Crystallization of a new polymorph of acetohexamide from 2-hydroxybutyl-β-cyclodextrin solution: form VI with a high aqueous solubility.

Hibah Aldawsari, Abdulmalik Altaf, Zainy M Banjar, Daisuke Iohara, Mami Nakabayashi, Makoto Anraku, Kaneto Uekama, Fumitoshi Hirayama

Index: Int. J. Pharm. 453(2) , 315-21, (2013)

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Abstract

A new polymorph of acetohexamide (Form VI) was prepared via the formation of a complex with 2-hydoxybutyl-β-cyclodextrin (HB-β-CD) in aqueous solution. An alkaline solution of acetohexamide and HB-β-CD was adjusted to pH 4.0 by titration with hydrochloric acid. The resulting opaque solution was filtered through paper and allowed to stand at 4°C for 24h. The resulting precipitate was isolated on a filter and analyzed for polymorph content by powder X-ray diffractometry and thermal analysis. The diffraction pattern and thermal behavior of the precipitate was different from those of previously reported acetohexamide polymorphs (Forms I, III, IV and V), indicating that a new polymorph of the drug, i.e. Form VI was produced. This new polymorph was fairly stable against conversion to a stable form even at accelerated storage conditions. Crystalline Form VI was highly soluble in water and dissolved more rapidly than the other known polymorphs. This property was reflected in the blood concentrations of the drug after oral administration to rats. Copyright © 2013 Elsevier B.V. All rights reserved.