Solubility enhancement of raloxifene hydrochloride by in situ micronization technique: physicochemical characterization and pharmacokinetic studies.

SIGNIFICANCE: Raloxifene hydrochloride (RH) treats osteoporosis in postmenopausal women. However, due to its limited bioavailability efforts have been focused on enhancing its solubility and bioavailability.

OBJECTIVE

In this study in situ micronization have been explored to improve drug solubility through reducing particle size and enhancing saturation solubility, dissolution rate, and pharmacokinetic properties.

METHODS

D-α-tocopheryl polyethylene glycol succinate (TPGS), Solotul HS15, Cremophor® CO40, and HPMC K4M were chosen as solubility enhancing agents to produce nanocrystals via the solvent change method. The study assessed particle size, saturation solubility, and drug release rate across different formulations containing various stabilizers and concentrations.

RESULTS

Nanoparticles stabilized by 0.1% TPGS depicted the smallest particle size (467.60 ± 37.89 nm), the highest drug release in 2 h (99.61 ± 6.72%) and saturation solubility (834.11 ± 16.73 µg/mL) in comparison to pure RH and other stabilizers. Nanoparticles of RH showed Cmax of 1.86 ± 1.1 µg/mL compared to the pure crystals of RH, which showed maximum serum concentration of 0.52 ± 0.68 µg/mL. The AUC0-24 was also inclined about four times more in nanoparticles compared to the pure drug while Tmax was the same in both groups.

CONCLUSIONS

The obtained results demonstrated in situ micronization technique by solvent change method was successful in improving RH bioavailability.