Overcome barriers to CBD bioavailability with DSM

How is DSM tackling the bioavailability challenge facing CBD-based formulations?


  • Cannabidiol (CBD) is gaining significant interest in the pharmaceutical industry, fueled by mounting scientific evidence demonstrating its potential in a wide variety of therapeutic areas.
  • However, unlocking the full potential of CBD is challenging as the bioavailability of the molecule is low and variable, which creates a significant challenge for formulators and clinicians looking to innovate and provide patients with novel treatment options for their underlying conditions.
  • In this interview, we hear from DSM’s Innovation Manager, Dr. Alexandru Zabara, PhD, on the company’s approach to successfully overcoming the formulation barriers associated with CBD. Read on to discover the outcomes of DSM’s latest research in the field.

Cannabidiol (CBD) is the second most dominant cannabinoid derived from the cannabis sativa plant, after tetrahydrocannabinol (THC). Innovation in the CBD drug development space is gaining worldwide momentum due to increasing scientific data demonstrating the molecule’s promising therapeutic potential in human health. Because of ongoing clinical research, CBD is being considered as a possible treatment in a number of therapy areas, including central nervous system (CNS) diseases1, pain disorders2, cancer3 and more. However, while there is a remarkable opportunity for the development of CBD-based therapies in the aforementioned areas, there are still significant barriers to overcome in relation to the ingredient’s formulation.

CBD has low oral bioavailability, due to the molecule’s lipophilic nature and limited solubility, only 6% of the drug is absorbed into the circulation after oral administration.4 Therefore, to achieve a positive therapeutic outcome, higher doses of the active pharmaceutical ingredient (API) are required – which could bring unwanted problems. DSM is keen to address ways to optimize bioavailability and innovate the market with enhanced CBD-based therapies. As part of this work, DSM has benchmarked formulation technologies against each other to uncover the optimal balance between physico-chemical properties, pharmacokinetic performance and patient compliance. Click on the button below to keep reading our exclusive learnings.

What is the impact of low CBD bioavailability?

Oral drug delivery is the preferred administration route for many patients as it is the easiest and most convenient way to deliver pharmaceuticals. However, oral delivery is not always the easiest route for manufacturers, especially when it comes to molecules with low bioavailability – like CBD. Dr. Zabara comments: “Our research investigating ways to increase the compliance of CBD-based therapies was started with the patient front of mind. At present, many of those patients using CBD have to administer large volumes of liquid formulations to achieve a positive therapeutic outcome. We want to change this by creating a solid dosage form with significantly higher drug loading and a superior pharmacokinetic performance, leading to a more patient-friendly therapy without compromising on effectiveness. That’s why we are developing a customized technology platform that will give companies the opportunity to enter the CBD space with superior IP-protected formulations equipped with a high API loading, great physical and chemical stability and of course enhanced oral bioavailability.”

How is DSM addressing CBD bioavailability?

DSM’s team of scientists are exploring a number of drug delivery technologies to address CBD’s low bioavailability. Dr. Zabara comments on the research so far: “To improve CBD’s formulation, we considered both elements that contribute to the reported low absolute bioavailability of the API – incomplete absorption in the gut and extensive hepatic metabolism in the liver.5 To this end we strived to increase the amount of CBD that is absorbed through the intestinal wall while also exploring excipients that favor an alternative metabolic pathway”.

Dr Zabara continues: “Next, we assessed the effectiveness of multiple technologies previously demonstrated to enhance the bioavailability of other poorly soluble drugs. These include nano-emulsification, formation of amorphous solid dispersions, liposomal and lipid nanoparticle formulation. To identify which formulation approach was the most suitable for CBD (and other cannabinoids), we decided to test and benchmark them against each other. As part of our investigation, we’re using a combination of physical characterization techniques, in-vitro bioaccessibility testing and animal models to correlate the physical properties and compositional uniqueness of differently formulated CBD API against their bioaccessibility profile and pharmacokinetic performance. Preliminary results are promising. Our team has already demonstrated a link between the bioaccessibility of CBD and the physical state and stability of the API in solution and its in-vivo performance in an animal model.”

What does this research mean for companies bringing new CBD therapies to market?

Dr. Zabara remarks: “Generating CBD-based therapies with superior pharmacokinetics will help companies overcome the challenges associated with specific market authorization pathways that limit the daily dosage of CBD API. What’s more, improving CBD’s bioavailability will increase the amount of molecule that enters the circulation, enhancing its efficacy and increasing the probability of success in clinical trials. Significantly increasing the API loading without compromising on physical and chemical stability can also result in more patient-centric and cost-efficient finished drugs as lower overall dosages would be required. With that being said, our research is making a wider array of finished drug formats available in a market currently dominated by liquid applications, such as oils and soft gel capsules. Moreover, the technologies we are developing to overcome the challenges associated with formulating cannabinoids could benefit companies looking to overcome similar challenges in the minor cannabinoid space.”

Future developments in the pipeline

Commenting on the ongoing investigation, Dr. Zabara says: “Our in-vivo pre-clinical research has already delivered promising results as we have identified delivery technologies that are superior to the current leading liquid format. Our continued work will inform us on which excipients and formulation technologies to take forward as viable candidates for clinical affirmation and eventual product development. Not only are we helping to improve the bioavailability of such a promising therapeutic molecule, but we’re also helping to educate the pharma industry about which formulations perform best for their intended specific applications. Our work is powering innovation in the rapidly evolving CBD space, and we’re excited to help customers realize the full potential of this molecule.”

Dr. Zabara continues: “We only need to look at the number of people that CBD therapies have helped in the past years to appreciate that this molecule is changing the future for Pharma. For example, people struggling with drug resistant epilepsy now have access to a treatment that can restore their quality of life and reduce both the intensity and occurrence of their seizures. Moreover, people struggling with neuropathic pain, spasticity and other symptoms associated with multiple sclerosis now have access to an oromucosal spray that can alleviate their symptoms. In my opinionthese examples are just the tip of the iceberg and with growing pre-clinical and clinical research, as well as innovation activities in CBD formulation, the coming years will open the cannabinoid and minor cannabinoid therapeutic space and unlock the full potential of these molecules.”

CBD innovation powered by DSM

Through its exclusive and strategic partnership with cannabinoid pioneer, Brains Bioceutical, DSM is helping innovators realize the therapeutic potential of CBD. DSM has created an innovation platform to unlock bespoke cannabinoid-based pharmaceuticals and expand treatment options for patients worldwide. Together, DSM and Brains Bioceutical offer a unique end-to-end service including a high quality, THC-free CBD API, customized solutions, including formulation and technical capabilities that have been shown to improve the bioavailability of CBD, as well as regulatory, quality and scientific expertise for early-stage drug development.


Learn more about the untapped potential of CBD here.


1. Ożarowski, M., Karpiński, T. M., Zielińska, A., Souto, E. B., & Wielgus, K. Cannabidiol in Neurological and Neoplastic Diseases: Latest Developments on the Molecular Mechanism of Action. International journal of molecular sciences22(9), 4294 (2021).

2. Argueta, D. A., Ventura, C. M., Kiven, S., Sagi, V., & Gupta, K. A Balanced Approach for Cannabidiol Use in Chronic Pain. Frontiers in pharmacology11, 561 (2020).

3. O'Brien K. Cannabidiol (CBD) in Cancer Management. Cancers14(4), 885 (2022).

4. Perucca & Bialer. Critical aspects affecting cannabidiol oral bioavailability and metabolic elimination, and related clinical implications. Cannabinoids in Neurology and Psychiatry, vol. 34, pg. 795-800, (2020).

5. Perucca & Bialer. Critical aspects affecting cannabidiol oral bioavailability and metabolic elimination, and related clinical implications. Cannabinoids in Neurology and Psychiatry, vol. 34, pg. 795-800, (2020).


The future of CBD-based therapies

Low and variable bio-accessibility of CBD presents formulation challenges for the pharmaceutical industry. DSM is exploring drug delivery technologies to increase the molecule's pharmacokinetic profile. In-vitro studies reveal a strong correlation between bio-accessibility, physical state, stability, solubility, and particle size. Ongoing in-vivo work investigates excipients and formulation technology to identify candidates for clinical validation and product development. Learn how new research expands on the therapeutic benefits of CBD for the pharmaceutical industry.