O. M. M. Santos, Douglas M. Silva, Felipe T. Martins
Jul 24, 2014
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Journal
Crystal Growth & Design
Abstract
Doxycycline (DOX) is a tetracycline class drug that is used worldwide as a broad-spectrum antibiotic. Although its clinical importance and use have been known since the 1960s, only four crystal forms have been reported until now. These are doxycycline hyclate (DOX.HYC), which is a hydrochloride salt hemiethanolate-hemihydrate; its isomorphous hydrobromide, hydrochloride salt dihydrate (DOX·HCl·2H2O); and doxycycline monohydrate (DOX·H2O). Here we report the preparation of two new multicomponent molecular crystal forms of doxycycline and their crystal structure determination along with their melting temperature, aqueous solubility, and time-dependent dissolution profile. These crystal forms are a hydronitrate salt hemihydrate (DOX·HNO3·0.5H2O) and an acetic acid solvate dihydrate (DOX·HAc·2H2O). The two new doxycycline crystal forms were compared with known forms, including DOX·HCl·2H2O, the structure of which was redetermined in this work. The structural variability of the protonation patterns, tautomeris...