Microcrystal Formulations of Etoposide

This proposal relates to the water-insoluble anticancer agent, etoposide, and the use ofMicrocrystal Technology to produce an improved intravenous formulation, an improved oral formulationwith increased bioavailability and a slow-release formulation for intramuscular or subcutaneousadministration. The Microcrystal Technology is a unique delivery system in which a fine aqueoussuspension of drug is encapsulated in phospholipids by microfluidization. The suspension is stable, doesnot precipitate readily and can be lyophilized for longer storage, requiring only saline to reconstitute itlater. The advantages of the microcrystal formulation are that it avoids toxic solubilizing agents suchas tween 80 or polysorbate (which is found in present formulations of etoposide), all components aretissue compatible, slow-release formulations are possible when i.m. or s.c. administration is used andoral bioavailability of compounds can be substantially increased. The technology has applicability toother poorly soluble anticancer agents, including taxol, taxotere and camptothecin.