“Cannabidiol (CBD), a non-psychoactive cannabinoid, has shown therapeutic potential for treating inflammatory respiratory diseases such as chronic obstructive pulmonary disease and asthma.
However, the therapeutic efficacy of CBD is limited by extensive hepatic metabolism and low oral bioavailability (approximately 20 %). These problems can be overcome by choosing an appropriate targeted drug delivery system. Delivering CBD to the lungs via a dry powder formulation could be an effective method to achieve adequate concentration and therapeutic efficacy.
This study aims to develop a dry powder formulation of CBD with Inulin (INU) and L-leucine (LEC) using spray drying and to characterize its physicochemical and aerodynamic properties.
A design of experiments (DOE) approach was used to optimize the formulation by varying feed concentration (0.2 % w/v to 0.8 % w/v), LEC concentration (5 % w/w to 20 % w/w), and CBD concentration (5 % w/w to 20 % w/w).
The resulting CBD dry powder formulations exhibited a wrinkled morphology with particle sizes ranging from 1 to 5 µm and displayed a crystalline structure, as determined by powder X-ray diffraction. The response surface method (RSM) showed that increasing the feed concentration correlated with higher yields of the CBD formulations. Specifically, the formulation with a feed concentration of 0.8 % w/v achieved a yield of 61 %.
The aerosolization data demonstrated a direct relationship between the Fine Particle Fraction (FPF) and LEC concentration, indicating that FPF increases as the LEC concentration increases. The highest FPF of 62 % was achieved with a 20 % w/w LEC concentration and a feed concentration of 0.2 % w/v. Based on this, LEC plays a crucial role in enhancing aerosolization efficiency. While feed concentration negatively affects FPF, lower feed concentrations lead to an increase in FPF.
The Fine Particle Dose (FPD) varied with the concentration of CBD, with higher concentrations resulting in a higher FPD. A 28 days stability study under different humidity conditions (<15 % and 53 %) confirmed the stability of the CBD formulations. INU and LEC exhibited minimal cytotoxicity on A549 cells, while the raw CBD and CBD formulations showed comparable levels of cytotoxicity, pIC50 4.5 ± 0.3 and 4.2 ± 0.2.
Interestingly, the CBD dry powder formulations significantly reduced inflammation (pEC50 = 4.9) induced by lipopolysaccharide (LPS).
These findings suggest that an inhalable formulation of CBD, incorporating LEC and INU, has been successfully developed. The formulations demonstrated improved aerosolization properties, stability, and promising anti-inflammatory effects, potentially making them a viable therapeutic option for inflammatory lung diseases.”
https://pubmed.ncbi.nlm.nih.gov/40578460/
“This study successfully developed a stable and effective dry powder formulation of CBD for inhalation, which could have the potential to treat COPD and other inflammatory respiratory diseases.”
https://www.sciencedirect.com/science/article/abs/pii/S037851732500729X?via%3Dihub
“The Endocannabinoid System (ECS) is primarily responsible for maintaining homeostasis, a balance in internal environment (temperature, mood, and immune system) and energy input and output in living, biological systems. 
“Genus Cannabis belong to family Cannabaceae and is traditionally used as medicinal plant against many diseases notably asthma, malaria, treatment of skin diseases, diabetes and headache. The plant Cannabis sativa L. is flowering and an annual herbaceous plant located to eastern Asia but now of cosmopolitan distribution due to extensive cultivation.
“Asthma is characterized by chronic lung inflammation and airway hyperresponsiveness. Asthma remains a major public health problem and, at present, there are no effective interventions capable of reversing airway remodelling.
“Cannabinoids are naturally occurring compounds, derivatives of Indian hemp, in which tetrahydrocannabinol (THC) is the most important. Marijuana, hashish and hash oil are among those most commonly used in the group.
Cannabinoids (marjhuana and hashish) have been used throughout recorded history as effective drugs in treating various diseases and conditions such as: malaria, hypertension, constipation, bronchial asthma, rheumatic pains, and as natural pain relief in labour and joint pains.
Marijuana acts through cannabinoid receptors CB 1 and CB2. Both receptors inhibit cAMP accummulation (through Gi/o proteins) and stimulate mitrogen- activated protein kinase. CB1 rceptors are located in CNS and in adipose tissue, digestive tract, muscles, heart, lungs, liver, kidneys, gonads, prostate gland and other peripheral tissues. CB2 cannabinoid receptors are located in the peripheral nervous system (at the ends of peripheral nerves), and on the surfaces of the cells of the immunological system.
The discovery of endogenous cannabinoids has contributed to a better understanding of their role in the regulation of the intake of food, energetic homeostasis and their significant influence on the endocrine system.”
“After experimental induction of acute bronchospasm in 8 subjects with clinically stable bronchial asthma, effects of 500 mg of smoked marijuana (2.0 per cent delta9-tetrahydrocannabinol) on specific airway conductance and thoracic gas volume were compared with those of 500 mg of smoked placebo marijuana (0.0 per cent delta9-tetrahydrocannabinol), 0.25 ml of aerosolized saline, and 0.25 ml of aerosolized isoproterenol (1,250 mug).
After methacholine-induced bronchospasm, placebo marijuana and saline inhalation produced minimal changes in specific airway conductance and thoracic gas volume, whereas 2.0 per cent marijuana and isoproterenol each caused a prompt correction of the bronchospasm and associated hyperinflation. After exercise-induced bronchospasm, placebo marijuana and saline were followed by gradual recovery during 30 to 60 min, whereas 2.0 per cent marijuana and isoproterenol caused an immediate reversal of exercise-induced asthma and hyperinflation.”