Novel Polymorphic Cocrystals of the Non-Steroidal Anti-Inflammatory Drug Niflumic Acid: Expanding the Pharmaceutical Landscape
Metadata
Show full item recordAuthor
Acebedo Martínez, Francisco Javier; Alarcón Payer, Carolina; Di Crisci, Milena; Domínguez Martín, Alicia; Gómez Morales, Jaime; Choquesillo Lazarte, DuaneEditorial
MDPI
Materia
Cocrystal polymorphism Niflumic acid Caffeine NSAIDs Mechanochemical synthesis
Date
2021-12-13Referencia bibliográfica
Acebedo-Martínez, F.J... [et al.]. Novel Polymorphic Cocrystals of the Non-Steroidal Anti-Inflammatory Drug Niflumic Acid: Expanding the Pharmaceutical Landscape. Pharmaceutics 2021, 13, 2140. [https://doi.org/10.3390/pharmaceutics13122140]
Sponsorship
Spanish Agencia Estatal de Investigacion of the Ministerio de Ciencia, Innovacion y Universidades (MICIU); European Commission PGC2018-102047-B-I00; FEDER-Universidad de Granada, Spain B-FQM-478-UGR20; MCIU/AEI of Spain PID2020-115637GB-I00 PRE2019-088832Abstract
Any time the pharmaceutical industry develops a new drug, potential polymorphic events
must be thoroughly described, because in a crystalline pharmaceutical solid, different arrangements
of the same active pharmaceutical ingredient can yield to very different physicochemical properties
that might be crucial for its efficacy, such as dissolution, solubility, or stability. Polymorphism in
cocrystal formulation cannot be neglected, either. In this work, two different cocrystal polymorphs
of the non-steroidal anti-inflammatory drug niflumic acid and caffeine are reported. They have
been synthesized by mechanochemical methods and thoroughly characterized in solid-state by
powder and single crystal X-ray diffraction respectively, as well as other techniques such as thermal
analyses, infrared spectroscopy and computational methods. Both theoretical and experimental
results are in agreement, confirming a conformational polymorphism. The polymorph NIF–CAF
Form I exhibits improved solubility and dissolution rate compared to NIF–CAF Form II, although
Form II is significantly more stable than Form I. The conditions needed to obtain these polymorphs
and their transition have been carefully characterized, revealing an intricate system.