title: Correlating bilayer tablet delamination tendencies to micro-environmental thermodynamic conditions during pan coating.
abstract: OBJECTIVE
  The objective of this study was to determine the impact that the micro-environment, as measured by PyroButton data loggers, experienced by tablets during the pan coating unit operation had on the layer adhesion of bilayer tablets in open storage conditions.
  
  
  METHODS
  A full factorial design of experiments (DOE) with three center points was conducted to study the impact of final tablet hardness, film coating spray rate and film coating exhaust temperature on the delamination tendencies of bilayer tablets. PyroButton data loggers were placed (fixed) at various locations in a pan coater and were also allowed to freely move with the tablet bed to measure the micro-environmental temperature and humidity conditions of the tablet bed.
  
  
  RESULTS
  The variance in the measured micro-environment via PyroButton data loggers accounted for 75% of the variance in the delamination tendencies of bilayer tablets on storage (R(2 )= 0.75). A survival analysis suggested that tablet hardness and coating spray rate significantly impacted the delamination tendencies of the bilayer tablets under open storage conditions. The coating exhaust temperature did not show good correlation with the tablets' propensity to crack indicating that it was not representative of the coating micro-environment. Models created using data obtained from the PyroButton data loggers outperformed models created using primary DOE factors in the prediction of bilayer tablet strength, especially upon equipment or scale transfers.
  
  
  CONCLUSIONS
  The coating micro-environment experienced by tablets during the pan coating unit operation significantly impacts the strength of the bilayer interface of tablets on storage.
authors: Drug Product Science and Technology, Bristol-Myers Squibb , New Brunswick, NJ , USA.
authors: Brian M
authors: BM
authors: Zacour
authors: Preetanshu
authors: P
authors: Pandey
authors: Ganeshkumar
authors: G
authors: Subramanian
authors: Julia Z
authors: JZ
authors: Gao
authors: Faranak
authors: F
authors: Nikfar
mesh_terms: D004338:Drug Combinations; D004339:Drug Compounding / Q000379:methods* / Q000592:standards; D004355:Drug Stability; D004356:Drug Storage; D005079:Excipients / Q000737:chemistry; D006244:Hardness; D008956:Models, Chemical; D013607:Tablets / Q000737:chemistry* / Q000592:standards*; D013816:Thermodynamics
chemical_list: D004338:Drug Combinations; D005079:Excipients; D013607:Tablets
keywords: Bilayer; PyroButton data loggers; delamination; micro-environmental humidity, micro-environmental temperature; pan coating; tablet-bed humidity; tablet-bed temperature