Multiple tamping effects on drug dissolution from capsules filled on a dosing-disk type automatic capsule filling machine

The effects of number of tamps and tamping force on drug dissolution from capsules filled on an instrumented dosing-disk automatic capsule filling machine (Hofliger-Karg) were studied using hydrochlorothiazide as a model, low dose, poorly soluble drug. Generally, there was a trend toward slower dissolution rate with increasing numbers of tamps, the effect being most marked when insoluble dicalcium phosphate dihydrate was the filler. Higher compression forces improved drug release when anhydrous lactose was the filler, but adversely affected the dicalcium phosphate-based capsules. Inclusion of 4% croscarmellose sodium disintegrant tended to nullify the effects of number of tamps or tamping force with both fillers; however, the disintegrant also markedly enhanced drug dissolution from the dicalcium phosphate-based formulation. Hydrochlorothiazide dissolution from the latter formulation without disintegrant appeared to follow a "diffusion from insoluble matrix" model regardless of number of tamps or their intensity. Mercury intrusion pore size distribution data for some plugs suggested that for tamps of equal force (100 or 200 N), further powder consolidation after two tamps does not occur.