Controlled release cyclosporine-containing biodegradable microspheres and microspheres

摘要

A controlled release pharmaceutical formulation which comprises cyclosporin entrapped in a biodegradable polymer to form microspheres or nanospheres such that the cyclosporin is substantially in an amorphous state and the biodegradable polymer comprises greater than 12.5% w/w poly(lactide). The biodegradable polymer is suitably poly-D,L-lactide or a blend of poly-D,L-lactide and poly-D,L-lactide-co-glycolide. Additionally, an enteric coating can be applied to the microspheres or nanospheres or to the oral dosage form incorporating the microspheres or nanospheres to protect the formulation while it passes through the stomach. A particularly suitable formulation comprises 50% w/w cyclosporin-loaded 80:20 blend of poly-D,L-lactide-co-glycolide to poly-D,L-lactide micro- and/or nanospheres. This formulation has the combined properties of nearly complete but relatively slow release of cyclosporin within 8 hours and is useful for targeting cyclosporin to the small intestine when administered orally.