There are two primary challenges in working with retinoids. One is their tendency to induce skin irritation (as noted above) which negatively affects skin barrier properties. While high doses will provide ever greater skin aging improvement, the associated irritation tends to define an upper concentration limit where they can be used practically. While the skin may have some capacity to accommodate to retinoid treatment to yield less irritation, it is not completely eliminated even with long-term use, as demonstrated by evaluation of skin barrier function (Fig. 4). Mitigation of the irritation may be managed to some extent with appropriate formulation to meter delivery into the skin, use of retinyl esters which are less irritating than retinol (as noted above), or inclusion of other ingredients (e. g., those with anti-inflammatory activity) to counter this issue.
The second key issue is instability, especially to oxygen and light. Thus, to ensure stability of retinoid in the finished product, formulation and packaging must be done in an environment that minimizes exposure to oxygen and light. The final product packaging also ideally needs to be opaque and oxygen impermeable, including use of a small package orifice to reduce oxygen exposure once the container is opened. In addition, a variety of other strategies can be employed, e. g., encapsulation of the retinoid and inclusion of stabilizing antioxidants.