Controlled release of Argatroban from PLA film - Effect of hydroxylesters as additives on enhancement of drug release

The aim of this study was to develop a drug eluting stent that prevents vein restenosis. For this, we selected argatroban as the study drug and poly(lactic acid) (PLA) as the matrix. To enhance the release of argatroban from PLA film, the addition of hydroxylesters (additives) was investigated. The additives investigated were diethyl tartrate (DET), diethyl malate (DEM), and triethyl citrate (TEC). Marked enhancement of drug release was observed in DET-added film, while TEC- or DEM-added film showed little enhancement. To clarify the effect of DET, the release profile based on the contents of the drug and DET in the film and the effect of alkyl chain length of tartrate were studied. Tartrates used were di-methyl, di-i-propyl, and di-n-butyl esters (DMT, DiPT, and DnBT, respectively), and the enhancement order was DMT congruent to DET >> DiPT congruent to DBT congruent to PLA alone. The reasons for enhancement were discussed from the viewpoint of drug release behavior, degradation of PLA, water uptake within the film, and SEM observations. It was concluded that enhancement of drug release was due to large amounts of water uptake within the film which resulted in the formation of open pores at its surface. (C) 2008 Wiley Periodicals, Inc.