Modification of adipic acid crystals: influence of growth in the presence of fatty acid additives on crystal properties

When adipic acid is crystallized from water in the presence of a low concentration of an n-alkanoic acid, the additive is incorporated into the crystals and the crystal habit is changed. The following properties of harvested crystals grown in the presence of various concentrations of hexanoic (C6), octanoic (C8) or undecanoic acid (C11) were studied: dissolution rate (DR) and enthalpy of solution (ΔHs) in water, enthalpy of fusion (ΔHf), melting point (Tm), density (d), specific surface area (A) and scanning electron microscopy (SEM). Increasing concentrations of C6 (0–5380 μmol·dm-3) or C11 (0–67.1 μmol·dm-3) caused increasing uptake of additive and pitting of the crystal surface under SEM, while DR and A of a defined sieve fraction increased and then decreased, whereas ΔHs and ΔHf decreased to minima and then increased. In general, the changes in Tm and entropy of fusion (ΔSf) paralleled the changes in ΔHf. C6 caused negligible changes in d, whereas C11 significantly reduced d suggesting lattice expansion (0–0.8%). Various sieve fractions covering the range < 75 μ m to 850 μm showed negligible differences in ΔHf, ΔHs, Tm and d. C8 (0–139 μ mol · dm−3) elicited behaviour similar to that produced by C6 and C11, except that it reduced DR and increased d (< 0.8%). X-Ray powder diffraction of all crystalline samples failed to detect any changes in lattice dimensions (< 0.5%). Overall, DR did not exactly parallel A or SEM on the one hand nor ΔHf, ΔHs, Tm or d on the other hand, implying that DR depends on both the surface and bulk properties of the modified crystals. The results suggest that growth of drug crystals in the presence of low concentrations of non-toxic additives can be used to control dissolution rate and crystal energy.