Pharmacy Discipline, School of Clinical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, QLD, Australia.
School of Chemistry and Physics, Science and Engineering Faculty, Queensland University of Technology, Brisbane, QLD, Australia.
AAPS PharmSciTech. 2022 Dec 15;24(1):16. doi: 10.1208/s12249-022-02480-w.
This study investigated a systematic approach for producing ibuprofen (IBF) particles with leucine by wet milling. Using a high shear homogenizer, the particles size of the IBF was reduced. Prepared IBF microparticles were freeze-dried and characterized by using Mastersizer, SEM, DSC, XRD, ATR-FTIR, and TGA. The drug saturation solubility and in-vitro dissolution performance were carried out in phosphate buffer solution (PBS, pH 7.4) at 37°C temperature and IBF were determined using a validated HPLC method. The wet-milled method reduced the particle size from 71.3 to 1.7 μm. The minimum particle size of IBF was obtained in 0.05% Tween 80 solution homogenized at 17,000 rpm for 15 min. The saturated solubility (168.7 µg/mL) of the micronized IBF particles with leucine showed higher compared to that of the original IBF (147.4 µg/mL) in PBS solution. The prepared IBF particles containing 2.5-6.25% leucine showed significantly higher IBF release (100%) compared to that of original drug particles (55.9%) in 120 min. The excipient leucine played a major role in enhancing the solubility and dissolution profile of the prepared IBF particles probably by the formation of hydrogen bonding. The developed wet milling was an efficient and robust technique for reducing the particle size of IBF and could be a useful method for manufacturing drug particles with enhanced solubility and dissolution.
本研究采用湿磨法制备了载有亮氨酸的布洛芬（IBF）颗粒。使用高剪切匀浆机减小了 IBF 的粒径。将制备的 IBF 微粉冷冻干燥，并使用 Mastersizer、SEM、DSC、XRD、ATR-FTIR 和 TGA 进行了表征。在 37°C 的磷酸盐缓冲溶液（PBS，pH7.4）中进行了药物饱和溶解度和体外溶出性能的测定，采用经验证的 HPLC 方法测定 IBF 的含量。湿磨法使粒径从 71.3μm 减小至 1.7μm。在 17000rpm 下用 0.05%吐温 80 溶液均质 15min 可得到 IBF 的最小粒径。载有亮氨酸的微米化 IBF 颗粒的饱和溶解度（168.7µg/mL）比 PBS 溶液中原 IBF 的饱和溶解度（147.4µg/mL）高。含有 2.5-6.25%亮氨酸的制备的 IBF 颗粒在 120min 内的 IBF 释放率（100%）明显高于原药颗粒（55.9%）。赋形剂亮氨酸可能通过形成氢键，在提高制备的 IBF 颗粒的溶解度和溶解特性方面发挥了主要作用。所开发的湿磨法是一种减小 IBF 粒径的有效且稳健的技术，可能是制造具有增强的溶解度和溶解特性的药物颗粒的有用方法。
