Binary and Ternary Inclusion Complexes of Niflumic Acid: Synthesis, Characterization, and Dissolution Profile
Zohra Bouchekhou,
Amel Hadj Ziane-Zafour,
Florentina Geanina Lupascu,
Bianca-Ștefania Profire,
Alina Nicolescu,
Denisse-Iulia Bostiog,
Florica Doroftei,
Ioan-Andrei Dascalu,
Cristian-Dragoș Varganici,
Mariana Pinteala,
Lenuta Profire,
Tudor Pinteala,
Bachir Bouzid
Affiliations
Zohra Bouchekhou
Chemical Engineering Laboratory, Process Engineering Department, Faculty of Technology, University of Blida 1, Road of Soumaa, BP 270, Blida 09000, Algeria
Amel Hadj Ziane-Zafour
Chemical Engineering Laboratory, Process Engineering Department, Faculty of Technology, University of Blida 1, Road of Soumaa, BP 270, Blida 09000, Algeria
Florentina Geanina Lupascu
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, “Grigore T. Popa” University of Medicine and Pharmacy of Iași, 16 Universitaty Street, 700115 Iași, Romania
Bianca-Ștefania Profire
Department of Internal Medicine, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy of Iasi, 16 University Street, 700115 Iași, Romania
Alina Nicolescu
“Petru Poni” Institute of Macromolecular Chemistry, 41A Grigore Ghica-Voda Alley, 700487 Iasi, Romania
Denisse-Iulia Bostiog
“Petru Poni” Institute of Macromolecular Chemistry, 41A Grigore Ghica-Voda Alley, 700487 Iasi, Romania
Florica Doroftei
“Petru Poni” Institute of Macromolecular Chemistry, 41A Grigore Ghica-Voda Alley, 700487 Iasi, Romania
Ioan-Andrei Dascalu
“Petru Poni” Institute of Macromolecular Chemistry, 41A Grigore Ghica-Voda Alley, 700487 Iasi, Romania
Cristian-Dragoș Varganici
“Petru Poni” Institute of Macromolecular Chemistry, 41A Grigore Ghica-Voda Alley, 700487 Iasi, Romania
Mariana Pinteala
“Petru Poni” Institute of Macromolecular Chemistry, 41A Grigore Ghica-Voda Alley, 700487 Iasi, Romania
Lenuta Profire
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, “Grigore T. Popa” University of Medicine and Pharmacy of Iași, 16 Universitaty Street, 700115 Iași, Romania
Tudor Pinteala
Department of Orthopedics and Traumatology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy of Iasi, 16 University Street, 700115 Iași, Romania
Bachir Bouzid
Chemical Engineering Laboratory, Process Engineering Department, Faculty of Technology, University of Blida 1, Road of Soumaa, BP 270, Blida 09000, Algeria
Although niflumic acid (NA) is one of the most used non-steroidal anti-inflammatory drugs, it suffers from poor solubility, low bioavailability, and significant adverse effects. To address these limitations, the complexation of NA with cyclodextrins (CDs) is a promising strategy. However, complexing CDs with low molecular weight drugs like NA can lead to low CE. This study explores the development of inclusion complexes of NA with 2-hydroxypropyl-β-cyclodextrin (2HP-β-CD), including the effect of converting NA to its sodium salt (NAs) and adding hydroxypropyl methylcellulose (HPMC) on complex formation. Inclusion complexes were prepared using co-evaporation solvent and freeze-drying methods, and their CE and Ks were determined through a phase solubility study. The complexes were characterized using physicochemical analyses, including FT-IR, DSC, SEM, XRD, DLS, UV-Vis, 1H-NMR, and 1H-ROESY. The dissolution profiles of the complexes were also evaluated. The analyses confirmed complex formation for all systems, demonstrating drug–cyclodextrin interactions, amorphous drug states, morphological changes, and improved solubility and dissolution profiles. The NAs-2HP-β-CD-HPMC complex exhibited the highest CE and Ks values, a 1:1 host-guest molar ratio, and the best dissolution profile. The results indicate that the NAs-2HP-β-CD-HPMC complex has potential for delivering NA, which might enhance its therapeutic effectiveness and minimize side effects.
