Size Control of Ibuprofen Microspheres with an Acrylic Polymer by Changing the pH in an Aqueous Dispersion Medium and Its Mechanism

Abstract

The size of ibuprofen microspheres fabricated by the o/w emulsion solvent diffusion method was controlled by adjusting the pH (1.0-5.0) in an aqueous dispersion phase. As the pH decreased, the diameter of the microspheres decreased, while drug entrapment efficiency and yield of microspheres remained unchanged. In the present system, the size of microspheres increased via coalescence and fusion of the oil emulsion droplets before solidification of the droplets occurred. At a lower pH, the solvent (ethanol) diffiusion rate from the oil droplets to the squeous phase was accelerated, and the drug and polymer solved in the oil droplets were rapidly deposited, forming a rigid outer-shell on the surface of the droplets to prevent the coalescence and fusion. These accelerations of solvent diffusion and rapid solidification were attributed to that the hydrogen bonding between drug and solvent, and the solubility of drug in the droplets were reduced in the strongly acidic (low pH) aqueous medium.