Standardized method for solubility and storage of capsaicin-based solutions for cough induction

Preparation of inhaled capsaicin solutions for cough induction varies greatly from one lab to another, which creates inconsistencies between tussigenic challenge results. The addition of Tween to these capsaicin solutions provides increased solubility and stability; however, the foul taste of Tween makes inhaling the solution for any prolonged period of time unpleasant. We sought to create a standard method for preparing soluble and stable capsaicin-based solutions (in 10% ethanol/water), without the addition of Tween.

Capsaicin solutions were created at concentrations ranging from 0 to 500 μM in a variety of solvent systems, with and without Tween. Samples were stored in four different environments (-20°C, 3°C, and room temperature, protected from light; and room temperature, exposed to light) to test stability. Detection of capsaicin was carried out by UV absorption. A Grubb's test was performed on all data to remove statistical outliers.

Similar capsaicin concentrations were seen for solutions prepared with or without Tween (Tween provided a slight increase in solubility), with neither solvent system providing complete solubility. Of the four environments tested, storing capsaicin solutions at 3°C while protected from light afforded the greatest stability, for a minimum of 30 weeks.

We recommend the use of a 10% ethanol/water solvent system without Tween in the preparation of capsaicin solutions for tussigenic challenges. While this solvent system does not provide complete solubility, we have detailed a method for capsaicin solution preparation that will account for this loss of solubility, while maintaining a solution that is Tween-free and safe for human inhalation.