There are several factors to consider in the formulation process to optimally and safely deliver hydroxy acids to skin. The AHAs, PHAs, and bionic acids are mild, organic acids that are optimally absorbed into skin when present in the free acid, non-ionized form (46). As a result, formulation pH is extremely important. At a defined pH, the concentration of the acid and its pKa determine the amount of free acid and, thus, bioavailability, provided by a formulation (Table 1). As the pH of a formulation is reduced below the pKa of the acid, there is a significant increase in the amount of free acid that is available for penetration. As a result, the potential to cause sensory irritation and erythema increases and must be considered in the formulation process. Formulation technologies exist to facilitate the gradual penetration of free acid into skin, thereby diminishing irritation potential and stinging without reducing skin benefits (46). One such technology utilizes amphoteric amino acids during formulation pH adjustment to temporarily complex free AHA molecules and allow a more gentle delivery of the AHA with reduced irritation and stinging.
Another important factor in the hydroxy acid formulation process involves selection of the specific AHA ingredient. The relatively broad selection of ingredient options provides the formulator with the ability to customize AHA solubility parameters and modify potential skin benefits. For example, the more common AHAs, including glycolic acid and lactic acid, are readily soluble in water. In comparison, those with lipophilic side chains have increased oil solubility and the resultant increased potential to absorb into oily skin and pores. Examples include mandelic acid (phenyl glycolic acid) and benzilic acid (diphenyl glycolic acid) (Fig. 1).