Formulation of epichlorohydrin cross-linked starch microspheres

The present work describes a water/oil emulsion technique for the production of microspheres by cross-linking soluble starch with epichlorohyrin, which is a very efficient divalent cross-linking agent for starch. Because they are important features for potential applications, such as pulmonary administration, special attention has been paid to control the mean particle size and size distribution. Microspheres ranging from 0.3-250 mum with narrow size distributions could be obtained. Due to the strongly basic nature of the aqueous phase, no stable emulsions could be obtained in the water/oil emulsion domains. In this context, the stirring rate during the emulsification step was crucial for controlling the particle size. Additionally, a high organic-to-aqueous phase ratio and the presence of a surfactant agent helped to prevent the coalescence of the droplets during the formation of the microspheres. The process was not sensitive to modifications of the chemical conditions, such as the cross-linking ratio, which allows variation of the chemical nature of the polymer forming the core of the microspheres without modifying their morphological characteristics.