TOPICAL FORMULATION TO IMPROVE HYPERPIGMENTATION 277 4% or HQ4% on either side of their face demonstrated that niacinamide was an effec- tive alternative to HQ. Posttreatment biopsies indicated a signifi cant reduction in the amount of epidermal melanin and infl ammatory infi ltrate in the niacinamide treated side. Although no statistically signifi cant difference was found using a colorimetric as- sessment, HQ4% demonstrated a higher frequency of moderate adverse effects relative to niacinamide (18% vs. 7%, respectively). No signifi cant side effects were observed following treatment with niacinamide, allowing it to be used for longer time periods (25). V itamin C and arbutin also provide skin-lightening benefi ts. Vitamin C, also known as ascorbic acid, contains antioxidant properties capable of hindering melanin synthesis by reducing o-dopaquinone to DOPA (21). Vitamin C has been shown to improve photoaging and hyperpigmentation in studies when used in combination with other skin-lightening agents (22,23). Vitamin C is readily oxidized, and in our formulation, we used a form which helped maintain its stability more effectively. Arbutin is a b-D-glucopyranoside derivative of HQ that can be extracted from bearberry, pear, cranberry, or blueberry plants (38). Arbutin is an inhibitor of tyrosinase and can inhibit melanosome maturation (24,39). T here are some limitations to our study that should be mentioned. The duration of study was only 1 mo, which could be perceived as being too short for appropriate evaluation. Despite the 1-mo follow-up, our study showed that there was a signifi cant improvement in the overall appearance of hyperpigmentation using SKNB19 when compared with Figure 14. Three-dimensional photographic comparison of left-sided facial hyperpigmentation (cheek area) before (left) and after (right) 4 wk of twice-daily application HQ4% in a 35-year-old woman.

JOURNAL OF COSMETIC SCIENCE 278 HQ4%. Nevertheless, future studies should use a larger patient population and follow the cohort for a longer period of time to uncover whether longer use of this product may result in potentially even better outcomes. A nother limitation is the difference of application frequency between the two products investigated. It would have been ideal if both HQ4% and SKNB19 were applied twice daily. In our clinical practice, HQ4% is recommended to be used once a day because of its tolerance issues. Although it would have been ideal to dose the two products twice daily, we wished to stay consistent with our clinical practice patterns. In considering our pro- tocol for our study, increasing HQ4%’s dose to twice daily may have increased the degree of improvement in the treated areas of hyperpigmentation, but this increase in frequency would potentially increase the chances of HQ4%-related adverse effects. We wanted to establish a study methodology that was most consistent with our clinical practice pat- terns. Nevertheless, this creates a potential limitation to HQ4%’s full potential and cre- ates a bias in our study, which we are aware of, but given that SKNB19 could be tolerated twice daily, we wished to investigate SKNB19 at this ideal frequency interval. A nother area of limitation in our study is the differences in formula bases, or excipient bases, that were used between the two products. Although we were effectively evaluating the active ingredients between SKNB19 and HQ4%, each had differing excipient bases, which can arguably affect stability and absorption effi cacy of the active ingredients and Figure 15. Three-dimensional photographic comparison of right-sided facial hyperpigmentation (cheek area) before (left) and after (right) 4 wk of twice-daily application SKNB19 in a 35-year-old woman. The subject reported moderate irritation and redness at the 4-wk visit with the HQ4%-treated side (Figure 14). SKNB19-treated hyperpigmentation shows a noticeable improvement in hyperpigmentation compared with the side treated with HQ4% (Figure 14).