title: An investigation of nifedipine miscibility in solid dispersions using Raman spectroscopy.
abstract: OBJECTIVE
  Raman spectroscopy is potentially an extremely useful tool for the understanding of drug-polymer interactions in solid dispersions. This is examined and demonstrated for the case of solid dispersions of nifedipine in a polymeric substrate.
  
  
  METHODS
  Solid dispersions consisting of nifedipine and polyvinyl caprolactam--polyvinyl acetate--polyethylene glycol graft copolymer (Soluplus®) were prepared by freeze drying, melting and solvent evaporation at drug loadings of 10, 30, 50, 70 and 90% w/w. Drug-polymer interactions in the amorphous solid dispersion were estimated by Raman spectroscopy. The correlation between the solid state stability of the drug in a solid dispersion and the extent of drug-polymer interaction was monitored by X-ray diffractometry.
  
  
  RESULTS
  The miscibility limit of nifedipine-Soluplus® was found to be 30% w/w drug loading for all preparation methods. The drug was found to interact with Soluplus®, through a hydrophilic interaction identified by infrared spectroscopy and a hydrophobic interaction which could be quantified by Raman spectroscopy. The average extent of the drug-polymer interaction in the studied amorphous samples at equivalent drug loading was similar, regardless of the preparation method. Inhomogeneities in samples prepared by melting contributed to a wider variation in drug-polymer interaction and poorer solid state stability, in terms of its crystallization tendency.
  
  
  CONCLUSIONS
  Raman spectroscopy was shown to be a useful technique in classifying miscibility levels based on the hydrophobic interaction between the drug and the polymer. Different drug loadings showed varying degrees of drug-polymer interaction, and hence variable solid state stability of the solid dispersion.
authors: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmaceutical Sciences, Chulalongkorn University, 254 Phyathai Road, Patumwan, Bangkok, 10330, Thailand.
authors: Sujinda
authors: S
authors: Keratichewanun
authors: Yasuo
authors: Y
authors: Yoshihashi
authors: Narueporn
authors: N
authors: Sutanthavibul
authors: Katsuhide
authors: K
authors: Terada
authors: Jittima
authors: J
authors: Chatchawalsaisin
mesh_terms: D002121:Calcium Channel Blockers / Q000737:chemistry*; D003460:Crystallization; D004339:Drug Compounding; D004347:Drug Interactions; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry*; D008956:Models, Chemical; D015394:Molecular Structure; D009543:Nifedipine / Q000737:chemistry*; D044367:Phase Transition; D011092:Polyethylene Glycols / Q000737:chemistry*; D011145:Polyvinyls / Q000737:chemistry*; D012995:Solubility; D013059:Spectrum Analysis, Raman
chemical_list: D002121:Calcium Channel Blockers; D005079:Excipients; D011145:Polyvinyls; C572167:polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer; D011092:Polyethylene Glycols; D009543:Nifedipine