Analysis and Simulation of Capsule Dissolution Problem Encountered During Prodkt Scale-Up

An in vitro capsule dissolution rate problem was encountered during scale-up of cofadroxil monohydrate, a water-soluble drug product. Initial formulation development had been carried out on a Zanasi LZ-64 with a blend containing 1.0% magnesium stearate lubricant. Scale-up capsules manufactured using a Hoflinger-Karg model GFK-1500 (H&K) showed a significantly slower dissolution rate when compared to those produced on a Zanasi LZ-64. Analysis of the problem indicated that during encepsulation on the H&K capsule machine, powder was being sheared resulting in slower in vitro capsule dissolution rate.

Shear simulation studies were conducted to select the level of magnesium stearate for encapsulation on the H&K which would maintain a satisfactory in capsule dissolution rate. A 0.3% level of magnesium stearate was selected on the basis of the simulation studies. At this lubricant level, capsules have been routinely produced on the H&K with satisfactory dissolution and encapsulation characteristics.