title: Powder X-ray diffraction method for the quantification of cocrystals in the crystallization mixture.
abstract: BACKGROUND
  The solid state purity of cocrystals critically affects their performance. Thus, it is important to accurately quantify the purity of cocrystals in the final crystallization product.
  
  
  OBJECTIVE
  The aim of this study was to develop a powder X-ray diffraction (PXRD) quantification method for investigating the purity of cocrystals. The method developed was employed to study the formation of indomethacin-saccharin (IND-SAC) cocrystals by mechanochemical methods.
  
  
  METHODS
  Pure IND-SAC cocrystals were geometrically mixed with 1:1 w/w mixture of indomethacin/saccharin in various proportions. An accurately measured amount (550 mg) of the mixture was used for the PXRD measurements. The most intense, non-overlapping, characteristic diffraction peak of IND-SAC was used to construct the calibration curve in the range 0-100% (w/w). This calibration model was validated and used to monitor the formation of IND-SAC cocrystals by liquid-assisted grinding (LAG).
  
  
  RESULTS
  The IND-SAC cocrystal calibration curve showed excellent linearity (R(2) = 0.9996) over the entire concentration range, displaying limit of detection (LOD) and limit of quantification (LOQ) values of 1.23% (w/w) and 3.74% (w/w), respectively. Validation results showed excellent correlations between actual and predicted concentrations of IND-SAC cocrystals (R(2) = 0.9981).
  
  
  CONCLUSIONS
  The accuracy and reliability of the PXRD quantification method depend on the methods of sample preparation and handling. The crystallinity of the IND-SAC cocrystals was higher when larger amounts of methanol were used in the LAG method.
  
  
  CONCLUSIONS
  The PXRD quantification method is suitable and reliable for verifying the purity of cocrystals in the final crystallization product.
authors.affiliation: Department of Health Sciences, Luleå University of Technology, Sweden.
authors.forename: Luis
authors.initials: L
authors.lastname: Padrela
authors.forename: Edmundo Gomes
authors.initials: EG
authors.lastname: de Azevedo
authors.forename: Sitaram P
authors.initials: SP
authors.lastname: Velaga
mesh_terms: D002138:Calibration; D002152:Calorimetry, Differential Scanning / Q000379:methods; D003460:Crystallization; D007213:Indomethacin / Q000737:chemistry*; D011208:Powders / Q000737:chemistry*; D015203:Reproducibility of Results; D012439:Saccharin / Q000737:chemistry*; D014961:X-Ray Diffraction / Q000379:methods*
chemical_list: D011208:Powders; D012439:Saccharin; D007213:Indomethacin