Physicochemical Properties, Heavy Metal and Pesticide Contaminations, and Microbial Limit Tests of Cannabis Oral Drops

Natawat Chankana; Chaowalit Monton; Surang Leelawat; Thanapat Songsak; Worawan Saingam; Fameera Madaka; Athip Maha; Pathamaporn Pathompak

doi:10.59796/jcst.V14N3.2024.61

Authors

Natawat Chankana Sun Herb Thai Chinese Manufacturing, College of Pharmacy, Rangsit University, Pathum Thani 12000, Thailand. & Medicinal Cannabis Research Institute, College of Pharmacy, Rangsit University, Pathum Thani 12000, Thailand.
Chaowalit Monton Medicinal Cannabis Research Institute, College of Pharmacy, Rangsit University, Pathum Thani 12000, Thailand. & Drug and Herbal Product Research and Development Center, College of Pharmacy, Rangsit University, Pathum Thani 12000, Thailand. & Department of Pharmacognosy, College of Pharmacy, Rangsit University, Pathum Thani 12000, Thailand.
Surang Leelawat Medicinal Cannabis Research Institute, College of Pharmacy, Rangsit University, Pathum Thani 12000, Thailand. & Department of Pharmacognosy, College of Pharmacy, Rangsit University, Pathum Thani 12000, Thailand.
Thanapat Songsak Medicinal Cannabis Research Institute, College of Pharmacy, Rangsit University, Pathum Thani 12000, Thailand. & Department of Pharmacognosy, College of Pharmacy, Rangsit University, Pathum Thani 12000, Thailand.
Worawan Saingam Medicinal Cannabis Research Institute, College of Pharmacy, Rangsit University, Pathum Thani 12000, Thailand. & Drug and Herbal Product Research and Development Center, College of Pharmacy, Rangsit University, Pathum Thani 12000, Thailand.
Fameera Madaka Medicinal Cannabis Research Institute, College of Pharmacy, Rangsit University, Pathum Thani 12000, Thailand. & Drug and Herbal Product Research and Development Center, College of Pharmacy, Rangsit University, Pathum Thani 12000, Thailand.
Athip Maha Medicinal Cannabis Research Institute, College of Pharmacy, Rangsit University, Pathum Thani 12000, Thailand.
Pathamaporn Pathompak Medicinal Cannabis Research Institute, College of Pharmacy, Rangsit University, Pathum Thani 12000, Thailand. & Drug and Herbal Product Research and Development Center, College of Pharmacy, Rangsit University, Pathum Thani 12000, Thailand.

DOI:

https://doi.org/10.59796/jcst.V14N3.2024.61

Keywords:

cannabidiol, delta-9-tetrahydrocannabinol, supercritical carbon dioxide fluid, quality

Abstract

Cannabis, a medicinal herb renowned for its therapeutic potential, is utilized in the treatment of various ailments, including the stimulation of appetite in cancer patients. In Thailand, the predominant dosage form is oral drops; however, the absence of robust quality control measures for these products poses significant health risks to patients. The primary objectives of this study were to formulate and evaluate cannabis oral drops, with a comprehensive evaluation encompassing physicochemical properties such as appearance, pH, Δ⁹-tetrahydrocannabinol, and cannabidiol contents. Furthermore, heavy metals (specifically arsenic, cadmium, and lead), pesticides (including pyrethroids, organochlorines, organophosphates, and carbamates), and microbial contaminations (Staphylococcus aureus, Clostridium spp., and Salmonella spp.) were evaluated. The results revealed that the optimal formulation, comprising cannabis extract derived from supercritical carbon dioxide fluid, vitamin E acetate, and medium-chain triglyceride oil, exhibited a pH of approximately 4.0, a Δ⁹-tetrahydrocannabinol content of approximately 27 mg/mL, and a cannabidiol content of approximately 9 mg/mL. Furthermore, there were no heavy metals or pesticides detected. Microbial limit tests demonstrated the absence of Staphylococcus aureus, Clostridium spp., and Salmonella spp. In conclusion, this endeavor successfully achieved the development of high-quality cannabis oral drops, showcasing the potential for safe and therapeutic use.

References

Aviram, J., & Samuelly-Leichtag, G. (2017). Efficacy of cannabis-based medicines for pain management: A systematic review and meta-analysis of randomized controlled trials. Pain Physician, 20(6), E755-E796. https://doi.org/10.36076/ppj.20.5.E755

Bilbao, A., & Spanagel, R. (2022). Medical cannabinoids: a pharmacology-based systematic review and meta-analysis for all relevant medical indications. BMC Medicine, 20(1), Article 259. https://doi.org/10.1186/s12916-022-02459-1

Bureau of Drugs and Narcotics. (2021). Thai Herbal Pharmacopoeia 2021. Retrieved November 18, 2023, from https://bdn.go.th/thp/ebook/qQEcAUtkpR9gC3q0GT5gMJq0qT5co3uw

Charoenying, T., Lomwong, K., Boonkrong, P., & Kruanamkam, W. (2023). Therapeutic potential of topical cannabis for the treatment of psoriasis: A preliminary clinical evaluation of two different formulations. Journal of Current Science and Technology, 14(1), Article 6. https://doi.org/10.59796/jcst.V14N1.2024.6

Hazekamp, A., Ware, M. A., Muller-Vahl, K. R., Abrams, D., & Grotenhermen, F. (2013). The medicinal use of cannabis and cannabinoids--an international cross-sectional survey on administration forms. Journal of Psychoactive Drugs, 45(3), 199-210. https://doi.org/10.1080/02791072.2013.805976

Machado Rocha, F. C., Stefano, S. C., De Cassia Haiek, R., Rosa Oliveira, L. M., & Da Silveira, D. X. (2008). Therapeutic use of Cannabis sativa on chemotherapy-induced nausea and vomiting among cancer patients: systematic review and meta-analysis. European Journal of Cancer Care, 17(5), 431-443. https://doi.org/10.1111/j.1365-2354.2008.00917.x

Madras, B. K. (2015). Update of cannabis and its medical use. Retrieved January 13, 2020, from https://www.who.int/medicines/access/controlled-substances/6_2_cannabis_update.pdf

Martin-Sanchez, E., Furukawa, T. A., Taylor, J., & Martin, J. L. (2009). Systematic review and meta-analysis of cannabis treatment for chronic pain. Pain Medicine, 10(8), 1353-1368. https://doi.org/10.1111/j.1526-4637.2009.00703.x

Medicines Regulation Division. (2004). Announcement from the Thai Food and Drug Administration: Consideration criteria for regulatory affairs concerning traditional medicines, focusing on microbial and heavy metal contaminations. Retrieved November 18, 2023, from https://drug.fda.moph.go.th/announcement-administration/6-fda-20040325

Ministry of Public Health. (2022). Announcement from the Thai Ministry of Public Health: Standard criteria, purity, and other characteristics crucial for the quality of registered, informed, or notified herbal products. Retrieved November 18, 2023, from https://www.ratchakitcha.soc.go.th/DATA/PDF/2564/E/294/T_0006.PDF

Monton, C., Chankana, N., Leelawat, S., Suksaeree, J., & Songsak, T. (2022). Optimization of supercritical carbon dioxide fluid extraction of seized cannabis and self-emulsifying drug delivery system for enhancing the dissolution of cannabis extract. The Journal of Supercritical Fluids, 179, Article 105423. https://doi.org/10.1016/j.supflu.2021.105423

Monton, C., Madaka, F., Settharaksa, S., Wunnakup, T., Suksaeree, J., & Songsak, T. (2019). Optimal condition of cannabis maceration to obtain the high cannabidiol and Δ9-tetrahydrocannabinol content. Anais da Academia Brasileira de Ciências, 91(3), Article e20190676. https://doi.org/10.1590/0001-3765201920190676

Nugent, S. M., Morasco, B. J., O'Neil, M. E., Freeman, M., Low, A., Kondo, K., ... & Kansagara, D. (2017). The effects of cannabis among adults with chronic pain and an overview of general harms: a systematic review. Annals of internal medicine, 167(5), 319-331. https://doi.org/10.7326/m17-0155

Pamplona, F. A., da Silva, L. R., & Coan, A. C. (2018). Potential clinical benefits of CBD-rich cannabis extracts over purified CBD in treatment-resistant epilepsy: Observational data meta-analysis. Frontiers in Neurology, 9, Article 759. https://doi.org/10.3389/fneur.2018.00759

Radwan, M. M., ElSohly, M. A., El-Alfy, A. T., Ahmed, S. A., Slade, D., Husni, A. S., ... & Ross, S. A. (2015). Isolation and pharmacological evaluation of minor cannabinoids from high-potency Cannabis sativa. Journal of Natural Products, 78(6), 1271-1276. https://doi.org/10.1021/acs.jnatprod.5b00065

Sena, W., Kessomboon, P., Pisutthigoson, M., Poolpoem, W., Thaenkham, T., & Seevathee, K. (2023). Decision-making experiences to use medicinal cannabis: Perspectives from patients with knee osteoarthritis and their care providers. Journal of Current Science and Technology, 14(1), Article 4. https://doi.org/10.59796/jcst.V14N1.2024.4

Shah, N. D., & Limketkai, B. N. (2017). The use of medium-chain triglycerides in gastrointestinal disorders. Retrieved May 7, 2024, from https://med.virginia.edu/ginutrition%20/wp-content/uploads/sites/199/2014/06/Parrish-February-17.pdf

Solmi, M., De Toffol, M., Kim, J. Y., Choi, M. J., Stubbs, B., Thompson, T., ... & Dragioti, E. (2023). Balancing risks and benefits of cannabis use: umbrella review of meta-analyses of randomised controlled trials and observational studies. BMJ, 382, Article e072348. https://doi.org/10.1136/bmj-2022-072348

Stockings, E., Campbell, G., Hall, W. D., Nielsen, S., Zagic, D., Rahman, R., ... & Degenhardt, L. (2018a). Cannabis and cannabinoids for the treatment of people with chronic noncancer pain conditions: a systematic review and meta-analysis of controlled and observational studies. Pain, 159(10), 1932-1954. https://doi.org/10.1097/j.pain.0000000000001293

Stockings, E., Zagic, D., Campbell, G., Weier, M., Hall, W. D., Nielsen, S., ... & Degenhardt, L. (2018b). Evidence for cannabis and cannabinoids for epilepsy: a systematic review of controlled and observational evidence. Journal of Neurology, Neurosurgery and Psychiatry, 89(7), 741-753. https://doi.org/10.1136/jnnp-2017-317168

Sucontphunt, A., Sueree, L., Jongrungruangchok, S., Maha, A., Madaka, F., Chankana, N., ... & Pradubyat, N. (2022). Validation and comparison of method using different wavelength detection at 210 and 228 nm for quantitative analysis of CBD in sublingual cannabis oil products. Interprofessional Journal of Health Sciences, 20(1-2), 28-35.

Wang, L., Zhang, Y., Chen, J.-F., Luo, Y.-Y., Zou, C.-X., Qin, L.-K., & Jia, Y.-L. (2023). Study on preparation and properties of Camellia oleifera seed oil microcapsules by complex coacervation and spray drying. LWT, 184, Article 115056. https://doi.org/10.1016/j.lwt.2023.115056

Ware, M. A., Wang, T., Shapiro, S., Robinson, A., Ducruet, T., Huynh, T., ... & Collet, J. P. (2010). Smoked cannabis for chronic neuropathic pain: a randomized controlled trial. Canadian Medical Association Journal, 182(14), E694-E701. https://doi.org/10.1503/cmaj.091414

Whiting, P. F., Wolff, R. F., Deshpande, S., Di Nisio, M., Duffy, S., Hernandez, A. V., ... & Kleijnen, J. (2015). Cannabinoids for medical use: A systematic review and meta-analysis. JAMA, 313(24), 2456-2473. https://doi.org/10.1001/jama.2015.6358

Yangsud, J., Ahkkarachinoreh, P., Santasanasuwan, S., Suksaeree, J., Songsak, T., Maha, A., ... & Monton, C. (2021). Effect of vegetable oil types on the stability of cannabinoids in cannabis sublingual drops. Journal of Current Science and Technology, 11(1), 15-23. https://doi.org/10.14456/jcst.2021.4

Zhang, H., Zhang, J., & Streisand, J. B. (2002). Oral mucosal drug delivery. Clinical Pharmacokinetics, 41(9), 661-680. https://doi.org/10.2165/00003088-200241090-00003