Solid state characterization of chloramphenicol palmitate. Raman spectroscopy applied to pharmaceutical polymorphs

A pharmaceutical active compound, chloramphenicol palmitate, appears in three polymorphic forms, that can be observed at room temperature. The stable form A (biologically inactive modification), the meta-stable form B (active modification) and unstable form C were found to have distinct Raman spectra, with bands attributable to the different polymorphs. The use of hot-stage Raman microscopy (the direct coupling of Raman microscopy and hot-stage) is demonstrated for the drug substance chloramphenicol palmitate form C. All modifications of form C were produced and identified by hot-stage Raman microscopy. A close correlation of thermal and spectroscopic information was achieved by this combination of techniques. As reported in several pharmacopoeias, the content of form A should be less than 10%; therefore, a mixture of 10% (w/w) A in B was prepared, and the presence of the characteristic bands of form A after subtraction of the pure B was revealed. Moreover, mixtures between 2 and 12% (w/w) A in B were investigated and the intensity ratio (as peak area) I413-435/I1035-1158 as a function of A percentage has been demonstrated to show a linear trend. Other methods for the characterization of polymorphs were used: Fourier transform infrared spectroscopy (FT-IR), Diffuse reflectance infrared Fourier transform spectroscopy (DRIFT), Differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD). (c) 2005 Elsevier B.V. All rights reserved.