CMC determination using isothermal titration calorimetry for five industrially significant non-ionic surfactants.

Surfactants are used in a vast array of products including pharmaceuticals, cosmetics and household formulations. From an industrial perspective, non-ionic surfactants are ideal for inclusion within such products as they are non-toxic, simple to formulate and economic to use. This study considers five non-ionic surfactants (Tween 20, Tween 80, Crodasol, Croduret and Etocas 35) to determine the critical micellar concentration (CMC) for each using isothermal titration calorimetry, thus avoiding issues regarding poor accuracy found with other techniques. Furthermore, this methodology has not previously been applied to this group of surfactants. For the most commonly used non-ionics (Tween 20 and Tween 80) a further study was undertaken to consider the influence of surfactant purity on the CMC determined, using standard grade (Tween 20 and 80), high purity (Tween 20 HP and Tween 80 HP) and Super Refined (SR PS20 and SR PS80). Results permitted calculation of the CMC for the surfactants whereupon the values were determined to range from 1.0 mM for Tween 20 HP to 2.9 mM for Tween 80 HP. Such information regarding the CMC event is useful from a formulation perspective as it can ensure that the most optimum concentration of surfactant is included within a formulation to maximize its efficacy.

Understanding polysorbate-compound interactions within the CMC region.

Non-ionic surfactants such as polysorbates, known as Tween™ 20 and Tween™ 80, are routinely used within the healthcare and pharmaceutical industry to enhance solubility. This work focuses on analysing the two aforementioned polysorbates, each considered at three purity levels with four model compounds, across the critical micellar concentration (CMC) range for each surfactant. Such data is of interest to investigate the influence of micelle formation upon compound-polysorbate interaction. Two analytical techniques were utilised, namely spectroscopic solubility determination and micellar liquid chromatography (MLC). In all cases it was apparent that the maximum solubility for all four compounds increased substantially at concentrations greater than the CMC and that, in most cases, a different retention profile was observed using MLC once the CMC had been exceeded. This paper is the first to have used such techniques to investigate the behaviour of these polysorbates over a series of concentrations and three levels of polysorbate purity. The findings indicate that the solubilisation potential of polysorbates differs once the CMC has been surpassed and is dependent upon the level of purity selected, i.e. compound-surfactant interactions are partially a consequence of the presence of micelles rather than monomer as well as polysorbate purity. Thus, formulators should include such polysorbates at optimised concentrations and purity if they wish to maximise their solubilisation potential.

N-Alkylation and Aminohydroxylation of 2-Azidobenzenesulfonamide Gives a Pyrrolobenzothiadiazepine Precursor Whereas Attempted N-Alkylation of 2-Azidobenzamide Gives Benzotriazinones and Quinazolinones.

N-Alkylation of 2-azidobenzenesulfonamide with 5-bromopent-1-ene gave an N-pentenyl sulfonamide, which underwent intramolecular aminohydroxylation to give an N-(2-azidoaryl)sulfonyl prolinol, a precursor for the synthesis of a pyrrolobenzothiadiazepine. The attempted N-alkylation of 2-azidobenzamide gave a separable mixture (∼1:1) of a benzotriazinone and a quinazolinone in a 72% combined yield. Other primary alkyl halides (3 examples) gave similar mixtures of benzotriazinones and quinazolinones. Benzylic, allylic, and secondary and tertiary alkyl halides (5 examples) gave only benzotriazinones in moderate yields. The results of mechanistic studies show the likely involvement of nitrene intermediates in the quinazolinone pathway and a second pathway involving a dimethylsulfoxide or dimethylsulfide-mediated conversion of 2-azidobenzamide into benzotriazinones.