Powder characteristics, dissolution behavior and tableting of acetaminophen crystallized from water / cosolvent mixtures

ABSTRACT

Acetaminophen crystals harvested from water and/or cosolvent mixtures were evaluated for their powder characteristics, intrinsic dissolution rate [DR] and tableting behavior. The particle size of the crystals was dependent on the crystallization media. Crystals obtained from pure dioxane [D], isopropanol [IPA] or water possessed the smallest particle size. All the crystals provided excellent powder flowability as indicated by the low values of both angle of repose and the percentage compressibility. The crystals exhibited different IDR values and there was a correlation between either entropy of fusion [delta fus S] or water content and IDR of the crystals obtained from crystallization media containing IPA. Meanwhile, crystals obtained from acetone [A] or D containing solvents failed to exhibit this correlation. Direct compression of crystals produced tablets without capping. Tablet tensile strength increased with the decrease in water content of the crystals. Crystals obtained from the pure organic solvents produced the hardest tablets compared with that obtained from water or water/cosolvent mixtures. Crystals harvested from pure water exhibited friable tablets with the lowest tensile strength. A lack of correlation existed between delta fus S and tensile strength. Tablets prepared from crystals harvested from IPA containing solvents exhibited tensile strength which was inversely correlated with the mean particle size. Other tablets did not exhibit this compressible, highly flowable acetaminophen crystals with minimum water content could be obtained from pure A, D or IPA by controlled crystallization process