Enhanced solubility, oral bioavailability and anti-osteoporotic effects of raloxifene HCl in ovariectomized rats by Igepal CO-890 nanomicelles

Abstract

The purpose of the present study was to enhance the bioavailability and anti-osteoporotic effects of raloxifene HCl (RH) by increasing its solubility and inhibition of the p-glycoprotein pump using surfactant micelles of Igepal CO-890. The micelles were prepared by the direct method and their critical micellar concentration, drug dissolution rate, saturated solubility, drug loading and surface morphology were defined. The cytotoxicity of Igepal CO-890 and its ability to inhibit the p-glycoprotein pump were studied on Caco-2 cells. The pharmacokinetic parameters were analyzed by oral administration of a single dose of 15 mg/kg in Wistar rats. Anti-osteoporotic effects were studied by measuring the calcium, phosphorous, and uterus weight of rats after one month of oral administration of 6 mg/kg/day of RH in ovariectomized rats. Igepal CO-890 micelles enhanced the RH solubility by about two-fold. The FT-IR and DSC studies indicated no interaction between the drug and the surfactant. XRD spectrum showed an amorphous state of RH in the micelles. The p-glycoprotein pump was inhibited by Igepal CO-890 in Caco-2 cells comparable to verapamil. Micelles increased the uterine weight and decreased the serum calcium and phosphorus significantly compared to the untreated drug. Oral bioavailability of RH increased about four-fold by nanomicelles.

Keywords:

• Raloxifene HCl
• dissolution rate
• ovariectomized rats
• p-glycoprotein pump
• surfactant micelles

Disclosure statement

The authors declare no conflict of interest.

Additional information

Funding

The authors appreciate financial support of this work by Vice Chancellery of Isfahan University of Medical Sciences.