Physically Optimized Nano-Lipid Carriers Augment Raloxifene and Vitamin D Oral Bioavailability in Healthy Humans for Management of Osteoporosis

Abstract

Raloxifene hydrochloride (RLX) is a selective estrogen receptor modulator and Vitamin D (Vit.D) is an important fat-soluble vitamin usually administrated concurrently to treat postmenopausal osteoporosis. Both drugs have low bioavailability due to absorption problems associated with low solubility. The aim of this research was to combine the 2 drugs in nanostructure lipid carriers (NLCs) in order to overcome the previously mentioned drawbacks. Face centered central composite design combined with relative weight-based desirability index was used to optimize RLX-Vit.D-NLCs and investigate the effect of independent variables on NLCs size, entrapment, dissolution, and permeation efficiencies. Pharmacokinetic parameters of optimized NLCs were tested in healthy human volunteers. The results showed that NLCs obtained at 9.37:1 lipid/drug ratio, 1.35:4 Sefsol 218/Glyceryl monostearate ratio and 2.25% Cremophor were 98 nm bearing 82.7% and 57.3% of RLX, and Vit.D, respectively. These nanocarriers enhanced RLX bioavailability by 385.6% relative to commercial product. The level of Vit.D metabolite was significantly increased from an average baseline level of 91 ± 29 nmol/L to 174 ± 36 nmol/L. High level correlation was found between fractions of RLX absorbed and dissolved. Significant improvement of RLX and Vit.D bioavailability through encapsulation within NLCs encourages its use in the treatment of postmenopausal osteoporosis compared to commercialized products.

Keywords: factorial design; in vitro in vivo correlation; nanostructure lipid carrier; postmenopausal osteoporosis.