EFFECT OF COSOLVENTS ON WATER-CONTENT AND PHYSICAL-PROPERTIES OF ACETAMINOPHEN CRYSTALLIZED FROM AQUEOUS-SOLUTIONS

This study investigated the effect of the presence of cosolvents in th e crystallization medium on the water content thermodynamic propel-tie s and physical characteristics of acetaminophen crystals as a trial to produce crystals of improved compressibility and tableting characteri stics. Acetaminophen was crystallized from aqueous solutions containin g acetone, isopropanol or dioxane at 0, 25, 50 or 100% v/v. The dried crystals were investigated for water content by Karl Fisher titrimetry , thermodynamic properties by differential scanning calorimetry the mo rphology of crystals by electron scanning microscopy and powder X-ray diffraction with an X-ray diffractometer. High yields of crystals (82 to 100% w/w) were obtained from mast crystallization media. The water content was minimum in the crystals harvested from pure acetone, isopr opanol and dioxane, and rose with increasing water ratio in the crysta llization medium. Water content decreased in the following order: acet one > isopropanol > dioxane >> water. The entropy of fusion (Delta fus S) of acetaminophen crystals decreased with increasing crystal water content, implying a parallel between the water content and the lattice strain independent of the organic solvent acetone or dioxane. Most of the crystals harvested from different crystallization media were hexa gonal prisms. Both differential scanning calorimetry and X-ray diffrac tion results showed no evidence of polymorphism.