Komal Komal, Hanton Lyall R, Glass Michelle, Das Shyamal C
School of Pharmacy, University of Otago, Dunedin 9054, New Zealand.
Department of Chemistry, University of Otago, Dunedin 9054, New Zealand.
Pharmaceutics. 2025 Aug 27;17(9):1120. doi: 10.3390/pharmaceutics17091120.
Inhaled delivery of cannabidiol (CBD) through dry powder inhalers is a promising approach for achieving optimal drug concentrations in the lungs. Spray drying is a commonly employed technique to prepare inhalable powders with particle sizes ideally ranging from 1 to 5 µm, for deep lung deposition. However, formulating aerosolizable CBD dry powders remains challenging due to the thermolabile nature of CBD and the cohesive behaviour of micron-sized particles, which affects powder dispersibility, reduces de-agglomeration during inhalation, and causes inefficient lung deposition. These challenges can be overcome by the inclusion of excipients that can stabilize CBD during processing and enhance the dispersion and aerosolization of the powder. This study investigates the role of different amino acids (lysine, cysteine, arginine, and phenylalanine) in combination with inulin, a sugar-based excipient, on the in vitro aerosolization performance, stability, and cytotoxicity of inhalable CBD dry powders. The prepared CBD dry powders exhibited a size range of 1-5 µm. Amino-acid-free CBD powder showed an irregular and flaky morphology, while in association with amino acids, CBD dry powder showed spherical morphology with a dimpled surface. The ATR-FTIR spectra confirmed no interactions between CBD and amino acids in the dry powder formulations. CBD dry powder formulations containing amino acids demonstrated a better aerosolization profile compared to amino-acid-free CBD powder, with the lysine-containing formulation achieving the highest fine particle fraction (FPF) of 56.6%. Additionally, all the formulations were stable under low and high humidity (<15% RH and 53% RH) conditions for 28 days. Cytotoxicity studies on A549 alveolar basal epithelial cells showed that the amino acids were non-toxic, while the CBD formulations with/without amino acids showed comparable levels of cytotoxicity.
通过干粉吸入器吸入递送大麻二酚（CBD）是在肺部实现最佳药物浓度的一种有前景的方法。喷雾干燥是一种常用技术，用于制备粒径理想范围为1至5微米的可吸入粉末，以实现肺部深部沉积。然而，由于CBD的热不稳定性质以及微米级颗粒的内聚行为，配制可雾化的CBD干粉仍然具有挑战性，这会影响粉末的分散性，减少吸入过程中的解聚，并导致肺部沉积效率低下。通过加入在加工过程中可以稳定CBD并增强粉末分散和雾化的辅料，可以克服这些挑战。本研究调查了不同氨基酸（赖氨酸、半胱氨酸、精氨酸和苯丙氨酸）与基于糖的辅料菊粉联合使用对可吸入CBD干粉的体外雾化性能、稳定性和细胞毒性的作用。制备的CBD干粉粒径范围为1至5微米。不含氨基酸的CBD粉末呈现不规则片状形态，而与氨基酸结合时，CBD干粉呈现表面有凹坑的球形形态。衰减全反射傅里叶变换红外光谱（ATR-FTIR）证实，在干粉制剂中CBD与氨基酸之间没有相互作用。与不含氨基酸的CBD粉末相比，含有氨基酸的CBD干粉制剂表现出更好的雾化特性，含赖氨酸的制剂实现了最高的细颗粒分数（FPF），为56.6%。此外，所有制剂在低湿度和高湿度（<15%相对湿度和53%相对湿度）条件下28天内均保持稳定。对A549肺泡基底上皮细胞的细胞毒性研究表明，氨基酸无毒，而含/不含氨基酸的CBD制剂表现出相当的细胞毒性水平。
