Quantitative study of solid-state acid-base reactions between polymorphs of flufenamic acid and magnesium oxide using...

Area of Science:

• Solid-state chemistry
• Materials science
• Pharmaceutical sciences

Background:

• Polymorphism significantly impacts drug properties and reactivity.
• Understanding solid-state reactions is crucial for drug formulation and stability.
• Flufenamic acid (FFA) and magnesium oxide (MgO) are common pharmaceutical ingredients.

Purpose of the Study:

• To investigate solid-state acid-base reactions between FFA polymorphs and MgO.
• To characterize the reaction kinetics and identify factors influencing reactivity.
• To explore methods for mitigating undesirable solid-state reactions.

Main Methods:

• X-ray powder diffraction (XRPD) was used to monitor reactions.
• FFA polymorphs were blended with MgO and stored under controlled humidity and temperature.
• Reaction progress was quantified by observing the disappearance of reactants and formation of products.

Main Results:

• Reactions followed the Jander equation, indicating diffusion-controlled processes.
• FFA Form I exhibited higher reactivity with MgO compared to Form III.
• Differential accessibility of reactive groups is a proposed reason for varied reactivity.
• Addition of polyacrylic acid effectively mitigated the acid-base reaction.
• Mixing order of polyacrylic acid and MgO influenced mitigation effectiveness, with co-mixing providing best protection.

Conclusions:

• XRPD is a suitable technique for studying solid-state acid-base reactions.
• Different polymorphic forms of a compound can display distinct solid-state reactivities.
• Solid-state acid-base reactions can be mitigated using "shielding" excipients like polyacrylic acid.