García-Arieta A, Torrado-Santiago S, Goya L, Torrado J J
Department of Pharmaceutical Technology, Faculty of Pharmacy, Complutense University, Madrid, Spain.
Biol Pharm Bull. 2001 Dec;24(12):1411-6. doi: 10.1248/bpb.24.1411.
The aim of this work is to describe and characterize a new spray-drying procedure for the production of nasal powders as an alternative to the conventional freeze-drying method. Cyanocobalamin was chosen as the active ingredient and loaded into five different nonsoluble vehicles with high water absorption ability. Then these hydrated particles were suspended in methylene chloride and spray-dried. Particle size, morphology, true, bulk and tapped density, percentage of compressibility, moisture content, water intake, and drug diffusion were studied and significant differences were obtained depending on the nature of the vehicle. The drying method, either the new spray- or the conventional freeze-drying, was less important. Interestingly, an inverse correlation was found between water uptake and drug diffusion. Microcrystalline cellulose, dextran microspheres, and crospovidone were chosen for an in vivo bioavailability study in rabbits. Three other nasal reference formulations and an intravenous solution were also administered. The spray-dried powders showed higher bioavailability than the three nasal reference formulations. The highest absorption enhancement was observed with cellulose microcrystalline powders, which provided a 25% mean absolute bioavailability, followed by crospovidone and dextran microspheres formulations with mean bioavailability values of 14% and 7%, respectively. In conclusion, the new spray-drying method is useful for the production of cyanocobalamin nasal powders.
本研究的目的是描述和表征一种用于生产鼻用粉剂的新型喷雾干燥工艺，作为传统冷冻干燥方法的替代方法。选择氰钴胺作为活性成分，并将其负载到五种具有高吸水能力的不同不溶性载体中。然后将这些水合颗粒悬浮在二氯甲烷中并进行喷雾干燥。研究了粒径、形态、真密度、松密度和振实密度、可压缩性百分比、水分含量、吸水量和药物扩散情况，并根据载体的性质获得了显著差异。干燥方法，无论是新型喷雾干燥还是传统冷冻干燥，都不太重要。有趣的是，发现吸水量与药物扩散之间存在负相关。选择微晶纤维素、葡聚糖微球和交联聚维酮进行兔体内生物利用度研究。还给予了另外三种鼻用参比制剂和一种静脉注射液。喷雾干燥粉末的生物利用度高于三种鼻用参比制剂。微晶纤维素粉末的吸收增强效果最高，其平均绝对生物利用度为25%，其次是交联聚维酮和葡聚糖微球制剂，平均生物利用度值分别为14%和7%。总之，新型喷雾干燥方法可用于生产氰钴胺鼻用粉剂。
