Pharmaceutical Sciences Graduate Program, Faculty of Pharmacy, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
Faculty of Pharmacy, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
Int J Pharm. 2020 Jul 30;585:119429. doi: 10.1016/j.ijpharm.2020.119429. Epub 2020 May 26.
Raloxifene hydrochloride (RH) is a selective oestrogen receptor modulator used for the treatment of osteoporosis. Even though 60% of an oral dose is quickly absorbed via the gastrointestinal tract, the absolute bioavailability of RH is only 2-3% in humans due to extensive first-pass metabolism. Various approaches to improve RH bioavailability have been reported over the past few years; however, none have focused on the development of products for pulmonary administration. Therefore, in this study, submicron particles containing RH were produced for pulmonary administration with the aim to limit first-pass metabolism. Powders were produced by vibrational atomisation spray drying with a high process yield (>80%). The drug content was between 440 and 890 mg·g, and powders had a high encapsulation efficiency (>95%), mean particle size of 400-700 nm, low residual moisture (<2%) and spherical shape. These powders showed an improved drug dissolution rate compared to the raw RH material. Moreover, they presented high dose uniformity (95-100%), a high in vitro respirable fraction (>55%) and adequate mass median aerodynamic diameter for pulmonary delivery (<5 μm). The pharmacokinetic study in male Wistar rats demonstrated an absolute bioavailability of 47.20% after pulmonary administration of the particles. Therefore, these submicron-sized powders are promising for pulmonary RH delivery as a dry powder medicine.
盐酸雷洛昔芬（RH）是一种选择性雌激素受体调节剂，用于治疗骨质疏松症。尽管 60%的口服剂量通过胃肠道迅速吸收，但由于广泛的首过代谢，RH 在人体中的绝对生物利用度仅为 2-3%。过去几年已经报道了各种提高 RH 生物利用度的方法；然而，没有一种方法专注于开发用于肺部给药的产品。因此，本研究旨在通过限制首过代谢，生产用于肺部给药的 RH 亚微米颗粒。通过振动雾化喷雾干燥生产粉末，工艺收率高（>80%）。药物含量在 440-890mg·g 之间，粉末具有高包封效率（>95%）、平均粒径为 400-700nm、低残余水分（<2%）和球形。与原始 RH 材料相比，这些粉末显示出改善的药物溶解速率。此外，它们表现出高剂量均匀性（95-100%）、高体外可吸入分数（>55%）和适合肺部给药的质量中值空气动力学直径（<5μm）。雄性 Wistar 大鼠的药代动力学研究表明，肺部给药颗粒后 RH 的绝对生物利用度为 47.20%。因此，这些亚微米大小的粉末有望成为一种干粉药物，用于肺部 RH 给药。
