Role of the solvent-diffusion-rate modifier in a new emulsion solvent diffusion method for preparation of ketoprofen microspheres.

A new emulsion solvent diffusion method to prepare the microspheres of ketoprofen with an acrylic polymer was developed by utilizing sugar esters as solvent diffusion modifiers. The microspheres were produced via transient o/w emulsion droplets of the polymer, which was formed by the interaction of drug and water-miscible organic solvent, e.g. ethanol. The solvent consisting in oil droplets diffused into the outer aqueous medium. In the droplets, ethanol interacted with ketoprofen via hydrogen bonding between -OH group of ethanol and both -COOH and = CO groups of ketoprofen. These hydrogen bonds made ethanol solution strongly hydrophobic. The sugar ester added in the ethanol could inhibit such intermolecular interaction between ethanol and the = CO group of ketoprofen. Modulation in the binding force of ketoprofen-ethanol by the sugar ester contributed to achieving a desirable initial ethanol diffusion rate from the oil droplets for the formation of ketoprofen microspheres with high yield (> 85 per cent) and drug entrapment ratio (> 90 per cent).