Solubilization of flurbiprofen within non-ionic Tween 20 surfactant micelles: a 19F and 1H NMR study

Abstract

The solubilization of the poorly water soluble anti-inflammatory drug flurbiprofen in non-ionic Tween 20 surfactant micellar solutions was studied by both (19)F and (1)H NMR spectroscopy in an acidic environment. These non-destructive techniques allowed us to investigate the effect of temperature cycling in situ. Using (19)F NMR, an increased solubilisation capacity was observed as the temperature increased. This effect became more pronounced above the cloud point, which was reduced by more than 30 degrees C in the presence of an excess of flurbiprofen. Upon clouding, peak splitting was observed in the (19)F spectrum, which indicates that two pools of solubilised flurbiprofen exist that are in slow exchange on the NMR frequency timescale. The clouding and solubilization processes were found to be reversible, albeit with slow kinetics. Based on chemical shift differences of both Tween 20 and flurbiprofen, as well as NOESY experiments, the flurbiprofen was found to be accumulated within the palisade layer of the Tween 20 micelles.

Peculiar Mechanism of Solubilization of a Sparingly Water Soluble Drug into Polymeric Micelles. Kinetic and Equilibrium Studies

“…As copolymers, we have used the series PHEA-PEG 2000 -C 16 , PHEA-PEG 5000 -C 16 , and PHEA-C 16 having different hydrophilic/hydrophobic ratios. Since each solubilization process reaches the equilibrium state, the final absorbance value has been recorded for all copolymer concentrations.…”

“…O-(2-aminoethyl)-O′-methylpoly(ethylene glycol) 2000 (PEG 2000 −NH 2 ) (<0.4 mmol NH 2 /g) and O-(2-aminoethyl)-O′-methyl(polyethylene glycol) 5000 (PEG 5000 −NH 2 ) (<0.17 mmol NH 2 /g) and all the other chemicals were purchased from Fluka. α,β-Poly(N-2-hydroxyethyl)-DL-aspartamide (PHEA) and the PHEA derivatives (PHEA-PEG 2000 , PHEA-PEG 5000 , PHEA-PEG 2000 -C 16 , PHEA-PEG 5000 -C 16 , and PHEA-C 16 ) were prepared and purified according to a previously reported procedure. 7−9 Stock solutions of all copolymers were prepared by weight.…”

“…In a previous paper, poly(hydroxyethylaspartamide) (PHEA) derivatives bearing poly(ethylene glycol) (2000 or 5000 Da) or both poly(ethylene glycol) and hexadecylalkylamine (C 16 ) as pendant moieties were investigated as polymeric colloidal drug carriers. The ability of the PHEA derivatives to solubilize hydrophobic drugs was investigated using paclitaxel, amphotericin B, and methotrexate 9 or dexamethasone.…”

“…As copolymers we have used the series PHEA-PEG 2000 -C 16 , PHEA-PEG 5000 -C 16 , and PHEA-C 16 having different hydrophilic/hydrophobic ratios, whose physicochemical characterization has been previously performed. 20 Briefly, it has been obtained that these copolymers are able to self-aggregate into micelles and the cac is very low.…”

Solubilization of flurbiprofen with non-ionic Tween20 surfactant micelles: A diffusion 1H NMR study

“…Upon clouding, peak splitting was observed in the 19 F spectrum, which indicated the presence of two different pools of solubilized flurbiprofen in slow exchange on the 19 F frequency timescale. Peak splitting was also observed in the 1 H spectrum: additional small peaks occurred at about 0.1 ppm upfield to the original ones [9]. To investigate the nature of these different environments, we studied the diffusion behaviour of the different species present in both saturated and unsaturated mixtures 4 of flurbiprofen and Tween20 as a function of temperature by 1 H-NMR.…”