Ketorolac-Loaded PLGA-/PLA-Based Microparticles Stabilized by Hyaluronic Acid: Effects of Formulation Composition and Emulsification Technique on Particle Characteristics and Drug Release Behaviors.

Abstract

This study aimed to develop ketorolac microparticles stabilized by hyaluronic acid based on poly(lactide-co-glycolide) (PLGA), poly(lactide) (PLA), and their blend for further application in osteoarthritis. The polymer blend may provide tailored drug release and improved physicochemical characteristics. The microparticles were prepared by water-in-oil-in-water (w/o/w) double emulsion solvent evaporation using two emulsification techniques, probe sonication (PS) and high-speed stirring (HSS), to obtain the microparticles in different size ranges. The results revealed that the polymer composition and emulsification technique influenced the ketorolac microparticle characteristics. The PS technique provided significantly at least 20 times smaller average size (1.3-2.2 µm) and broader size distribution (1.5-8.5) than HSS (45.5-67.4 µm and 1.0-1.4, respectively). The encapsulation efficiency was influenced by the polymer composition and the emulsification technique, especially in the PLA microparticles. The DSC and XRD results suggested that the drug was compatible with and molecularly dissolved in the polymer matrix. Furthermore, most of the drug molecules existed in an amorphous form, and some in any crystalline form. All of the microparticles had biphasic drug release composed of the burst release within the first 2 h and the sustained release over 35 days. The obtained microparticles showed promise for further use in the treatment of osteoarthritis.