title: Correlation of inhibitory effects of polymers on indomethacin precipitation in solution and amorphous solid crystallization based on molecular interaction.
abstract: OBJECTIVE
  To correlate the polymer's degree of precipitation inhibition of indomethacin in solution to the amorphous stabilization in solid state.
  
  
  METHODS
  Precipitation of indomethacin (IMC) in presence of polymers was continuously monitored by a UV spectrophotometer. Precipitates were characterized by PXRD, IR and SEM. Solid dispersions with different polymer to drug ratios were prepared using solvent evaporation. Crystallization of the solid dispersion was monitored using PXRD. Modulated differential scanning calorimetry (MDSC), IR, Raman and solid state NMR were used to explore the possible interactions between IMC and polymers.
  
  
  RESULTS
  PVP K90, HPMC and Eudragit E100 showed precipitation inhibitory effects in solution whereas Eudragit L100, Eudragit S100 and PEG 8000 showed no effect on IMC precipitation. The rank order of precipitation inhibitory effect on IMC was found to be PVP K90 > Eudragit E100 > HPMC. In the solid state, polymers showing precipitation inhibitory effect also exhibited amorphous stabilization of IMC with the same rank order of effectiveness. IR, Raman and solid state NMR studies showed that rank order of crystallization inhibition correlates with strength of molecular interaction between IMC and polymers.
  
  
  CONCLUSIONS
  Correlation is observed in the polymers ability to inhibit precipitation in solution and amorphous stabilization in the solid state for IMC and can be explained by the strength of drug polymer interactions.
authors.forename: Harsh
authors.initials: H
authors.lastname: Chauhan
authors.forename: Anuj
authors.initials: A
authors.lastname: Kuldipkumar
authors.forename: Timothy
authors.initials: T
authors.lastname: Barder
authors.forename: Ales
authors.initials: A
authors.lastname: Medek
authors.forename: Chong-Hui
authors.initials: CH
authors.lastname: Gu
authors.forename: Eman
authors.initials: E
authors.lastname: Atef
mesh_terms: D000179:Acrylates / Q000737:chemistry; D011232:Chemical Precipitation; D003460:Crystallization; D007213:Indomethacin / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D011109:Polymethacrylic Acids / Q000737:chemistry; D011145:Polyvinyls / Q000737:chemistry; D011759:Pyrrolidines / Q000737:chemistry; D012995:Solubility; D012996:Solutions / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry
chemical_list: D000179:Acrylates; C477020:Eudragit E100; D011108:Polymers; D011109:Polymethacrylic Acids; D011145:Polyvinyls; D011759:Pyrrolidines; D012996:Solutions; D012997:Solvents; C505150:poly(N-vinylpyrrolidine); C038300:methylmethacrylate-methacrylic acid copolymer; D011092:Polyethylene Glycols; D007213:Indomethacin