Guo Y, Byrn S R, Zografi G
School of Pharmacy, University of Wisconsin-Madison, 53706, USA.
Pharm Res. 2000 Aug;17(8):930-5. doi: 10.1023/a:1007519003070.
To prepare amorphous quinapril hydrochloride (QHCl) by lyophilization and to compare its physical characteristics and chemical stability as a function of the initial pH of the pre-lyophilized solution.
Amorphous QHCl samples were prepared by lyophilization from aqueous solutions. Solid-state characteristics were evaluated by DSC, PXRD, and optical microscopy. Chemical degradation was monitored by an HPLC assay.
Amorphous QHCl samples obtained from lyophilization exhibited variable glass transition temperatures, depending on the pH and/or concentration of the starting aqueous solutions. Neutralized quinapril (Q) in the amorphous form, which has a Tg of 51 degrees C, lower than that of its HCl salt (91 degrees C), was significantly more reactive than QHCl at the same temperature. The Tg of lyophilized samples prepared at various initial pH values correlated well with values predicted for mixtures of QHCl and Q. Their different reaction rates were related to their glass transition temperature, consistent with the results from earlier studies obtained with amorphous samples made by precipitation from an organic solution and grinding of the crystal solvate.
Lyophilization of different QHCl solutions produces mixtures of amorphous QHCl and its neutralized form Q, with Tg values intermediate to the values of QHCl and Q. As the fraction of Q increases the overall rate of chemical degradation increases relative to QHCl alone, primarily due to the increase in molecular mobility induced by the plasticizing effects of Q.
通过冻干法制备无定形盐酸喹那普利（QHCl），并比较其物理特性和化学稳定性与冻干前溶液初始pH值的关系。
从水溶液中通过冻干法制备无定形QHCl样品。通过差示扫描量热法（DSC）、粉末X射线衍射（PXRD）和光学显微镜评估固态特性。通过高效液相色谱法（HPLC）测定监测化学降解。
冻干得到的无定形QHCl样品表现出可变的玻璃化转变温度，这取决于起始水溶液的pH值和/或浓度。无定形形式的中和喹那普利（Q）的玻璃化转变温度为51℃，低于其盐酸盐（91℃），在相同温度下，其反应活性明显高于QHCl。在各种初始pH值下制备的冻干样品的玻璃化转变温度与QHCl和Q混合物预测的值相关性良好。它们不同的反应速率与其玻璃化转变温度有关，这与早期通过从有机溶液中沉淀和研磨晶体溶剂化物制备的无定形样品的研究结果一致。
不同QHCl溶液的冻干产生无定形QHCl及其中和形式Q的混合物，其玻璃化转变温度值介于QHCl和Q的值之间。随着Q比例的增加，相对于单独的QHCl，化学降解的总体速率增加，这主要是由于Q的增塑作用引起的分子流动性增加。
