design of experiments (DOEs)

  In this investigation, roll compaction/dry granulation (RCDG) process was optimized for formulation of model amorphous drug candidate with fine-fluffy nature and poor flowability.  Three operating parameters the roller speed, the hydraulic pressure and the granulator speed on the Alexanderwerk WP 120 Pharma Roll Compactor were varied. The planned response variable for study was % retention over #60 BSS mesh. The number of compaction cycles required to get not less than 90% retention over #60 BSS mesh were evaluated. These optimized operating parameters were used during drug granulation for formulation variable optimization. The granules obtained from process optimization study were compressed at kilogram scale using ingredients in concentration selected from formulation optimization study to evaluate for the loss in tabletability, a phenomenon commonly observed with RCDG technology. The roll compaction operating parameters that simultaneously met all constraints were roller speed 4 rpm, hydraulic pressure 70 bars and granulator speed 30 rpm with course mesh screen of 2.0 mm, fine screen of 1.0 mm and three compaction cycles. The results of the drug release profile and physico-chemical evaluation of tablets confirmed that judicious optimization of process parameters and selection of appropriate excipients could lead to successful drug formulation by RCDG technology.