title: Reduction of tablet weight variability by optimizing paddle speed in the forced feeder of a high-speed rotary tablet press.
abstract: BACKGROUND
  Tableting is a complex process due to the large number of process parameters that can be varied. Knowledge and understanding of the influence of these parameters on the final product quality is of great importance for the industry, allowing economic efficiency and parametric release.
  
  
  OBJECTIVE
  The aim of this study was to investigate the influence of paddle speeds and fill depth at different tableting speeds on the weight and weight variability of tablets.
  
  
  METHODS
  Two excipients possessing different flow behavior, microcrystalline cellulose (MCC) and dibasic calcium phosphate dihydrate (DCP), were selected as model powders. Tablets were manufactured via a high-speed rotary tablet press using design of experiments (DoE). During each experiment also the volume of powder in the forced feeder was measured.
  
  
  CONCLUSIONS
  Analysis of the DoE revealed that paddle speeds are of minor importance for tablet weight but significantly affect volume of powder inside the feeder in case of powders with excellent flowability (DCP). The opposite effect of paddle speed was observed for fairly flowing powders (MCC). Tableting speed played a role in weight and weight variability, whereas changing fill depth exclusively influenced tablet weight.
  
  
  CONCLUSIONS
  The DoE approach allowed predicting the optimum combination of process parameters leading to minimum tablet weight variability. Monte Carlo simulations allowed assessing the probability to exceed the acceptable response limits if factor settings were varied around their optimum. This multi-dimensional combination and interaction of input variables leading to response criteria with acceptable probability reflected the design space.
authors: Laboratory of Pharmaceutical Technology, Ghent University , Ghent , Belgium and.
authors: Elisabeth
authors: E
authors: Peeters
authors: Thomas
authors: T
authors: De Beer
authors: Chris
authors: C
authors: Vervaet
authors: Jean-Paul
authors: JP
authors: Remon
mesh_terms: D002130:Calcium Phosphates / Q000737:chemistry*; D002482:Cellulose / Q000737:chemistry*; D004339:Drug Compounding / Q000295:instrumentation / Q000379:methods*; D005079:Excipients / Q000737:chemistry*; D008956:Models, Chemical; D009010:Monte Carlo Method; D011208:Powders; D011786:Quality Control; D013607:Tablets; D013997:Time Factors
chemical_list: D002130:Calcium Phosphates; D005079:Excipients; D011208:Powders; D013607:Tablets; D002482:Cellulose; C494366:calcium phosphate, dibasic, dihydrate; C109691:microcrystalline cellulose
keywords: Critical process variables; design space; die filling; direct compression; flowability; forced feeder; process optimization; tableting