MCST603- Module 4 (Lecture 3): Formulation of cannabinoids for inhalation Cannabis Chemistry & Drug Delivery Ryan M. Pearson, PhD Assistant Professor Pharmaceutical Sciences Module Objectives 1. Explain basic lung physiology. 2. Describe how cannabinoids are formulated into inhalable forms 3. Discuss the pharmacokinetics of inhalable cannabinoids. Course Level Learning Objectives 1. Compare and contrast the available formulation strategies and considerations for preparing cannabinoids for inhalation. Methods for inhalation of cannabinoids Vaporizers • Smoking • Vaporizing • Metered dose inhaler • Nebulizer Smoking Inhalers Nebulization Smoking • The most common way of inhaling cannabinoids. • The quickest method to get cannabinoids into the bloodstream. • Smoke enters the lungs and is absorbed for immediate transport to the brain. • Dose delivered depends on multiple factors including potency, and length of inhale. Properties of flower • Contains desirable: • Cannabinoids • Terpenes • Flavenoids • Undesirable: • Lipids, fats, waxes • Chlorophyll Decarboxylation • • • • • Removal of a carboxylic acid group. Smoking or vaping rapidly removes the carboxyl group. CBD products are sold as activated products so the consumer does not need to worry about decarboxylation. Can be done before or after extraction from flower. Before extraction is preferred. https://www.liebertpub.com/doi/pdf/10.1089/can.2018.0067 Why is decarboxylation important? • The carboxylated species are less potent than decarboxylated species. • Achieving chemical consistency and biological activity is critical if cannabinoids are to become widely utilized pharmaceuticals. https://www.liebertpub.com/doi/pdf/10.1089/can.2018.0067 Extracting CBD and THC • Oil-based extraction - Edible oils such as olive oil, coconut oil. Storage is a concern and typically only used for tinctures or sprays). Low concentration. • Alcohol-based extraction – Butane, rice alcohol, isopropyl alcohol, hexane, ethanol. Not pure and safety concerns (i.e. explosion and residual solvents). Destroys plant fats and terpenes. Poor taste. • CO2-based extraction method – protects the cannabinoids and no toxic residuals remain (i.e. gentle). Expensive and complicated. Most large-scale manufacturers use this technique. CO2-based extraction • CO2 is a gas at room temperature, yet can be used as a solvent at other temperatures and pressures. • Supercritical CO2 behaves like a liquid and a gas. • This fluid is passed through the raw material. • Solubilizes a significant proportion of active compounds. • Consistency of peanut butter (supercritical). CO2-based extraction advantages • Non-flammable, inert, non-toxic. • Can be performed at near ambient temperature. • Low levels of residuals remain after processing. • More pure. • Solvent free. Refinement (Winterization) • A subsequent alcohol-based extraction process to purify products obtained by CO2 extraction. • • • • • • Alcohol extract is frozen (cold like winter) Cannabinoids are separated. Removes phytonutrients (such as terpenes). Removes fats and waxes (e.g. lipids from plants). Removes chlorophyll. Approximately 65% potency. https://cfh.ltd/understandingextraction Distillation Winterization Refinement (Distillation) • Short path distillation • Typically performed after winterization. • Oil is heated in a flask under vacuum (cannabinoids have high bp (156 to 250oC). • Condenser column collects vapor. • Additional terpene residuals are lost. • Can be performed multiple times. • 75-90% potency can be achieved. https://cdn2.hubspot.net/hubfs/547446/LX%20Landing%20Pag es/JULABO_whitepaper%20final-1.pdf Activities 1. Watch the three course videos 2. Blackboard “quiz” reviewing key module objectives. (10 multiple choice questions). Students retake until they reach a minimum score. Cite any external references used. (10 points). 3. Watch the Khan academy video on lung physiology:https://www.khanacademy.org/science/highschool-biology/hs-human-body-systems/hs-the-circulatory-and-respiratory-systems/v/meet-the-lungs 4. Review the slides: “Formulation considerations for inhalable products.” 5. Assignment: Write a two page essay that describes how you would formulate an inhalable CBD drug product. Discuss the relevant physicochemical properties, excipients, and delivery mechanism. Your suggestion cannot involve smoking or vaping as a means to deliver CBD. Post your essay by Sunday. (30 points). 6. Choose groups for Module 8 group project. Six students per group.