title: Investigation of physical properties and stability of indomethacin-cimetidine and naproxen-cimetidine co-amorphous systems prepared by quench cooling, coprecipitation and ball milling.
abstract: OBJECTIVE
  The objective was to characterize the structural behaviour of indomethacin-cimetidine and naproxen-cimetidine co-amorphous systems (1 : 1 molar ratio) prepared by quench cooling, co-evaporation and ball milling.
  
  
  METHODS
  Powder X-ray diffraction (PXRD) and DSC were used to characterise the samples. Structural relaxation (i.e. molecular mobility) behaviour was obtained from the Kohlrausch-Williams-Watts (KWW) relationship.
  
  
  RESULTS
  A glass transition temperature (Tg ), on average 20 °C higher than the predicted Tg (calculated from the Fox equation), was observed in all samples. The structural relaxation was dependent on the preparative methods. At a storage temperature of 40 °C, a comparatively higher molecular mobility was observed in indomethacin-cimetidine samples prepared by ball milling (ln τ(β) = 0.8), while similar molecular mobility was found for the same sample prepared by quench cooling (ln τ(β) = 2.4) and co-evaporation (ln τ(β) = 2.5). In contrast, molecular mobility of the naproxen-cimetidine samples followed the order co-evaporation (ln τ(β) = 0.8), quench cooling (ln τ(β) = 1.6) and ball milling (ln τ(β) = 1.8).
  
  
  CONCLUSIONS
  The estimated relaxation times by the DSC-KWW method suggest that different preparative methods resulted in a variation of structural characteristics. Despite the differences in molecular mobility, all sample remained co-amorphous for up to 7 months.
authors.affiliation: School of Pharmacy, International Medical University, Bukit Jalil, Kuala Lumpur, Malaysia.
authors.forename: Ai Wei
authors.initials: AW
authors.lastname: Lim
authors.affiliation: Department of Pharmacy, University of Copenhagen, København, Denmark.
authors.forename: Korbinian
authors.initials: K
authors.lastname: Löbmann
authors.affiliation: Department of Pharmacy, University of Copenhagen, København, Denmark.
authors.forename: Holger
authors.initials: H
authors.lastname: Grohganz
authors.affiliation: Department of Pharmacy, University of Copenhagen, København, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Rades
authors.affiliation: School of Pharmacy, International Medical University, Bukit Jalil, Kuala Lumpur, Malaysia.
authors.forename: Norman
authors.initials: N
authors.lastname: Chieng
mesh_terms: D002152:Calorimetry, Differential Scanning / Q000379:methods; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002927:Cimetidine / Q000737:chemistry*; D003460:Crystallization / Q000379:methods; D004355:Drug Stability; D007213:Indomethacin / Q000737:chemistry*; D009288:Naproxen / Q000737:chemistry*; D011208:Powders / Q000737:chemistry; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D013678:Technology, Pharmaceutical / Q000379:methods; D013696:Temperature; D044366:Transition Temperature; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D011208:Powders; D009288:Naproxen; D002927:Cimetidine; D007213:Indomethacin
keywords: ball milling; co-amorphous systems; coprecipitation; differential scanning calorimetry; quench cooling; structural relaxation