Oily Suspension of Micronized Crystalline Lutein for the Improvement of Dissolution and Oral Bioavailability

The present study aimed to develop an oily suspension of micronized crystalline lutein (LT) for the improvement of dissolution and oral absorption properties. The oily suspension of micronized LT (mLTS) was prepared using a wet-jet milling technique using safflower oil as a dispersant and stabilizer of LT. LT samples were physicochemically characterized in terms of appearance, crystallinity, particle size, photochemical properties, and dissolution behavior. After the oral administration of LT samples (100 mg of LT/kg) to rats, plasma concentrations of LT were monitored to evaluate the absorbability. The mean particle size of LT particles in mLTS was 10.8 μm with a span factor of 1.1, indicating the uniform size distribution of micronized LT particles. The micronized LT remained in a crystalline state even after the milling process and had a different melting point and X-ray diffractogram from LT crystals in a commercially available oily suspension of LT (LTS), suggesting a polymorphic conversion during the micronization process. After irradiation with simulated sunlight (250 W/m², 1 h), LT solution and crystalline LT showed significant degradation of LT, whereas there was no significant degradation in mLTS or LTS, possibly due to the antioxidant components in the safflower oil. In the dissolution test, mLTS demonstrated improved and gradual dissolution of LT with zero-order release kinetics. Orally dosed mLTS resulted in a significant improvement of oral bioavailability, as evidenced by being 4.1-fold higher than that of LTS. From these findings, it can be deduced that mLTS might be a promising dosage option to enhance the nutraceutical functions of LT due to the synergistic effect by particle size reduction and polymorphic conversion.