Amphiphilic association of ibuprofen and two nonionic cellulose derivatives in aqueous solution

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Abstract

The aqueous interaction of the sodium salt of ibuprofen with the cellulose ethers ethyl hydroxyethyl cellulose, EHEC, and hydroxypropyl methyl cellulose, HPMC, has been investigated in the concentration range 0-500 mM ibuprofen and 0.1-1% (w/w) polymer, by cloud point, capillary viscometry, equilibrium dialysis, and fluorescence probe techniques. Ibuprofen forms micelles in pure water, with the critical micelle concentration, cmc, at 180 mM. A combination of time-resolved and static fluorescence quenching shows that micelle-like ibuprofen aggregates are formed in the solution. The average aggregation number of pure ibuprofen micelles in water is about 40. In the presence of EHEC or HPMC the aggregation numbers decrease. The interaction of ibuprofen with cellulose ethers is similar to the normally accepted model for polymer-surfactant interaction, although more complex. Ibuprofen adsorbs to the polymer in the form of mixed polymer-drug micelles, noncooperatively up to cmc and cooperatively when cmc is passed. The interaction starts below 50 mM ibuprofen as monitored by the fluorescent probes pyrene and 1,3-di(1-pyrenyl)propane, P3P, with a maximum in microviscosity below cmc, corresponding to polymer-dense mixed micelles. The study illustrates the importance of a precise apprehension of the aggregation behavior as a background for transport studies in drug-polymer systems.

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