title: Physical properties of solid molecular dispersions of indomethacin with poly(vinylpyrrolidone) and poly(vinylpyrrolidone-co-vinyl-acetate) in relation to indomethacin crystallization.
abstract: OBJECTIVE
  To measure solid-state features of amorphous molecular dispersions of indomethacin and various molecular weight grades of poly(vinylpyrrolidone), PVP, and poly(vinylpyrrolidone-co-vinylacetate), PVP/VA, in relation to isothermal crystallization of indomethacin at 30 degrees C.
  
  
  METHODS
  The glass transition temperatures (Tg) of molecular dispersions were measured using differential scanning calorimetry (DSC). FT-IR spectroscopy was used to investigate possible differences in interactions between indomethacin and polymer in the various dispersions. The enthalpy relaxation of 5%w/w and 30%w/w polymer dispersions was determined following various aging times. Quantitative isothermal crystallization studies were carried out with pure indomethacin and 5%w/w polymers in drug as physical mixtures and molecular dispersions.
  
  
  RESULTS
  All coprecipitated mixtures exhibited a single glass transition temperature. All polymers interacted with indomethacin in the solid state through hydrogen bonding and in the process eliminated the hydrogen bonding associated with the carboxylic acid dimers of indomethacin. Molecular mobility at 16.5 degrees C below Tg was reduced relative to indomethacin alone, at the 5%w/w and 30%w/w polymer level. No crystallization of indomethacin at 30 degrees C was observed in any of the 5%w/w polymer molecular dispersions over a period of 20 weeks. Indomethacin alone and in physical mixtures with various polymers completely crystallized to the y form at this level within 2 weeks.
  
  
  CONCLUSIONS
  The major basis for crystal inhibition of indomethacin at 30 degrees C at the 5%w/w polymer level in molecular dispersions is not related to polymer molecular weight and to the glass transition temperature, and is more likely related to the ability to hydrogen bond with indomethacin and to inhibit the formation of carboxylic acid dimers that are required for nucleation and growth to the gamma crystal form of indomethacin.
authors.affiliation: School of Pharmacy, University of Wisconsin-Madison, 53706, USA.
authors.forename: T
authors.initials: T
authors.lastname: Matsumoto
authors.forename: G
authors.initials: G
authors.lastname: Zografi
mesh_terms: D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D003720:Densitometry; D007213:Indomethacin / Q000737:chemistry*; D008970:Molecular Weight; D011205:Povidone / Q000737:chemistry*; D011759:Pyrrolidines / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D013696:Temperature; D013997:Time Factors; D014753:Vinyl Compounds / Q000737:chemistry*; D014961:X-Ray Diffraction
chemical_list: D011759:Pyrrolidines; D014753:Vinyl Compounds; C402301:poly(vinylpyrrolidone-co-vinyl-acetate); D011205:Povidone; D007213:Indomethacin