of compliance.
A significant body of work has been conducted in the last 10 years to overcome the challenges of limited oral bioavailability, the variation of CBD from natural sources, and the ability to test accurately for impurities. However, successful pharmaceutical product launches have been few and far between and the current IP landscape presents its own set of challenges in overcoming these obstacles.
Purisys, LLC, a new business spun off from Noramco, and SPI Pharma are working together in a phased approach to tackle these challenges.
Purisys manufactures and supplies controlled substance active pharmaceutical ingredients, produces ultra-pure synthetic CBD that meets the strictest regulatory requirements of health authorities around the world. SPI Pharma manufactures and supplies functional excipient platforms and drug development services, brings significant experience in formulating patient friendly dosage forms, which are particularly useful in 505(b)(2) regulatory pathways. The goal of the collaboration is to generate unique, efficacious CBD dosage forms that deliver improved bioavailability, consistent stability, faster onset of action, lower cost of manufacturing, and that are convenient to carry and take.
So far, the efforts (Phase 1) have focused on the following, which are critical to understanding the basics of formulating with CBD:
- Identifying compatible API-excipient combinations that will provide the functionality required to develop the desired dosage forms without generating unwanted impurities.
- Developing and testing various bioavailability enhancing techniques, some that are established technologies and some novel approaches.
- Establishing a multi-phased formulation strategy based on the outcome from a recent study that examined more than 75 samples of high-purity CBD with various excipients and platforms by stressing the samples and measuring chemical decomposition over time.
Phase 1 is being completed using some of the more commonly published techniques for increasing bioavailability of CBD. Patient-friendly forms like orally dispersible powder and/or tablet prototypes are on schedule to be placed on ICH stability and evaluated for functionality by Q4 2019. These prototypes are expected to deliver therapeutic effects similar to other orally ingested products but in a more convenient delivery format.
Phase 2 work has also begun and focuses on improved bioavailability through multiple, innovative, techniques that will enable lower dosing regimens and administration through more efficacious routes, (e.g. sublingual). If successful, the major benefits of this approach will include reducing the amount of the API (and as a result, the cost), lowering the impact of potential side effects, while delivering faster onset of therapeutic action. The initial results for improved bioavailability have been very encouraging, and the goal is to have proof-of-concept prototypes available by mid-2020.
Phase 3 will focus on getting the formulation into the clinical trial process and will depend on identifying potential licensees for the technology. The work is intended to expand the understanding and utility of CBD by creating innovative formats and enabling the process to make it a more accepted therapy that can make a difference in enhancing patients’ lives.