To the Editor: Phenol–croton oil formulas contained Septisol (SEP) (Steris, Mentor, OH), a discontinued antiseptic handwash that contained sodium C14-16 olefin sulfonate as the surfactant.
Currently, PEG-80 sorbitan laurate, Novisol, (NOV) (Young Pharmaceuticals, Wethersfield, CT) has been adopted by some specialists because of improved chemical stablility.
Before NOV, we explored the use of Johnson’s baby shampoo (JBS) (Johnson & Johnson do Brasil, São Paulo, Brazil), which contains a long list of surfactants. We aimed to characterize the role of formula stability in 1.2% croton oil in 35% phenol peels
mixed with SEP or JBS.
Chemical studies were performed by macroscopy, microscopy, and zeta potentials analysis (see Supplement 1, available via Mendeley at https://doi.org/10.17632/n5n5mfkkhb.1). A clinical study was performed by a split-face, double-blind, randomized trial that enrolled 12 women (skin types I-III) for the treatment of photoaging (Glogau types III-IV) (see Supplement 2 available via Mendeley at https://doi.org/10.17632/kbhjfzsgk2.1). Three blinded graders scored baseline and 6-month postprocedure photographs. Efficacy was evaluated by using a validated photonumeric scale, and safety was evaluated by irregularity of results, defined as 1 side showing increased contrast between areas of persistent photoaging and areas of smooth texture (see Supplement 3 available via Mendeley at https://doi.org/10.17632/2fj4y7gpv9.1).
Both the SEP and JBS formulas were unstable biphasic dispersions. Charge distribution was not maintained during the first minute after homogenization, indicating high droplet movement and coalescence. Dispersion instability was observed macroscopically and microscopically with almost immediate phase separation. Unstable dispersions exhibited rapid coalescence of active droplets (phenolic phase) (Supplemental Video 1 available on jaad.org). This accelerated coalescence results in a concentrated lower layer within the first minute (Fig 1). Clinically, although similar improvement was observed (P < .000001) for both SEP and JBS, JBS presented the most irregular results, in 68% of the blinded evaluations versus 32% for SEP (P = .050). One patient developed bilateral leucodermic superficial scars.
Fig 1Instability of chemical peel formulas containing Septisol (SEP) or Johnson’s Baby Shampoo (JBS) (Johnson & Johnson do Brasil, São Paulo, Brazil). Zeta potential distribution analysis immediately after homogenization and 1 minute after homogenization. Macroscopy: at 1 minute after homogenization, the upper layer was evident in both formulas; however, JBS had increased instability and separation, with a more concentrated active lower phase in 1 minute.
Lack of stability produces a higher-than-intended concentration of active ingredients in the lower part of the cotton-tipped applicator within seconds (JBS > SEP), which translates into increased action in some areas throughout the procedure and irregular results (making JBS less safe than SEP) (Fig 2). Emulsion stability improved the efficacy and safety of phenol–croton oil formulas in vivo.
One example was presented in a recent illustrative case that showed irregular distribution of prolonged healing zones with SEP, whereas with NOV, the healing was uniform.
In spite of areas of prolonged healing, possibly due to the increased depth with SEP,
the final results with the more stable NOV emulsion are clinically comparable.
Thus, with a stable formula, the depth of injury is determined primarily by the concentration of croton oil and the aggressiveness of application. With unstable formulas, other determinants such as time between agitation and application also influence effects. Limitations include the fact that the composition of JBS varies slightly by country.
Fig 2Phenol–croton oil peel. Illustrative front view of a female patient treated with chemical peel formulas containing Septisol (SEP) or Johnson’s Baby Shampoo (JBS) (Johnson & Johnson do Brasil, São Paulo, Brazil) after 6 months. Griffiths photonumeric scale grading (median): SEP before, 7; SEP after, 4; JBS before, 8; JBS after, 5. Safety evaluation: the JBS side was graded as most irregular by 2 blinded evaluators. One blinded evaluator considered both sides symmetric. If the percentage of croton oil was increased (not allowed during the trial), more improvement of severe photoaging areas of the skin would be noticed.
These results suggest that comparable efficacy is achieved with the same concentrations of active ingredients. However, formula stability affected the uniformity of results, with the JBS formula leading to more irregular results due to faster separation despite meticulous agitation.
Emulsifying agents influence safety through their effect on formula stability, which is required for uniform and reproducible results. We do not recommend adopting JBS, or unstable formulas, based on these findings.
The authors are grateful for the technical support from the Multiuser Laboratory of Biology and Health Science Center of the State University of Ponta Grossa.
References
da Silva Justo A.
Lemes B.M.
Nunes B.
et al.
Depth of injury of Hetter’s phenol-croton oil chemical peel formula using 2 different emulsifying agents.
Disclosure: Dr Wambier serves as an advisor for Young Pharmaceuticals, Inc, and has a patent application on the emulsification of phenol–croton oil formulas. Drs Neitzke and de Grande Curi, Author Lin, and Drs Lee, Soon, Bittencourt, Aguiar, Neto, Filha, Beltrame, and Döll-Boscardin have no conflicts of interest to declare.
IRB approval status: Reviewed and approved by the ethics committee of Hospital Heliopolis (no. 2.796.366).
