pH-triggered drug release from biodegradable microwells for oral drug delivery

Microwells fabricated from poly-L-lactic acid (PLLA) were evaluated for their application as an oral drug delivery system using the amorphous sodium salt of furosemide (ASSF) as a model drug. Hot embossing of PLLA resulted in fabrication of microwells with an inner diameter of 240 mu m and a height of 100 mu m. The microwells were filled with ASSF using a modified screen printing technique, followed by coating of the microwell cavities with a gastroresistant lid of Eudragit (R) L100. The release behavior of ASSF from the coated microwells was investigated using a mu-Diss profiler and a UV imaging system, and under conditions simulating the changing environment of the gastrointestinal tract. Biorelevant gastric medium (pH 1.6) was employed, after which a change to biorelevant intestinal release medium (pH 6.5) was carried out. Both mu-Diss profiler and UV imaging release experiments showed that sealing of microwell cavities with an Eudragit (R) layer prevented drug release in biorelevant gastric medium. An immediate release of the ASSF from coated microwells was observed in the intestinal medium. This pH-triggered release behavior demonstrates the future potential of PLLA microwells as a site-specific oral drug delivery system.