Novel mesalamine-loaded beads in tablets for delayed release of drug to the colon

Abstract

Novel ‘beads-in-a-tablet’ formulations (total weight ∼ 740–780 mg) have been prepared that meet USP 31 requirements for Delayed Release of mesalamine. Several methods are presented that overcome breakage of beads during tablet compaction were explored. Bead formulations comprise a combination of extrusion and spheronization to produce a relatively high drug load (80%), followed by coating (25%) with a colonic-targeted drug release polymer (polymethacrylates, Eudragit^® S100), overcoated (3%) with hydroxypropyl methylcellulose (Opadry^®) to improve bead binding and compactability, and using 20% coat of lactose/sodium starch glycolate (Explotab^®) as binder/disintegrant/cushioning agent, thus allowing a sufficiently thick coating to be uniform and without being broken during tablet compaction. Then, the aforementioned beads were compressed into tablets at 1500 pounds of pressure containing 400 mg of mesalamine, and finally coating the compressed tablets with Surelease^® (ethylcellulose):Opadry^® = 1:0.5 ranging from 1.5–2.5% weight gain; the resulting tablets met USP 31 dissolution requirements for delayed release tablets.

Keywords::

• Delayed release
• mesalamine
• colonic delivery