Sodium Stearate-Assisted Optimization of a Cannabidiol Dry Powder Inhaler for Enhanced Dissolution and Aerosol Performance

Background/Objectives: Cannabidiol (CBD) has emerged as a potential therapeutic agent for respiratory disorders, including asthma and chronic obstructive pulmonary disease. However, its clinical translation via pulmonary delivery is limited by poor aqueous solubility, chemical instability, and low local bioavailability. This study aimed to develop and optimize a sodium stearate (NaSt)-based spray-dried dry powder inhaler (DPI) formulation to enhance the aerosol performance, dissolution, and storage stability of CBD. Methods: CBD microparticles were prepared by spray drying using NaSt as the primary excipient. The feed preparation method, spray-drying parameters, and CBD:NaSt ratios were systematically optimized. The resulting powders were evaluated for aerodynamic properties using cascade impaction, dissolution behavior in simulated lung fluid, solid-state characteristics, and accelerated stability under stress conditions. Results: The optimized formulation, SD-4, a spray-dried CBD:NaSt formulation prepared at a 20:80 weight ratio using Process B, demonstrated excellent aerosolization performance, with a fine particle fraction (FPF) exceeding 50% and a mass median aerodynamic diameter (MMAD) of 5.08 ± 0.1 μm. Dissolution testing revealed more than a three-fold increase in drug release compared with raw CBD, attributed to amorphous dispersion within the NaSt matrix and surfactant-induced micellization. Accelerated stability studies confirmed improved retention of the amorphous state and drug content, while antioxidant incorporation further reduced oxidative degradation. Conclusions: The NaSt-based spray-dried formulation significantly improved aerosol deposition efficiency, dissolution rate, and physicochemical stability of CBD. This formulation strategy may provide a promising platform for pulmonary delivery of poorly water-soluble compounds.