Binary and Ternary Inclusion Complexes of Niflumic Acid: Synthesis, Characterization, and Dissolution Profile.

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Materials Science

Background:

• Niflumic acid (NA), a widely used NSAID, exhibits poor solubility, low bioavailability, and adverse effects.
• Cyclodextrin (CD) complexation is a strategy to improve drug properties, but low molecular weight drugs like NA can result in low complexation efficiency (CE).

Purpose of the Study:

• To develop inclusion complexes of NA with 2-hydroxypropyl-β-cyclodextrin (2HP-β-CD).
• To investigate the effects of converting NA to its sodium salt (NAs) and incorporating hydroxypropyl methylcellulose (HPMC) on complex formation, CE, and drug release.
• To characterize the physicochemical properties and dissolution profiles of the developed complexes.

Main Methods:

• Inclusion complexes were prepared using co-evaporation solvent and freeze-drying techniques.
• Phase solubility studies were employed to determine complexation efficiency (CE) and binding constants (Ks).
• Physicochemical characterization involved FT-IR, DSC, SEM, XRD, DLS, UV-Vis, 1H-NMR, and 1H-ROESY analyses.

Main Results:

• Complex formation was confirmed for all systems, indicating drug-cyclodextrin interactions, amorphous drug states, and morphological changes.
• The NAs-2HP-β-CD-HPMC complex demonstrated the highest CE and Ks values, with a 1:1 host-guest molar ratio.
• Improved solubility and dissolution profiles were observed for the developed inclusion complexes, particularly the NAs-2HP-β-CD-HPMC formulation.

Conclusions:

• The developed inclusion complexes, especially NAs-2HP-β-CD-HPMC, show significant improvements in NA solubility and dissolution.
• This formulation holds potential for enhanced therapeutic efficacy of NA while minimizing adverse effects.
• The study highlights the successful application of 2HP-β-CD and HPMC in developing advanced drug delivery systems for poorly soluble NSAIDs.