Formulation optimization and in vitro characterization of granisetron-loaded polylactic-co-glycolic acid microspheres prepared by a dropping-in-liquid emulsification technique

Abstract

Purpose: Traditional dosage forms of granisetron (GRN) decrease patient compliance associated with repeated drug administration because of the short half-life of the drug. Methods: In this study, novel GRN-loaded polylactic-co-glycolic acid (PLGA) sustained release microspheres were prepared for the first time via a dropping-in-liquid emulsification technique. The effect of various factors, such as pH of the outer phase, Tween80, polyvinyl alcohol (PVA) concentrations, and hardening process, on the encapsulation efficiency (EE), drug loading (DL), and particle size of microspheres were extensively studied. The physicochemical properties, including drug release, surface morphology, crystallinity, thermal changes, and molecular interactions, were also studied. Results: GRN has a pH-dependent solubility and showed a remarkably high solubility under an acidic condition. The EE of the alkaline medium (pH 8) was higher than that of the acidic medium (pH 4.0). EE and DL decreased in the presence of Tween80 in the outer phase, whereas EE significantly increased during hardening. The particle size of microspheres was not affected by PVA and Tween80 concentrations, but it was influenced by PVA volume and hardening. X-ray diffraction and differential scanning calorimetry results showed that the physical state of the drug changed from a crystalline form to an amorphous form, thereby confirming that the drug was encapsulated into the PLGA matrix. Fourier transform-infrared spectroscopy confirmed that some molecular interactions occurred between the drug and the polymer. GRN-loaded PLGA microspheres showed sustained release profiles of over 90% on week 3. Conclusion: GRN-loaded PLGA microspheres with sustained release were successfully prepared, and they exhibited a relatively high EE without Tween 80 as an emulsifier and with hardening process.