Nimesulide Apparent Solubility Enhancement with Natural Cyclodextrins and their Polymers

Abstract

The object of this work is to investigate physicochemical characteristics and inclusion behavior of binary systems based on cyclodextrin polymer (Poly-CD) or native cyclodextrins (CDs) with a poorly water-soluble, nonsteroidal anti-inflammatory drug, nimesulide (NIM) chemically, N-(4-nitro-2-phenoxyphenyl)methanesulfonamide. Our formulations were studied in solution and solid-state. Drug-cyclodextrin solid binary systems were prepared by the freezedrying method. Phase solubility study was used to evaluate the interaction in solution, between NIM/CDs and NIM/(Poly-CD). The stability constants of NIM/CDs and NIM/(Poly-CD) complexes were calculated using the phase solubility method. The apparent solubility of NIM was enhanced especially with Poly--CD (up to78-fold) in neutral aqueous solutions without any organic solvents or surfactants. Copmlexes formation was confirmed, in the solid state, by differential scanning calorimetry, infrared spectroscopy and DRX. Complexation spontaneity of drug with cyclodextrin polymers was highlighted using G° values.

Enhanced Dissolution and Oral Bioavailability of Cyclosporine A: Microspheres Based on αβ-Cyclodextrins Polymers

“…Complexing agents such as cyclodextrins or calixaren are particularly very interesting tools for maintaining poor water soluble drugs molecularly into such drug delivery systems by complexing them into the cavities of poly-cyclodextrins [9]. It has been shown that manufacturing solid dispersions can improve the solubility of drugs such as nimesulide, albendazole, and piroxicam [10,11,12].…”

Interaction Study of an Amorphous Solid Dispersion of Cyclosporin A in Poly-Alpha-Cyclodextrin with Model Membranes by 1H-, 2H-, 31P-NMR and Electron Spin Resonance

“…For this specific kind of drug, many enabling technologies are available for the formulator to consider, including lipids, cosolvents, surfactants, nanoparticles, cyclodextrin complexes, and amorphous solid dispersions. The suitability of a particular formulation approach depends largely on the physicochemical properties of the active pharmaceutical ingredient (API) [ 3 ]. Among these methods, the preparation of amorphous solid dispersions (ASD) with cyclodextrin copolymer (POLYA) is particularly attractive for many poorly water-soluble drug candidates [ 4 ] because these formulations offer many of the advantages of more conventional solid oral dosage forms and also provide faster dissolution rates and higher drug concentrations in the gastrointestinal milieu [ 3 ].…”

Nimesulide Based Novel Glycolamide Esters: Their Design, Synthesis, and Pharmacological Evaluation

“…We anticipated that combining the structural features of nimesulide and glycolamide esters in a single molecule may afford novel template for the design and synthesis of new anticancer agents. Notably, the cyclooxygenase-2 (COX-2) inhibitor nimesulide is known to possess anticancer properties [21,22] whereas the glycolamide esters are known to impart favorable pharmacological properties. Herein we report the synthesis and in vitro cytotoxic effects of a series of novel glycolamide esters A derived from nimesulide.…”