Formulation Considerations for Asthma Treatment with CBD MDI


Asthma is an incurable disease of the lungs. It causes the linings of the respiratory bronchiole of the lungs to swell with inflammation. The muscles around them can get tight causing an “exacerbation” of an asthma attack. Over time, effects of uncontrolled asthma such as increased inflammation and asthma attacks may have long-term effects on breathing and can lead to permanent damage. Worst case, death. CBD is an efficacious treatment of bronchial asthma (asthma), particularly via pulmonary administration. When formulating for a CBD for asthma treatment, specific strategies and considerations are critical.

Cannabis helps lung health.
PC: @elenatrn

Remove the Bias

Smoking cannabis for several years has had a bias against it that is as dangerous as smoking tobacco. There was a longitudinal study launched in 1985 and spanned 20 years the “Coronary Artery Risk Development in Young Adults” (CARDIA). It examined the pulmonary function of 5,115 people across four U.S. cities. CARDIA took into account smoking habits of both tobacco and marijuana (cannabis). All participants were healthy and between the ages of 18-30 at the time of enrollment. in 1985. Following a baseline examination, participants were then examined six times throughout the subsequent 20 years at specific year markers. In order to measure participants’ pulmonary function, researchers measured FEV1 (forced expiratory volume)—how much air somebody can exhale during a forced breath in the first second after taking as deep a breath as possible—and FVC (forced vital capacity)—the total amount of air exhaled during the FEV test after taking as deep a breath as possible.  Noteworthy is that the study was conducted on smoking of combustible plant material, not vaping cannabis extracts.

CARDI findings were significant. Firstly, the study reinforces previous studies on tobacco smoking and its harmful effects on lung health. Secondly, this is one of the longest and most intensive studies conducted on marijuana in regard to lung health, that cannabis use, in fact, helps lung health. 

The Science Behind the Delivery Method

There are four methods of cannabinoid inhalation: smoking, vaping, a metered dose inhaler (MDI) and a nebulizer. Inhaled cannabinoid therapy “pulmonary administration”, avoids first pass metabolism (bypassing metabolism in the liver) which might filter out the desired cannabinoids. When developing a cannabinoid therapy product for pulmonary administration, formulation strategies and considerations are required.

Pulmonary administration of drug inhalation enables a rapid and predictable onset of action and with fewer side effects than other routes of administration. Via the alveoli in the lungs, there is gas exchange between the blood capillaries and the gas which allows oxygen to cross cell membranes to oxygenate the blood and carbon dioxide is removed. The alveoli are tiny, balloon-shaped air sacs sitting at the very end of the respiratory “tree” and are arranged in clusters throughout the lungs.

Asthma leads to scarring in the lungs and sometimes, death.
PC: Getty Images

CBD is Class II in the Biopharmaceutical Classification System (BCS). It has low solubility and high permeability. BCS II yields low bioavailability. Class II compounds have high permeability meaning a better ability for the drug compound to cross a biological membrane, e.g. alveoli. The benefits of formulating CBD are increased water solubility; improved taste and odor; improved stability; improved bioavailability and overcome regulatory challenges

When formulating to treat specific diseases and disorders, consideration should include consumer preferences for optimal patient compliance focused on taste, odor and the ideal delivery method for the targeted patient population. Asthma patients are well familiar with MDI for the delivery mechanism of a synthetic pharmaceutical product and that would positively impact patient compliance. 

MDI Specifics + Benefits

Specific to CBD drug formulation specific to MDI delivery, critical considerations should be made including the physicochemical properties of CBD, lung biology, properties of CBD and additives/excipients. Delivery of CBD per the press of the MDI mechanism of the cartridge against a modulator is discreet. Additional benefits of MDI include:

  1. Delivery to lungs with one button push which benefits with measured dosing. 
  2. It’s combustion-less so there is no degradation of cutting agents.
  3. Utilizes the strength and power of a pure cannabis distillate while also maintaining a positive flavor profile. 
  4. MDI components are of pharmaceutical grade from the aluminum can to the propellant (HFA-134a which is the exact same propellant used in non-cannabinoid therapies).
A metered dose inhaler (MDI).

Via a MDI, the drug is either suspended or dissolved in a propellant that is pressurized until it liquefies in a canister. The liquefied propellant serves both as a source of energy for expelling the formulation from the valve in the form of rapidly evaporating droplets and as a dispersion medium for the drug and other excipients. CFC is a successful excipient for propellant-driven MDI but CFC is noteworthy for contribution to ozone depletion in the upper atmosphere and concomitant health effects. An excipient selected for its environmental impact, patient safety and success CBD delivery is paramount. 

CBD’s chemical structure evokes pharmacological actions. Pharmacokinetics (PK) properties, what a drug does to the body (ADMET), and pharmacodynamics, what the body does to the drug, should also be considered. First pass metabolism of CBD is avoided when delivered by inhalation which results in zero drug-drug interaction synthetic drug metabolism via enzyme CYP450, the enzyme found in the liver. When considering PK and pharmacodynamics, the receptors in the body should be included in formulation.  CBD is an agonist at CB2 receptor which results in decrease of inflammation, successfully treating asthma which is inflammation of the lungs. .

Cannabis Chemistry Considerations

Physico-chemical aspects including surface charge, size, shape and deformability should be considered. New formulation technology can be applied to affect the physico-chemical aspects. Pharmaceutical nanotechnology would be considered to improve the therapeutic efficacy of bioactive molecules. The benefit is a controlled, sustained and targeted drug delivery. Creating a sufficient surface area of the resulting CBD formulation is required to provide for single and rapid dispensing cycles of the formulation (including propellant) to maintain dose content uniformity, particle size distribution, and the comfort of the patient. 

The impact of excipients should be included in consideration. Excipients are the inactive substances that are used as the vehicle or medium for a drug. Also for consideration is the impact of the formulating agent. If the incorrect is selected, there may be interactions between excipients and the drug molecule that will alter the desired therapeutic benefit.

Treating asthma with a CBD MDI might be lifesaving.

Although the most expensive extraction method, CO2 -based extraction method is preferred versus oil-based or alcohol-based since it protects the cannabinoids and no toxic residuals remain. CO2 is a gas at room temperature and at other temperatures, can be used as a solvent. The benefits of CO2 extraction are it’s non-flammable, inert and non-toxic. Low levels of residuals remain after the extraction and can yield a CBD product that is purer as well as solvent free. This method solubilizes a significant proportion of active compounds. 

Following the CO2 extraction process, another purification process known as “winterization” is required. Winterization utilizes the very low temperature found in a freezer and an alcohol-based process for further refinement. This process does remove terpenes which have medicinal value but they can be added back in. The benefit of winterization is that it removes fats and waxes which are a problem for product solubility as well as chlorophyll (non-toxic but tastes bad and may deliver potentially unpleasant gastrointestinal side effects) yielding a product that is fairly pure with approximately 65% potency. 

Following winterization, further purification of the CBD product via distillation is required. Similar to CO2 extraction and winterization, terpenes are lost yet they can be added back in along the formulation process. The benefits of distillation and its high evaporation rates allow for more distillates to be captured while the relatively low processing temperatures (130-180°C) which contributes to the fact that there aren’t any solvents needed to move the extract material through the process. Most importantly, distillation can result in a CBD distillate that can be 99% pure. 

Even Better with Terpenes

Terpenes are the non-cannabinoids of the cannabis plant, the essential oils of most plants including the cannabis plant. Cannabis has a particularly high concentration of terpenes. They contribute to the “entourage effect” of cannabinoids, delivering added therapeutic benefits yet they are volatile and evaporate easily. Mostly found in the gaseous state, terpenes are removed throughout processing and it is necessary to them back into the CBD product prior to the final formulation steps for MDI delivery. Inclusion of specific terpenes which deliver anti-inflammatory effects and would improve the taste and smell include caryophyllene, a-pinene, myrcene, and humulene.

Jacquie Cohen Roth, MS is Founder/CEO of CannabizMD and Tea Pad. She is a member of the 2021 cohort of MS in Medical Cannabis Science and Therapeutics at the University of Maryland, School of Baltimore.


Pletcher, Mark J., et al (2012). Association between marijuana exposure and pulmonary function over 20 years. JAMA, 307(2), 173-181.

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Nagarkatti P, Pandey R, Rieder SA, Hegde VL, Nagarkatti M. Cannabinoids as novel anti-inflammatory drugs. Future Med Chem. 2009;1(7):1333–1349. doi:10.4155/fmc.09.93

Formulation Considerations of Inhaled Products. Published 2020. Accessed April 14, 2020.

Aaron LaBarbera,, accessed April 13, 2020.

Gressin-Delylel, S, et al, Cannabinoids inhibit cholinergic contraction in human airways through prejunctional CB1 receptors British Journal of Pharmacology, August 2013. Accessed April 13, 2020

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