Taylor Dispersion Analysis

This work was carried out in collaboration with the University of Montpellier (France) and led to four publications. TDA enables to determine the size of the micelles and has been used to characterize our self-emulsifyinig excipients Gelucire® 44/14 (Chamieh et al. 2015) and Labrasol® ALF (Chamieh et al. 2016). It has also been used to follow the evolution of micelles during lipolysis (Chamieh et al. 2018) and the release of peptides from SEDDS (Chamieh et al. 2019).


In this technique a microcapillary is used (75 µm section, 75 to 130 cm length) into which a laminar flow of buffer is applied. The sample (solute) is injected in this flow and spreads out axially due to the combined action of convection (red arrow) and radial (blue arrows) diffusion.

Detection of the equilibrium concentration profile (Taylorgram) allows to calculate the absolute molecular diffusion coefficient and hence the hydrodynamic radius of the solute molecules.






Application to Gelucire® 44/14 (Chamieh et al. 2015)

Taylorgrams were obtained for a range of Gelucire® 44/14 concentrations (1 to 70 g/L) and the molecular diffusion coefficient (D) and the hydrodynamic radius (Rh) were calculated.

The results are not impacted by temperature as the radius obtained at 25 and 37°C are identical using TDA, which is not the case with DLS. The difference in the radius obtained by both techniques is explained by the presence of small quantities of large aggregates which give higher radius values using DLS, but not with TDA.

 Gelucire® 44/14 microdroplet radius increases from 1 to 5.5 nm with increasing concentration from 1 to 70 g/L using TDA.

Application to Labrasol® ALF (Chamieh et al. 2016)

Since Labrasol® ALF forms coacervates below 20 g/L at 25°C and below 40 g/L at 37°C, TDA is coupled with fluorescent detection to avoid the noise associated with the coacervates.

Labrasol® AFL microdroplet radius decreases from 90 to 6 nm with increasing concentration from 1 to 70 g/L.


Application to the evolution of micelle size during lipolysis (Chamieh et al. 2018)

The lipolysis test was applied to solutions of Gelucire® 44/14 and Labrasol® ALF. Samples were taken over time and analysed using TDA coupled with fluorescence detection.

During Gelucire® 44/14 lipolysis there is a plateau for about 30-40 min, then the hydrodynamic radius of Gelucire® 44/14 micelles increases with a sigmoidal shape from about 5 nm to about 25 nm.

During Labrasol® ALF lipolysis, the size of the micelles decreases from about 12 nm to reach a plateau at about 3.5 nm after 20 minutes.

Although both excipients behave very differently upon lipolysis, micelles could still be detected up to 120 minutes of digestion.

Application to determine the proportion of peptide in the micelle (Chamieh et al. 2019)

The aim of this study is to quantify the free fraction of peptides in ion pair SEDDS formulations using TDA and leuprorelin and desmopressin as model peptides. The influence of the ionic strength on peptide release is also evaluated.

In the case of leuprorelin the radius decreases exponentially from about 11.9 nm to 2.8 nm at 150 mM ionic strength, suggesting the release of a large amount of peptide.

In the case of desmopressin, the radius decreases from about 4.1 nm to 0.7 nm at 150 mM ionic strength, showing a total release of the peptide.

The proportion of free peptide as a function of ionic strength could be deduced.

Desmopressin appears to be totally released from the SEDDS at physiological saline conditions (150 mM), whereas leuprorelin is released at 80%.