Use of experimental design for identifying the most important formulation and technological variables in pelletization by powder layering

The objective of this work was to identify, using a statistical experimental design, the critical process parameters that influence the pellets production by powder layering technique. A fractional factorial experimental design was used with five variables and two levels for screening the following parameters that can influence preparation of pellets: pan speed, powder application frequency, binder (polyvinylpyrrolidone) solution concentration, anti-sticking agent (talcum), wetting agent (sodium lauryl sulphate). Pellets containing indomethacin, chosen as the model drug, were prepared using a conventional coating pan. The results show that the most important variables in pellets production with the powder layering technique were: binder solution concentration, powder application frequency and pan speed. Anti-sticking agent (talcum) and wetting agent (sodium lauryl sulphate) had little influence on pellets proprieties obtained by the pan powder layering technique. Pellets with very good pharmaceutical quality (low proportion of sticked pellets, low friability and good flow properties) can be obtained in conventional coating pan via the powder layering technique with a good layering powder efficiency by using a relatively high pan speed and a high concentration of binder solution.