Engineering Research Centre of Advanced Powder Technology (ERCAPT), School of Chemical and Environmental Engineering, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou, Jiangsu Province, 215123, PR China.
Pharm Res. 2024 Oct;41(10):2057-2073. doi: 10.1007/s11095-024-03770-7. Epub 2024 Oct 11.
Insomnia is a major health concern, and melatonin (MLT) is key for initiating sleep. Delivering MLT nasally can enhance brain bioavailability by targeting the olfactory region. This study aimed to fabricate MLT embedded microparticles for nasal delivery.
MLT-cyclodextrin (CD) derivatives complex microparticles (MCCMPs) were fabricated by spray drying and spray freeze drying MLT and CD derivative solutions. Phase solubility and H-H ROSEY NMR analysis assessed MLT-CD assembly. The effects of formulation compositions and process parameters on microparticle structural attributes were investigated. The in vitro nasal release and deposition performances were evaluated by a modified paddle-over-disk apparatus and 3D-printed nasal cavity cast, respectively.
Sodium sulphobutylether-β-cyclodextrin (SBE-β-CD) exhibited the best complexation ability with MLT, with the indole structure of MLT included in its cavity. Spray dried MCCMPs showed dense structure with high density, while the spray freeze dried counterpart showed the brittle and porous structure with low density. Despite the porous structure may promote the release rate of spray freeze dried samples, the high hydrophilicity of the CD derivative overshadows this advantage. Samples prepared by spray drying not only exhibited rapid release rates but also could deposit more effectively in the olfactory region, as they avoid breakage due to their higher mechanical strength. The optimal sample showed ~ 86.70% of the MLT released at 20 min and ~ 10.57% of the deposition fraction in the olfactory region.
This work compares MCCMPs fabricated by spray drying and spray freeze drying, providing the optimal formulation and process combinations.
失眠是一个主要的健康问题，而褪黑素（MLT）是启动睡眠的关键。通过靶向嗅觉区域，将 MLT 经鼻给药可以提高大脑的生物利用度。本研究旨在制备用于经鼻给药的 MLT 嵌入微粒。
通过喷雾干燥和喷雾冷冻干燥 MLT 和 CD 衍生物溶液来制备 MLT-环糊精（CD）衍生物复合微粒（MCCMPs）。相溶解度和 H-H ROSEY NMR 分析评估了 MLT-CD 组装。考察了制剂组成和工艺参数对微粒结构特性的影响。通过改进的桨叶-盘装置和 3D 打印的鼻腔铸型分别评估了体外鼻内释放和沉积性能。
磺丁基醚-β-环糊精（SBE-β-CD）与 MLT 具有最佳的络合能力，MLT 的吲哚结构被包含在其腔中。喷雾干燥的 MCCMPs 表现出致密的结构，密度高，而喷雾冷冻干燥的对应物表现出脆性多孔的结构，密度低。尽管多孔结构可能会促进喷雾冷冻干燥样品的释放速率，但 CD 衍生物的高亲水性掩盖了这一优势。通过喷雾干燥制备的样品不仅表现出快速的释放速率，而且能够更有效地沉积在嗅觉区域，因为它们避免了由于机械强度较高而破裂。最佳样品在 20 分钟时释放了约 86.70%的 MLT，在嗅觉区域的沉积分数约为 10.57%。
本工作比较了喷雾干燥和喷雾冷冻干燥制备的 MCCMPs，提供了最佳的配方和工艺组合。
