Influence of composition of the crystallization medium on the physical properties and mechanical behavior of adipic acid crystals.

摘要

Adipic acid (hexanedioic acid, 1,4-butanedicarboxylic acid) is a neglected pharmaceutical excipient and is primarily used in the manufacture of artificial resins, plastics (nylon) and urethane foams. Adipic acid was crystallized from aqueous solutions containing n-octanoic acid (0-0.552 mmol/L) or a cosolvent (2-propanol, acetone, dioxane, or acetonitrile at 0, 25, 50, 100% v/v). A high performance liquid chromatographic method was developed for determining the mole fraction of n-octanoic acid incorporated into the adipic acid crystals. Gas chromatography-mass spectrophotometry was used to identify the composition of the crystals obtained from water + cosolvent mixtures, while Karl Fischer titrimetry was employed to determine the water content. The changes in solid state properties, particularly those which depend on the crystal defects, crystal morphology and compactibility, were studied. Air-helium pycnometry, differential scanning calorimetry, and synchrotron X-ray Laue diffractometry, helped assess the lattice strain and the associated lattice defects. Scanning electron microscopy showed morphological changes. The compactibility of the crystals was studied using Hiestand's indices of tableting performance, ITP, which comprise strain index, SI, best case bonding index, bBI, worst case bonding index, wBI, and brittle fracture index, BFI, (Int. J. Pharm., 67, 1991, 231). A comminution technique was developed for quantifying the amount of included water in these crystals.;The crystallization of adipic acid in the presence of n-octanoic acid (;The presence of 2-propanol, acetone or dioxane in the crystallization medium causes the density of the adipic acid crystals to decrease, suggesting an increase in lattice strain, while the presence of acetonitrile causes the density to increase, suggesting an uptake of acetonitrile and/or water into interstitial spaces. The melting point of the crystals is unchanged by the cosolvents. As the amount of 2-propanol, acetone or dioxane in the crystallization medium is increased, the enthalpy and the entropy of fusion increase, suggesting a relief of lattice strain. However, with acetonitrile this behavior is reversed. The total water content and included water decrease with decrease in water activity with each cosolvent in the crystallization medium. The included water is reduced by 82% through crystallization from 25% (v/v) 2-propanol or acetone, showing specific solvent effects.