title: The influence of API concentration on the roller compaction process: modeling and prediction of the post compacted ribbon, granule and tablet properties using multivariate data analysis.
abstract: OBJECTIVE
  While previous research has demonstrated roller compaction operating parameters strongly influence the properties of the final product, a greater emphasis might be placed on the raw material attributes of the formulation. There were two main objectives to this study. First, to assess the effects of different process variables on the properties of the obtained ribbons and downstream granules produced from the rolled compacted ribbons. Second, was to establish if models obtained with formulations of one active pharmaceutical ingredient (API) could predict the properties of similar formulations in terms of the excipients used, but with a different API.
  
  
  METHODS
  Tolmetin and acetaminophen, chosen for their different compaction properties, were roller compacted on Fitzpatrick roller compactor using the same formulation. Models created using tolmetin and tested using acetaminophen. The physical properties of the blends, ribbon, granule and tablet were characterized. Multivariate analysis using partial least squares was used to analyze all data.
  
  
  RESULTS
  Multivariate models showed that the operating parameters and raw material attributes were essential in the prediction of ribbon porosity and post-milled particle size. The post compacted ribbon and granule attributes also significantly contributed to the prediction of the tablet tensile strength.
  
  
  CONCLUSIONS
  Models derived using tolmetin could reasonably predict the ribbon porosity of a second API. After further processing, the post-milled ribbon and granules properties, rather than the physical attributes of the formulation were needed to predict downstream tablet properties. An understanding of the percolation threshold of the formulation significantly improved the predictive ability of the models.
authors.affiliation: a Department of Industrial and Physical Pharmacy and.
authors.forename: Nathan
authors.initials: N
authors.lastname: Boersen
authors.forename: M Teresa
authors.initials: MT
authors.lastname: Carvajal
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Morris
authors.forename: Garnet E
authors.initials: GE
authors.lastname: Peck
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Pinal
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004339:Drug Compounding / Q000379:methods; D005079:Excipients / Q000737:chemistry*; D016018:Least-Squares Analysis; D008956:Models, Chemical; D015999:Multivariate Analysis; D010316:Particle Size; D016062:Porosity; D013607:Tablets; D013718:Tensile Strength; D014046:Tolmetin / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D005079:Excipients; D013607:Tablets; D000082:Acetaminophen; D014046:Tolmetin
keywords: Multivariate analysis; particle size; percolation threshold; ribbon porosity; roller compaction; tablet tensile strength