(T1530-01-03) Influence of Composition Variation on Solubility and Release Profile of CBD Self-Emulsifying Drug Delivery System

Purpose: Cannabidiol (CBD) is a potential non-psychoactive drug that has many beneficial pharmacological effects including anti-inflammatory, antioxidant, anxiolytic, and antidepressant and it is FDA-approved for the treatment of refractory seizures in Lennox-Gastaut and Dravet Syndrome(1,2). CBD is a lipophilic drug, that has poor water solubility and low bioavailability and is affected by first-pass metabolism(3). Self-emulsifying Drug Delivery Systems (SEDDSs) increase drug solubility by enhancing drug dispersion in GIT fluid. Furthermore, it has a potential absorption through the intestinal lymphatic system(4). The aim of this study was to develop stable CBD SEDDs formulations that may boost CBD solubility and in vitro release by using excipients with the highest CBD solubility.

Methods: CBD solubility in different excipients (Tween^® 20, Tween^® 80, Kolliphor® EL, Labrasol®, Trancutol® HP, Plurol® oleique CC 497, Labrafil® M 1944 CS, sesame seed oil, and Capryol® 90) has been performed by dissolving an excess amount of CBD in 1 mL of each excipient. The samples were kept on a shaker at 100 rpm for 72 hours to attain equilibrium. The excipients with high CBD solubility were used to develop a pseudo-ternary phase diagram among caproyl 90, tween^® 20, and transcutol^® HP as oil, surfactant, and co-surfactant respectively. Sixteen placebo SEDDS formulations were prepared and evaluated for separation, emulsification time, particle size (PS), and polydispersity index (PDI). Five SEDDS formulations with the smallest PS and PDI were selected to load CBD. CBD SEDDS formulations were further characterized for emulsification time, PS, and PDI. Moreover, CBD SEDDS formulations were tested for their thermodynamic stability. The formulations were observed visually to determine any phase separation after centrifugation, and the freeze-thaw cycle was executed for 48 hours at (− 20°C, room temperature, and 40°C. In-vitro drug release was performed using USP apparatus in phosphate buffer at pH 6.8 (50 rpm and 37°C).

Results: CBD observed high solubility in tween^® 80, tween^® 20, kolliphor^® EL, transcutol^® HP, and capryol^® 90. SEDDS formulations prepared with tween® 80 were able to produce SEDDS with inconsistent PS and PDI. Thus, tween® 20, transcutol® HP, and capryol® 90 were used to construct the pseudo-ternary diagram (Figure 1). The pseudo-ternary diagram illustrated that upon emulsification, the placebo SEDDS formulations containing more than 40% w/w capryol® 90 tended to separate, and these formulations were not evaluated further. On the other hand, increasing the amount of tween<^® 20 by more than 40 % w/w gave an emulsion with small PS and PDI. All placebo SEDDS formulations show a short emulsification time of less than one minute as shown in table 1. The thermodynamic stability studies showed that all CBD SEDDS formulations were stable with no phase separation, precipitation, cracking, or coalescence. Furthermore, PS and emulsification time were not changed.
In-vitro release of CBD SEDDS (CTT4 and CTT12) showed increasing in the CBD drug release compared to pure CBD which was below the limit of the HPLC analytical detection (Figure 2). The SEDDS formulation with more tween^® 20 content (CTT4) exhibited a superior drug release in contrast to the SEDDS formulation with a lower tween^® 20 content (CTT12).

Conclusion: The results of the study demonstrated that the excipients had significant impacts on the CBD SEDDS's release performance. The use of tween^® 20, transcutol^® HP, and capryol^® 90 in the formulation of CBD SEDDS showed promise in improving the release and bioavailability of CBD.

References: 1. White CM. A Review of Human Studies Assessing Cannabidiol’s (CBD) Therapeutic Actions and Potential. Vol. 59, Journal of Clinical Pharmacology. Blackwell Publishing Inc.; 2019. p. 923–34.
2. Atalay S, Jarocka-karpowicz I, Skrzydlewskas E. Antioxidative and anti-inflammatory properties of cannabidiol. Vol. 9, Antioxidants. MDPI; 2020.
3. Perucca E, Bialer M. Critical Aspects Affecting Cannabidiol Oral Bioavailability and Metabolic Elimination, and Related Clinical Implications. CNS Drugs. 2020 Aug 1;34(8):795–800.
4. Kok LY, Bannigan P, Sanaee F, Evans JC, Dunne M, Regenold M, et al. Development and pharmacokinetic evaluation of a self-nanoemulsifying drug delivery system for the oral delivery of cannabidiol. European Journal of Pharmaceutical Sciences. 2022 Jan 1;168.


Table 1. Emulsification time, mean of particle size, and PDI of SEDDS placebo formulations. Each value represents the mean ± S.D. (n=3)


Figure 1 Pseudo-ternary phase diagram of SEEDS using capryol®90 as oil, tween® 20 as a surfactant, and transcutol® HP as a co-surfactant.


Figure 2. In-vitro release profiles of pure CBD and CBD SEDDS formulations (CTT4 and CTT12) in phosphate buffer pH 6.8