Formulation of Nanoparticle Containing Everolimus Using Microfluidization and Freeze-Drying.

The aims of this study were to improve in vitro dissolution property of poorly water-soluble everolimus (EVR) for enhanced bioavailability without using organic solvents and characterize the effects of microfluidization and freeze-drying on physicochemical properties of EVR nanosuspension and nanoparticle, respectively. EVR nanosuspension was prepared using microfluidization with various types and concentrations of stabilizers. After that, it was solidified into nanoparticle using freeze-drying with various concentrations of xylitol, a cryoprotectant. The particle size, zeta potential, physical stability, and chemical stability of EVR nanosuspension and nanoparticle were measured. In vitro release of EVR nanoparticle was also measured and compared with that of physical mixture. Zero point five percent (w/w) poloxamer 407 (P407) was chosen as the stabilizer considering particle size, zeta potential, and yield of EVR nanosuspension. Freeze-drying with 1% (w/w) xylitol improved both physical and chemical stability of EVR nanoparticle. In vitro release test showed improved dissolution property compared to that of physical mixture, implying enhanced bioavailability.

In vivo gastric residence and gastroprotective effect of floating gastroretentive tablet of DA-9601, an extract of Artemisia asiatica, in beagle dogs.

OBJECTIVE: DA-9601, an extract of Artemisia asiatica containing eupatilin and jaceosidin as active compounds, has been prescribed to treat gastritis in Asia. In recent times, sustained-release, floating gastroretentive (GR) tablets of DA-9601 are available on the market. In the present study, the physical properties and in vitro drug release profile, in vivo gastric residence time, and gastroprotective effect of GR tablet were compared to those of immediate release (IR) tablets of DA-9601. METHOD: In vitro buoyancy behavior (floating lag time and duration) and release profile of eupatilin were assessed in acidic medium. The in vivo intragastric behaviors of the barium sulfate-loaded IR and GR tablets were evaluated in beagle dogs by radiographic studies. Local gastroprotective effect was compared in an experimentally induced gastric lesion in beagle dogs after oral administration of IR (three times per day) or GR (twice daily) tablets for 15 days. RESULTS: Upon contact with gastric juice, a low-density floating tablet (apparent density of 0.93 g/cm(3)) was buoyant on the medium and was upheld for 14 hours, providing sustained drug release profile, whereas the IR tablet disintegrated within 10 minutes, showing complete drug release within 2 hours. In vivo radiographic studies showed that the GR tablet was retained for >4 hours in the stomach. Both DA-9601 formulations remarkably alleviated gastric mucosal injury compared to placebo group, when observed by gastric endoscopy. CONCLUSION: Twice-daily GR tablets exhibited a prolonged gastric residence time and a remarkable mucosal restoration effect in animal models. Therefore, the GR system of DA-9601 could be a substitute dosage form for the treatment of gastritis, while reducing the dosing frequency and thus improving patient compliance.