Differential Scanning Calorimetry of Chloramphenicol Palmitate and the Phase-Transitional Behavior of Chloramphenicol Palmitate observed during the Preparation of Its Oral Suspension

Abstract

Differential scanning calorimetry was carried out to elucidate the properties of two metastable forms of chloramphenicol palmitate (δ form and sub-α form) and the occurrence and the role of the sub-α form during manufacturing of chloramphenicol palmitate oral suspension. The δ form, a new form, was obtained when the small amount of melted chloramphenicol palmitate was cooled very rapidly to below 0° and it was converted to the sub-α form at 23° on heating. The X-ray diffraction pattern of the δ form was distinguished from that of any other forms reported. The other form, sub-α, was obtained by warming the δ form or directly from the melt by rapid cooling. It was transformed to the α form while liberating heat from about 40° through about 75°. The X-ray diffraction pattern, infrared absorption spectra, the behavior in the hot stage of the polarizing microscope and the differential scanning calorimetric curves suggested that the sub-α form is composed of the crystallites of the α form. Estimated thermodynamic values at the 95% confidence limit were ; ΔH_{melt→sub-α}=-9.2±0.2kcal/mole, ΔH_melt→δ=-2.8±0.5 kcal/mole, ΔH_δ→sub-a=-2.2±0.7 kcal/mole, and ΔH_sub-α→α=-2.0±0.3 (the sub-α form directly form the melt) and -6.1±0.9 kcal/mole (the sub-α form via the δ form). The supercooled dispersion of chloramphenicol palmitate in the emulsifier solution turned into the suspension while stirring. The first solid state of the chloramphenicol palmitate was estimated to be the sub-α form and it was transformed to the α-form gradually.