ABT-761 is a
5-lipoxygenase inhibitor developed for the treatment of
asthma. The present study was undertaken to evaluate different crystal forms of
ABT-761 and their impact on in vitro and in vivo performance in
capsule formulations. Two crystal forms of
ABT-761, hemihydrate and non-solvate from different sources, were characterized by thermal analysis, x-ray
powder diffraction, moisture sorption, and intrinsic dissolution studies. An in vitro test was performed to assess the effect of formulation and
drug from different sources on drug release. Crossover design was also used to evaluate oral bioavailability of
ABT-761 hemihydrate formulations in beagle dogs. Plasma concentrations of
ABT-761 were analyzed using a reverse-phase high-performance liquid chromatography (HPLC) assay. It was found that in vivo oral absorption as well as in vitro dissolution of
ABT-761 were influenced by different formulations.
Capsule formulations of
ABT-761 hemihydrate are bioequivalent to the
solution formulation in terms of extent of absorption, butformulation and the method of granulation preparation can have a major impact on the absorption rate. In conclusion, a single crystal form of
ABT-761, i.e., hemihydrate, is preferred for subsequent product development. However, exposure of the
drug to conditions that may facilitate phase transformation should be avoided.