Laboratory of Solids Process Engineering, TU Dortmund University, Germany.
Laboratory of Solids Process Engineering, TU Dortmund University, Germany.
Int J Pharm. 2019 Aug 15;567:118501. doi: 10.1016/j.ijpharm.2019.118501. Epub 2019 Jul 6.
Manufacturing poorly water-soluble active pharmaceutical ingredients (API) with sufficient bioavailability is a significant challenge in pharmaceutical research. A higher bioavailability can reduce both the applied dosage and the side effects for the patient. One method of increasing the bioavailability is to reduce the particle size of the drug down to the nanoscale. An innovative procedure for the preparation of particles in the submicron size range is spray drying with aerosol conditioning, followed by subsequent separation of the particles in an electrostatic precipitator (ESP). This process has been tested before in an earlier work with aqueous model substances at high production rates (1 g/h) and narrow particle-size distributions (mannitol: d = 455 nm, span = 0,8) in the submicron range. Spray drying from an aqueous solution with low drug concentrations (<1 wt-%) leads to particles in the lower nanosize range, but the low concentrations make this process inefficient. A custom-made plant was modified in order to handle the organic spray-drying process. In addition, explosion protection had to be considered. This work focuses on the spray drying of submicron particles from organic solvents for the purpose of increasing the dissolution rate of the API griseofulvin. API particles were successfully produced in the submicron size-range, characterized and the dissolution behavior was investigated. The dissolution time to dissolve 80% of the drug, t, was reduced from 21.5 min for the micronized grade API to 8.5 min for the submicron product.
将水溶性差的活性药物成分（API）制成具有足够生物利用度的制剂是药物研究中的一个重大挑战。更高的生物利用度可以降低患者的用药剂量和副作用。提高生物利用度的一种方法是将药物的粒径减小到纳米级。一种用于制备亚微米粒径范围内颗粒的创新方法是喷雾干燥与气溶胶调节相结合，然后在静电除尘器（ESP）中对颗粒进行后续分离。在早期的工作中，已经使用高生产速率（1g/h）和窄粒径分布（甘露醇：d=455nm，span=0.8）的水性模型物质对该工艺进行了测试。从低药物浓度（<1wt-%）的水溶液中喷雾干燥会导致粒径处于较低的纳米范围内，但低浓度会降低该工艺的效率。为了处理有机喷雾干燥过程，对定制工厂进行了修改。此外，还必须考虑防爆问题。这项工作的重点是从有机溶剂中喷雾干燥亚微米颗粒，以提高 API 灰黄霉素的溶解速率。成功地在亚微米范围内制备了 API 颗粒，并对其进行了表征和溶解行为的研究。与微米级 API 相比，80%药物溶解时间 t 从 21.5 分钟缩短到 8.5 分钟。
