Spray-dried raloxifene submicron particles for pulmonary delivery: Development and in vivo pharmacokinetic evaluation in rats

Raloxifene hydrochloride (RH) is a selective oestrogen receptor modulator used for the treatment of osteo-porosis. Even though 60% of an oral dose is quickly absorbed via the gastrointestinal tract, the absolute bioa-vailability 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 (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 mu m). The pharmacokinetic study in male Wistar rats demonstrated an absolute bioavailability of 47.20% after pul-monary administration of the particles. Therefore, these submicron-sized powders are promising for pulmonary RH delivery as a dry powder medicine.