(M1230-01-02) Formulation Development and Evaluation of Cannabidiol Oral Film Using Antisolvent and Solvent Casting Approaches

Purpose: Cannabidiol (CBD) is a phytocannabinoid isolated from Cannabis sativa. CBD has been approved for its antiepileptic therapeutic effect in pediatrics by the FDA and it has also been studied for its anti-inflammatory, analgesic, anxiolytic, and antipsychotic activities Although CBD has a wide range of potential therapeutic benefits, its use has been limited due to certain challenges. The major problems associated with CBD are its poor aqueous solubility and extensive first-pass metabolism resulting in low bioavailability (~6%). The objective of this project was to develop the immediate-release CBD oral film formulation to enhance the aqueous solubility of CBD using a combination of antisolvent precipitation and solvent-casting methods.

Methods: Various oral film formulations were developed using an accurate amount of CBD, different film-forming polymers, and excipients (Table 1). CBD solution was prepared by the antisolvent precipitation method. CBD (50 mg) was dissolved in ethanol and then added to an aqueous solution containing PEG 300, Cremophor EL, and Tween 80. The CBD solution was then transferred to an HPMC polymeric solution and stirred at 1000 rpm for two hours. The resulting mixture was casted onto a glass petri dish followed by drying at 40℃ for 24 hours to obtain a CBD oral film (Figure 1). Particle size (PS), film thickness, and disintegration time were examined. HPLC was used to assess the CBD content of the prepared films. To evaluate the mechanical robustness of the film, a folding endurance test was performed. The drug release characteristics of the CBD film were studied at 37°C in pH 6.8 phosphate buffer with 0.1% v/v tween 80. A 1.5 mL sample was drawn at 15, 30, 45, 60, 90, 120, and 150 minutes.

Results: The film thickness was found to be thin and uniform (0.08±0.01 mm), for the film containing HPMC K100 LV compared to films containing HPMC E5 and HPMC K100 M. Drug content results showed that approximately 20% of the CBD leached on the petri dish wall, whereas only 80% of the CBD was entrapped in the film. On the other hand, F1 and F2 showed a low CBD content, hence F3 was selected as a lead formulation for further evaluation. Particle size for pure CBD, CBD antisolvent solution, and F3 film were found to be 644.75± 5.67, 372.4 ± 2.10, and 350.75 ± 3.68 d.nm respectively. The disintegration time for the F3 film was found to be less than 60 secs. The folding endurance for F3 film was observed between 100 and 120 which indicates the high mechanical strength of the film. The drug release studies, as shown in Figure 2, revealed that F3 film had a rapid CBD release of 85% within 15 minutes, compared to only 10% for pure CBD.

Conclusion: A CBD oral film was fabricated using the combination of the antisolvent precipitation method and solvent casting method with an enhanced release profile compared to pure CBD. Overall, these results suggest that CBD-loaded oral film holds promise as an effective and convenient dosage form for CBD delivery. However, further research to increase the CBD drug loading in the film formulation is required to make CBD film an effective dosage form for CBD delivery.

References: 1. Raucci U, Pietrafusa N, Paolino MC, Di Nardo G, Villa MP, Pavone P, Terrin G, Specchio N, Striano P, Parisi P. Cannabidiol treatment for refractory epilepsies in pediatrics. Frontiers in Pharmacology. 2020 Sep 29;11:586110.
2. Gul W, Gul SW, Radwan MM, Wanas AS, Mehmedic Z, Khan II, Sharaf MH, ElSohly MA. Determination of 11 cannabinoids in biomass and extracts of different varieties of Cannabis using high-performance liquid chromatography. Journal of AOAC International. 2015 Nov 1;98(6):1523-8.
3. Zhang W, Xiao C, Xiao Y, Tian B, Gao D, Fan W, Li G, He S, Zhai G. An overview of in vitro dissolution testing for film dosage forms. Journal of Drug Delivery Science and Technology. 2022 Mar 29:103297.

Acknowledgements: We are grateful to Dr. Mahmoud A. ElSohly for providing the CBD and Dr. Mohamed M. Radwan for his valuable advice and guidance.

Table 1. Formulation composition for CBD-loaded films.

Figure 1: CBD-loaded oral films (F1, F2, and F3).

Figure 2: In vitro Dissolution Profile of F3 film and pure CBD.