Downstream processing of irbesartan nanocrystalline suspension and mini-tablet development - Part II.

The objectives of this study were to evaluate the impact of formulation variables on the drying of nanocrystalline suspensions either via bead layering or spray granulation and develop mini-tablets from the dried nanocrystalline powders. Irbesartan (crystalline Form B), a poorly soluble drug substance was chosen as a model compound. An optimized irbesartan nanocrystalline suspension with a mean particle size of 300 nm was utilized for the downstream processing. Irbesartan nanocrystalline suspension was dried either by layering onto the microcrystalline cellulose beads (i.e. 200 or 500 µm) or by granulation (mannitol or microcrystalline cellulose as substrates) at two different drug loadings (i.e. 10% or 30% w/w). Smaller size beads layered with nanocrystals resulted in faster dissolution profiles compared to larger size beads at both the studied drug loadings (i.e. 10 and 30% w/w). Mannitol granules containing irbesartan nanocrystals resulted in faster dissolution profiles compared to microcrystalline cellulose granules. Microcrystalline cellulose beads and mannitol granules containing irbesartan nanocrystals (i.e. 30% w/w drug loading) were further compressed into mini-tablets. Mini-tablets retained fast drug dissolution characteristics of the dried powders. The results from this study indicated that the spray granulation is a superior drying approach compared to bead layering for drying of irbesartan nanocrystalline suspension and mini-tablet development.