title: Determination of the crystallinity of cephalexin in pharmaceutical formulations by chemometrical near-infrared spectroscopy.
abstract: BACKGROUND
  Near-infrared (NIR) spectroscopy has gained wide acceptance in the pharmaceutical industry as a rapid and non destructive method for drug identification and the determination of the drug content of preparations.
  
  
  OBJECTIVE
  The crystallinity of cephalexin (CEX) in microcrystalline cellulose (MCC) was determined using a nondestructive NIR reflectance spectroscopic technique. The molecular interaction of a ground amorphous solid of CEX was investigated by the method.
  
  
  METHODS
  Six kinds of standard material with various degrees of crystallinity were prepared by the physical mixing of crystalline, amorphous CEX, and MCC. X-ray powder diffraction profiles and NIR spectra were recorded for standard samples. A chemometric analysis of the NIR spectral data sets was conducted using principal component regression (PCR).
  
  
  RESULTS
  The correlation between the actual crystallinity of CEX and that predicted using the conventional X-ray diffraction method showed a straight line with a slope of 1.000, an intercept of -2.071 × 10⁻⁵ and a correlation coefficient of determination (R²) of 0.974. The NIR spectrum of amorphous CEX showed significantly different peaks at 1176 and 1206 nm because of the CH₃ group from those of CEX. PCR was performed on various kinds of pretransformed NIR spectral data sets of standard samples of CEX. To minimize the SE of cross-validation (SECV), the spectral data sets were subjected to the leave-one-out method. The second derivative treatment in the range of 1176-1206 nm yielded the lowest SECV values. Based on a two-component model, a plot of the calibration data between the actual crystallinity of CEX and that predicted by the NIR method was obtained. The plot showed a straight line (Y = 0.995X + 0.117 and R(2) = 0.994; n = 18). The mean bias for the NIR and X-ray powder diffraction methods was calculated to be 1.52% and 2.26%, and mean accuracy was 3.06% and 7.14%, respectively.
  
  
  CONCLUSIONS
  NIR spectral changes of crystalline CEX during grinding suggested that the intermolecular hydrogen bonds between the amino and carboxyl groups are destroyed and the binding of methyl groups is heightened by the resonance effect of carboxyl groups, and the crystals are transformed into amorphous CEX.
authors: Kobe Pharmaceutical University, Motoyamakitamachi, Higashinada, Kobe, Japan.
authors: Yuya
authors: Y
authors: Fukui
authors: Makoto
authors: M
authors: Otsuka
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry; D002482:Cellulose / Q000737:chemistry*; D002506:Cephalexin / Q000737:chemistry*; D003460:Crystallization; D005079:Excipients / Q000737:chemistry*; D006860:Hydrogen Bonding; D011208:Powders; D025341:Principal Component Analysis; D019265:Spectroscopy, Near-Infrared / Q000379:methods*; D014961:X-Ray Diffraction
chemical_list: D000900:Anti-Bacterial Agents; D005079:Excipients; D011208:Powders; D002482:Cellulose; D002506:Cephalexin; C109691:microcrystalline cellulose