Department of Industrial and Physical Pharmacy, School of Pharmacy and Pharmacal Sciences, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 47907, United States.
J Pharm Biomed Anal. 2010 Mar 11;51(4):866-74. doi: 10.1016/j.jpba.2009.09.021. Epub 2009 Oct 14.
The purpose of this study is to investigate solid-state acid-base reactions between polymorphs of flufenamic acid (FFA) and magnesium oxide (MgO) using X-ray powder diffraction (XRPD). Polymorphs of FFA were blended with MgO and stored under conditions of 96.5% RH and 89% RH at 40 degrees C. The disappearance of FFA and production of magnesium flufenamate were monitored by XRPD. It was observed that the reactions between FFA and MgO proceeded following the Jander equation. Form I of FFA is more reactive with MgO than Form III. Differential accessibility of reactive groups is hypothesized as one of the reasons that Form I is more reactive than Form III. It was noted that the reaction between FFA and MgO could be mitigated by adding another acidic excipient such as polyacrylic acid to prevent the acid-base reaction with FFA. The effectiveness of polyacrylic acid was impacted by the mixing order of the tertiary mixture. Mixing polyacrylic acid and MgO first provided the most significant protection. In conclusion, solid-state acid-base reactions could be investigated using XRPD. Different forms may have distinct reactivity. Acid-base reactions in the solid state could be mitigated through the addition of another "shielding" excipient.
本研究旨在使用 X 射线粉末衍射（XRPD）研究 flufenamic 酸（FFA）多晶型物与氧化镁（MgO）之间的固-酸-碱反应。FFA 的多晶型物与 MgO 混合，并在 40°C、96.5%RH 和 89%RH 条件下储存。通过 XRPD 监测 FFA 的消失和镁 flufenamate 的生成。结果表明，FFA 与 MgO 之间的反应遵循 Jander 方程进行。FFA 的晶型 I 比晶型 III 与 MgO 的反应性更强。假设反应性基团的差异可及性是晶型 I 比晶型 III 反应性更强的原因之一。研究发现，通过添加另一种酸性赋形剂（如聚丙烯酸）来防止与 FFA 的酸碱反应，可以缓解 FFA 与 MgO 之间的反应。聚丙烯酸的效果受到三元混合物混合顺序的影响。首先混合聚丙烯酸和 MgO 可提供最显著的保护。总之，可使用 XRPD 研究固-酸-碱反应。不同的形式可能具有不同的反应性。通过添加另一种“屏蔽”赋形剂可缓解固态中的酸碱反应。
