Controlled Release of Cyclosporine from Microspheres

Abstract

A controlled release microsphere formulation of cyclosporine is reported for the first time. Ethylene-vinyl acetate copolymer was utilized to prepare microspheres containing cyclosporine. The polymer was dissolved in methylene chloride (10% w/v) to which different quantities of cyclosporine was added to give drug loadings of 5, 25 and 50% in the microspheres. The polymer-drug solution was extruded into ethanol, where gelling of the polymer was achieved at −78°C in an ethanol-liquid nitrogen bath. Microspheres containing 25% of cyclosporine retained their shape and gave optimum results. Lower drug loadings (5% cyclosporine) resulted in deformed microspheres, whereas high drug loadings (50 % cyclosporine) produced tear drop shaped microspheres. This method used to prepare microspheres is simple, quick and inexpensive and can be used for drugs that are unstable to heat. Furthermore, the polymer used is bio-compatible and can be used to design formulations such as films containing cyclosporine which can then be used as subcutaneous implants.