Faculty of Pharmacy, King Abdulaziz University, 80260, Jeddah 21589, Saudi Arabia.
Int J Pharm. 2013 Sep 10;453(2):315-21. doi: 10.1016/j.ijpharm.2013.06.026. Epub 2013 Jun 21.
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.
通过在水溶液中与 2-羟丁基-β-环糊精（HB-β-CD）形成复合物，制备了乙酰己脒的一种新多晶型物（形式 VI）。用盐酸将乙酰己脒和 HB-β-CD 的碱性溶液滴定至 pH 4.0。将得到的不透明溶液通过纸过滤，并在 4°C 下放置 24 小时。将得到的沉淀物在过滤器上分离，并通过粉末 X 射线衍射法和热分析法分析多晶型物含量。沉淀物的衍射图谱和热行为与先前报道的乙酰己脒多晶型物（形式 I、III、IV 和 V）不同，表明该药物产生了一种新的多晶型物，即形式 VI。即使在加速储存条件下，这种新的多晶型物也相当稳定，不易转化为稳定形式。结晶形式 VI 在水中的溶解度很高，溶解速度比其他已知的多晶型物更快。这一特性反映在口服给予大鼠后药物的血液浓度上。
