No abstract

Treating X-ray amorphous powder patterns with different solid-state models, ranging from disordered nanocrystalline to glassy and amorphous, resulted in the assignment of structures in each of the systems examined. The pharmaceutical implications with respect to the stability of the solid are discussed.

The present study deals with the acid-base reaction of three solid-state forms of the nonsteroidal antiinflammatory drug indomethacin with ammonia gas. X-ray powder diffraction, optical microscopy, gravimetry, and spectroscopic methods were employed to establish the extent of the reaction as well as the lattice changes of the crystal forms. The glassy amorphous form readily reacts with ammonia gas to yield a corresponding amorphous ammonium salt. In addition, the metastable crystal form of indomethacin (the alpha-form) also reacts with ammonia gas, but produces the corresponding microcrystalline ammonium salt. This reaction is anisotropic and propagates along the a-axis of the crystals. The stable crystal form (the gamma-form), however, is inert to ammonia gas. Amorphous indomethacin can react with ammonia gas because it has more molecular mobility and free volume. The reactivity differences between the alpha- and gamma-forms are dictated by the arrangement of the molecules within the respective crystal lattices. The recently determined crystal structure of the metastable alpha-form of indomethacin (monoclinic P2(1) with Z = 6, V = 2501.8 A(3), D(c) = 1.42 g.cm(-3)) has three molecules of indomethacin in the asymmetric unit. Two molecules form a mutually hydrogen-bonded carboxylic acid dimer, while the carboxylic acid of the third molecule is hydrogen bonded to one of the amide carbonyls of the dimer. The carboxylic acid groups of the alpha-form are exposed on the [100] faces and are accessible to attack by ammonia gas. After one layer of molecules reacts, the reactive groups in the subsequent layer are accessible to the ammonia gas. This process proceeds along the a-axis until the ammonia gas has penetrated the entire crystal. In contrast to the alpha-form, the gamma-form has a centrosymmetric crystal structure in which the hydrogen-bonded carboxylic acid dimers are not accessible to ammonia gas because they are caged inside a hydrophobic shield comprising the remainder of the indomethacin molecule. In view of the significantly lower density of the stable gamma-form as compared to the metastable alpha-form (1.37 and 1.42 g cm(-3), respectively), it became apparent that the reactivity of the crystal forms depends exclusively on the molecular arrangement and not on the packing density of the indomethacin crystals.

Sorption of hydrophobic organic chemicals in natural sediment suspensions was found to frequently require extended time periods (days to weeks) for complete equilibration. Sorption dynamics could be described by a two‐compartment model that distinguished rapid or “labile” exchange (requiring at most a few hours to achieve) from highly retarded or “nonlabile” sorption requiring days to weeks to occur. In general, one‐half or less of the total sorption was labile. For highly hydrophobic chemicals and high solid concentrations, the labile fraction decreased to 0.1 or less in some systems. The kinetic exchange constant for nonlabile sorption varied inversely with the sorption equilibrium constant. That is, the more highly sorbed chemicals sorbed more slowly. For some sediments, air‐drying to facilitate sample transport or storage was found to result in formation of highly stable aggregates that severely altered sorbent availability to hydrophobic chemicals. An understanding of sorption dynamics is important in describing the fate of highly sorbed pollutants in aquatic systems.