Mechanochemical synthesis, characterization, and thermal behavior of meloxicam cocrystals with salicylic acid, fumaric acid, and malic acid

Author(s)

Fernandes, Richard Perosa ^[1] ; Carneiro Soares do Nascimento, Andre Luiz ^[1] ; Sobral Carvalho, Ana Carina ^[1] ; Teixeira, Jose Augusto ^[1] ; Ionashiro, Massao ^[1] ; Caires, Flavio Junior ^{[1, 2]}

Affiliation

^[1] Univ Estadual Paulista UNESP, Inst Quim, CP 355, BR-14801970 Araraquara, SP - Brazil

^[2] Univ Estadual Paulista Unesp, Fac Ciencias, BR-17033260 Bauru, SP - Brazil

• Document type: Journal article
• Source: JOURNAL OF THERMAL ANALYSIS AND CALORIMETRY; v. 138, n. 1, p. 765-777, OCT 2019.
• Web of Science Citations: 3

Abstract

A liquid-assisted grinding approach was used to synthesize three cocrystals between the coformers: salicylic acid, fumaric acid, and malic acid with meloxicam, a nonsteroidal anti-inflammatory drug. The spectroscopic techniques, Raman and Fourier transform infrared (FTIR), confirm the formation of these compounds by showing evidence of hydrogen bonds between NH or OH and CO groups. Powder X-ray diffraction verified the formation of the cocrystals by comparing the results with a crystallographic database. Differential scanning calorimetry (DSC), simultaneous thermogravimetry and differential scanning calorimetry (TG-DSC), evolved gas analysis (EGA by TG-FTIR), DSC-photovisual analysis, and videos of the cocrystals being heated were used to study the thermal behavior, analyze the composition, identify polymorphic transitions in meloxicam cocrystal with malic acid, and understand the decomposition phenomena of these solids. The malic acid compound shows a unique degradation step that was confirmed by TG-DSC data and FTIR analysis of the residue formed. A solubility test was performed: fumaric cocrystal showed an enhanced performance compared to pure drug, and malic and salicylic cocrystals showed a slower dissolution profile. (AU)

• FAPESP's process: 18/24378-6 - Synthesis, characterization and thermoanalytical study of Valsartan, Candesartan Cilexetil and Olmesartan medoxomil co-crystals
• Grantee: Flávio Junior Caires
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/14936-9 - Preparation, characterization and thermoanalytical studies of heterogeneous catalysts of double selenates of Mg/Co and Mg/Cu in biodiesel production using different oils
• Grantee: Massao Ionashiro
• Support Opportunities: Regular Research Grants