SMALL DRUG SAMPLE FABRICATION OF CONTROLLED-RELEASE POLYMERS USING THE MICROEXTRUSION METHOD

Ethylene vinylacetate polymer (EVA) has been used for many years to fa bricate controlled-release polymeric implant devices with which drugs of high or low molecular weight compounds could be delivered with zero -order kinetics. However, because the known fabrication methods such a s solvent evaporation, casting and possible shrinkage are not sufficie ntly controllable we have now developed the microextrusion method with which even small amount of clinically important and expensive drugs c an be incorporated into EVA with high reproducibility. We show here th at devices produced by the microextrusion method allows for a controll ed delivery of several neurotoxic and neurotherapeutic compounds such as alpha-methyl-p-tyrosine, diazepam, quinolinic acid, and phencyclidi ne. Each substance is slowly released from the polymer, as evidenced b y spectrophotometric data, for up to 120 days at daily rates varying f rom 18.4 mu g of phencyclidine to 97.6 mu g/day of diazepam. Thus, mic roextrusion is a valuable method for fabricating controlled-release po lymers in which small amounts of scarce drugs can be incorporated. Ano ther advantage of the current procedure is that polymers can be fabric ated with very little amount of solvent. (C) 1998 Elsevier Science B.V . All rights reserved.