Fabrication of Uniform Melatonin Microparticles Potentially for Nasal Delivery: A Comparison of Spray Drying and Spray Freeze Drying.

IF 3.5 3区医学 Q2 CHEMISTRY, MULTIDISCIPLINARY Pharmaceutical Research Pub Date : 2024-10-01 Epub Date: 2024-10-11 DOI:10.1007/s11095-024-03770-7

Chengzhi You, Shen Yan, Mengyuan Li, Shuaiyu Xie, Shengyu Zhang, Xiao Dong Chen, Winston Duo Wu

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Abstract

Purpose: 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.

Methods: MLT-cyclodextrin (CD) derivatives complex microparticles (MCCMPs) were fabricated by spray drying and spray freeze drying MLT and CD derivative solutions. Phase solubility and ¹H-¹H 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.

Results: 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.

Conclusions: This work compares MCCMPs fabricated by spray drying and spray freeze drying, providing the optimal formulation and process combinations.

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制作可用于鼻腔给药的均匀褪黑素微粒：喷雾干燥法与喷雾冷冻干燥法的比较。

目的：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。鼻腔给药褪黑素可通过靶向嗅区提高大脑生物利用率。本研究旨在制造用于鼻腔给药的嵌入式褪黑素微粒：方法：通过喷雾干燥和喷雾冷冻干燥 MLT 和 CD 衍生物溶液，制备出 MLT-环糊精（CD）衍生物复合微颗粒（MCCMPs）。相溶性和 1H-1H ROSEY NMR 分析评估了 MLT-CD 的组装情况。研究了配方成分和工艺参数对微粒结构属性的影响。体外鼻腔释放和沉积性能分别通过改良的桨-盘仪器和三维打印鼻腔模型进行了评估：结果：硫代丁基醚-β-环糊精钠（SBE-β-CD）与MLT的络合能力最强，其空腔中含有MLT的吲哚结构。喷雾干燥的 MCCMPs 具有高密度的致密结构，而喷雾冷冻干燥的 MCCMPs 则具有低密度的脆性多孔结构。尽管多孔结构可以提高喷雾冷冻干燥样品的释放率，但 CD 衍生物的高亲水性掩盖了这一优势。喷雾干燥法制备的样品不仅释放速度快，而且由于其机械强度较高，可避免破损，因此能更有效地沉积在嗅觉区域。最佳样品在 20 分钟内释放了约 86.70% 的 MLT，在嗅觉区域沉积了约 10.57%：本研究比较了喷雾干燥法和喷雾冷冻干燥法制造的 MCCMP，提供了最佳配方和工艺组合。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pharmaceutical Research 医学-化学综合

CiteScore

6.60

自引率

5.40%

发文量

276

审稿时长

3.4 months

期刊介绍： Pharmaceutical Research, an official journal of the American Association of Pharmaceutical Scientists, is committed to publishing novel research that is mechanism-based, hypothesis-driven and addresses significant issues in drug discovery, development and regulation. Current areas of interest include, but are not limited to: -(pre)formulation engineering and processing- computational biopharmaceutics- drug delivery and targeting- molecular biopharmaceutics and drug disposition (including cellular and molecular pharmacology)- pharmacokinetics, pharmacodynamics and pharmacogenetics. Research may involve nonclinical and clinical studies, and utilize both in vitro and in vivo approaches. Studies on small drug molecules, pharmaceutical solid materials (including biomaterials, polymers and nanoparticles) biotechnology products (including genes, peptides, proteins and vaccines), and genetically engineered cells are welcome.