Efficacy and safety of 2% supramolecular salicylic acid compared with 5% benzoyl peroxide/0.1% adapalene in the acne treatment: a randomized, split-face, open-label, single-center study

Cutan Ocul Toxicol. 2019 Mar;38(1):48-54. doi: 10.1080/15569527.2018.1518329. Epub 2018 Dec 20.


Background: Topical drugs for mild to moderate acne include adapalene (ADA) and benzoyl peroxide(BPO). Supramolecular salicylic acid (SSA), a modified SA preparation, is considered as a new effective therapeutic scheme.

Objectives: To compare the safety and efficacy of 2% supramolecular SA (2% SSA) with 0.01% adapalene plus 5% benzoyl peroxide (5%BPO +0.1%ADA) for treatment of facial acne.

Materials and methods: This was an open-label, split face, randomized and single-centre clinical trial. Subjects with mild to moderate acne were enrolled. Two percent SSA cream were randomly applied on one side of the face while 5%BPO +0.1%ADA gel was applied on the opposite side for 28 days. The numbers of acne lesions, along with side effects of the targeted area were evaluated by the investigators at day 0, day 14, and day 28. Skin water content, TEWL and skin lightening indexes were measured at the same time.

Results: A total of 31 of acne patients completed the trial. Dates showed that 2% SSA had similar effects to 5%BPO +0.1%ADA in reducing papules/pustules (47.9% vs. 49.8%), non-inflammatory lesions (43.1% vs. 42.7%) and total lesions (44.1% vs. 45.6%; all p > 0.05) at day 28. The skin barrier (skin hydration value and TEWL value), skin brightness (L* value) and erythema (a* values) indicators showed no statistical differences in the left and right sides of the face (p > 0.05).

Conclusion: This study demonstrated that 2% SSA has a similar efficacy with 5%BPO +0.1%ADA in mild to moderate acne treatment. This might be a useful pilot study that could be used to support further larger clinical trials.

Keywords: Acne; adapalene; benzoyl peroxide; supramolecular salicylic acid; treatment.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Acne Vulgaris / drug therapy*
  • Adapalene / therapeutic use*
  • Administration, Cutaneous
  • Adolescent
  • Adult
  • Benzoyl Peroxide / therapeutic use*
  • Dermatologic Agents / therapeutic use*
  • Drug Combinations
  • Female
  • Humans
  • Male
  • Salicylic Acid / therapeutic use*
  • Treatment Outcome
  • Young Adult


  • Dermatologic Agents
  • Drug Combinations
  • Adapalene
  • Salicylic Acid
  • Benzoyl Peroxide