A gelatin matrix pellet formulation (PTL101) delivered 34% more CBD into the bloodstream than the equivalent dose of Sativex oromucosal spray, with a comparable safety profile in healthy volunteers.
Read this if you use CBD and are interested in how different formulations affect how much actually gets into your system.
134% relative bioavailability compared to Sativex spray
What the researchers found
Researchers tested a new oral CBD formulation called PTL101, which embeds highly purified CBD in seamless gelatin matrix beadlets, against Sativex oromucosal spray as a reference product. In a randomized crossover study with healthy volunteers, the 10 mg PTL101 dose produced 1.7 times higher peak blood levels and 1.3 times higher overall CBD exposure compared to the spray.
The time to reach peak blood levels was similar for both formulations at 3 to 3.5 hours, though PTL101 showed about a 1-hour lag in initial absorption. When the dose was increased from 10 mg to 100 mg, the resulting blood levels increased approximately 15-fold, slightly more than proportional to the dose increase.
Both formulations were well tolerated with no notable safety concerns, establishing PTL101 as a potentially more efficient oral delivery system for CBD.
Why it matters
CBD bioavailability has been a persistent challenge in cannabinoid medicine. Oral CBD typically has low absorption, with much of the dose lost to first-pass metabolism. A formulation that delivers more CBD into the bloodstream from the same dose could improve therapeutic outcomes and reduce the amount of CBD patients need to take.
The numbers in context
PTL101 10 mg vs Sativex: 1.7-fold higher Cmax, 1.3-fold higher AUC. Relative bioavailability of PTL101: 134% compared to Sativex. Tmax: 3-3.5 hours for both. 10-fold dose increase (10 to 100 mg) produced approximately 15-fold increase in Cmax and AUC. 1-hour absorption lag with PTL101.
How the study worked
This was a randomized, crossover, single-dose pharmacokinetic study in healthy volunteers comparing PTL101 (gelatin matrix pellet CBD formulation) at 10 mg and 100 mg doses with Sativex oromucosal spray as a reference product. Blood samples were collected at multiple time points to measure CBD pharmacokinetic parameters including Cmax, AUC, and Tmax.
What this study cannot tell us
This was a single-dose study in healthy volunteers, not patients with conditions that CBD is used to treat. The sample size was small. Long-term safety and repeated dosing were not assessed. The enhanced bioavailability needs to be confirmed to translate to improved clinical outcomes. Food effects were not evaluated.
How to read the evidence
This is a small randomized crossover pharmacokinetic study in healthy volunteers, providing preliminary evidence of improved CBD delivery.
When this study was published
Published in 2018. PTL101 and similar CBD delivery technologies have continued to develop.
The bigger picture
Improving CBD delivery is a significant focus of pharmaceutical development. Many patients find existing formulations require high doses to achieve therapeutic effects. Technologies like gelatin matrix pellets that enhance bioavailability could make CBD-based treatments more practical and cost-effective.
Questions still open
- Does the enhanced bioavailability of PTL101 translate to improved clinical outcomes in conditions like epilepsy? How does food intake affect PTL101 absorption compared to other CBD formulations? What is the optimal dose of PTL101 for specific therapeutic applications?
Common questions
Does the form of CBD matter for how well it works?
Why is CBD hard to absorb?
Read the original research
Single-Dose Pharmacokinetics of Oral Cannabidiol Following Administration of PTL101: A New Formulation Based on Gelatin Matrix Pellets Technology.
Clinical pharmacology in drug development, 7(7), 751-758
Citation
Atsmon, Jacob; Heffetz, Daphna; Deutsch, Lisa; Deutsch, Frederic; Sacks, Hagit. (2018). Single-Dose Pharmacokinetics of Oral Cannabidiol Following Administration of PTL101: A New Formulation Based on Gelatin Matrix Pellets Technology.. Clinical pharmacology in drug development, 7(7), 751-758. https://doi.org/10.1002/cpdd.408
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