Tuning Drug Release via Twin Screw Extrusion in Polyester Films.

Laboratory investigations of polyester biomaterials overly rely on additives and solvent-casting manufacturing techniques that do not allow translation into industrial processing owing to the volatile organic compounds present. These impediments of bench to bedside translation are addressed with a "green chemistry" twin screw extrusion approach, where the extrusion parameters control the release profile. Advantages include elimination of volatile organic compounds, removal of plastic plasticizers/additives, and a low temperature production that is applicable to both academia and industry. Poly (d, l-lactide-co-glycolide) (PLGA), a labile polyester drug depot is loaded with fluorescein diacetate (FDAc), a pH/heat sensitive drug that degrades to fluorescein. Processing of FDAc suggests no degradation at elevated temperatures or high shears, indicating hydrophobic small molecules can be homogeneously dispersed with no detrimental effects. In vitro release of FDAc in physiological environments varies release profile through ratios of ester/acid-terminated PLGA without secondary additives. Postprocessing stability investigations of PLGA resin with size exclusion chromatography and differential scanning calorimetry validate no significant polymer degradation. Through judicious choice of parameters, release can be tuned from 15-250 microgram per sq. cm per day. Twin screw extrusion production of PLGA drug depots reveals a promising method of tailor-made drug delivering thin films for various pharmaceutical applications.