Formulation of epichlorohydrin cross-linked starch microspheres

The present work describes a water/oil emulsion technique for the productio n of microspheres by cross-linking soluble starch with epichlorohyrin, whic h is a very efficient divalent cross-linking agent for starch. Because they are important features for potential applications, such as pulmonary admin istration, special attention has been paid to control the mean particle siz e and size distribution. Microspheres ranging from 0.3-250 mum with narrow size distributions could be obtained. Due to the strongly basic nature of t he aqueous phase, no stable emulsions could be obtained in the water/oil em ulsion domains. In this context, the stirring rate during the emulsificatio n step was crucial for controlling the particle size. Additionally, a high organic-to-aqueous phase ratio and the presence of a surfactant agent helpe d to prevent the coalescence of the droplets during the formation of the mi crospheres. 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.