Original Contribution Journal of Cosmetic Dermatology, 12, 41--48

Effect of essential oils, hydrating agents, and ethanol on hair removal efficiency of thioglycolates Hamid R Moghimi, PhD,1,2 Bardia Jamali, PharmD,1 Sara Farahmand, PharmD,1 & Bijan Shafaghi, PhD1 1 2

School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran Pharmaceutical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Summary

Background The required time for hair removal by chemical depilatories has always been a concern and depends on different parameters including permeation into the hair shaft. Objectives In an attempt to improve this process, it was decided here to investigate the possibility of decreasing depilation time of thioglycolates, widely used depilatories, using penetration enhancers. Methods Urea, sodium dodecyl sulfate, dimethylsulfoxide (DMSO), ethanol (75 and 96%), NaCl, and peppermint and orange oils were used as penetration enhancers, and their effect on depilatory time of thioglycolates, represented as tear resistance time (TRT) of hair shaft under a constant tensile stress, was studied. The effects of temperature and hydration on TRT were also investigated. Results Results showed that ethanol (75%), DMSO, and peppermint oil (ethanolic solution) were able to significantly reduce TRT up to two times from about 6 to 3.5 min. Other enhancers were not able to change TRT. Results also revealed that increase in temperature from 20 to 37 °C reduces TRT by about 4 times. Hydration in boiling water also reduced TRT significantly about 1.5 times. Conclusions Present results show that it is possible to reduce depilation time by penetration enhancers. Such improvement can increase users’ compliance and might provide other advantages like decreased skin irritation. Keywords: chemical depilatories, thioglycolates, temperature, penetration enhancers, depilation time

Introduction The importance of hair removal either to change or improve the appearance, or for any other reasons, has led human to try different methods since ancient times.1 Various hair removal methods are available nowadays of which chemical depilatory formulations, Correspondence: H R Moghimi, PhD, Department of Pharmaceutics, School of Pharmacy, Shahid Beheshti University of Medical Sciences, PO Box: 14155-6153, Tehran, Iran. E-mail: [email protected] Preliminary data were presented as a poster in the 11th Iranian Pharmaceutical Sciences Conference (18–21 August 2008), Kerman, Iran. Accepted for publication February 16, 2012

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due to ease of application and suitable duration, have attracted more attention among the methods of removing unwanted hair.1,2 These products act by reducing the cystine linkages (disulfide bonds) of the hair keratin. This is accomplished by the use of inorganic sulfides, stannites, or organic thioglycolates. Thioglycolatecontaining formulations, due to less malodor of sulfur, less skin irritation, and good stability, have the widest application. Thioglycolate salts with pH values of 11– 12.5 and concentration of 2.5–8% are preferred.1,3 Reducing the cystine linkages in hair shaft depends on the hydroxyl concentration, time of reaction, and temperature.1 Thus, increasing the pH enhances depilation, and alkaline pHs are needed for this process.1,4,5

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. H R Moghimi et al.

Skin usually can tolerate pHs 3.5–8.5,6 and high pHs are irritating to skin. The pH in depilatory creams, which are used in short times, should not exceed 12.5.2 To avoid skin damage, chemical depilatories should have minimum contact time with the skin or their pHs reduced. Depilatory activity of thioglycolate depends on their salts as well.7 Lithium, sodium, and potassium salts, because of greater solubility, show accelerated depilatory action but sodium and potassium are more irritating to skin than calcium thioglycolate.1 Barium and calcium have shown lower irritation effect, of which calcium thioglycolate is faster in removing hair.7 Therefore, calcium thioglycolate maybe preferred but its depilation time is slow, and this problem is greater for dark and thick curly hairs.8 To overcome this problem, different methods have been employed for depilatory acceleration. It has been claimed that guanidine increases the permeability of hair shafts, and thus increase the rate of reaction of thioglycolates with hair.2 It has also been reported that thiourea functions as accelerator for thioglycolic acid, and formulations containing this compound are useful in removing facial hair, especially in Negro males.9 Other accelerators include silicates, dicyandiamide, inorganic thiocyanate,1 aminoguanidine, biguanide,2 dimethyl isosorbide, ethoxydiglycol, methyl propyldiol,10 melamine,11 thioredoxin, and derivatives or thioredoxin-like dithiol peptides.12 Most of the above mentioned depilatory accelerators act through either pH increase (e.g., guanidine, aminoguanidine) or are hair removing agents themselves, and therefore act as additives or synergistic (e.g., thioredoxin,12 dimethyl isosorbide10). It has been demonstrated that vehicle modification can improve depilation effect. It has been reported that O/W emulsion needs less time than W/O emulsion for hair removing.1,4,13 Physical enhancement methods like iontophoretic has also been used for improved depilatory effects of thioglycolate8 but such a method is really difficult to be commercialized and can also be considered invasive. Therefore, it was decided here to find safer and more acceptable methods to decrease depilation time, by using the so-called chemical permeation enhancers and hydration of hair shafts. Enhancers are generally used to increase permeation of drugs through biological barriers, including skin. Some penetration enhancers, like essential oils, urea, surfactants, and alcohols, are widely used in many cosmetic products such as fragrance and hydrating creams. Therefore, it was decided here to investigate the effects of such material

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on depilatory efficiency of thioglycolate. This approach is novel, and to the best of our knowledge, there is not such a study reported in the literature.

Materials and methods Materials

DMSO (99.95%), 1,2-propanediol, stearic acid, liquid paraffin, propyl paraben, sodium chloride, sodium hydroxide, cetyl alcohol, methyl paraben, Span 60, urea, Tween 80, and sodium dodecyl sulfate (all pharmaceutical grade) were purchased from Merck (Darmstadt, Germany). Peppermint oil and orange terpenless oil were purchased from Dullberg Konzentra GmbH & Co. (Hamburg, Germany). Based on the provided certificate of analysis, the used peppermint oil contains 47.1% l-menthol, 22.4% menthone, 10.1% cineole, 6.0% menthylacetate and, at lower concentrations, other terpenes like limonene, menthofurane, isomenthone, isopulegol, carvone, and pulegone. The used orange terpenless oil contains 57.3% d-limonene, 20.2% aldehyde, and 18.8% linalool. Absolute ethanol (99.9%) was purchased from Temad (Tehran, Iran), ethanol (96%) was supplied by Taghtir Khurasan Co. (Iran), and Carbomer 940 (USP grade) was obtained from BF Goodrich Company (USA). Calcium thioglycolate was obtained from Goldschmidt GMBH (Germany). Lanolin and beeswax (both USP grade) were received as gifts from Farmashimi (Tehran, Iran). Depilatory formulations

Two depilatory formulations were used in this study. Veet®, a well-known commercial depilatory cream (Reckitt Benckiser, Massy, France) containing potassium thioglycolate as the active ingredient was purchased from local pharmacy. A stable O/W calcium thioglycolate depilatory cream containing liquid paraffin, Span 60, cethyl alcohol, propyl paraben, lanolin, bees wax, propylene glycol, Tween 80, distilled water, and 6% (w/w) calcium thioglycolate with pH 12 was prepared here as the plane (base cream) from which enhancer-containing creams were prepared as follows. Calcium thioglycolate creams containing 30% (w/w) DMSO (equal to 60% DMSO in the aqueous phase of the cream) and creams containing 13% (w/w) ethanol were prepared separately by addition of enhancers to calcium thioglycolate base cream and final pH adjustment to 12. Higher ethanol concentrations than 13% (w/w) caused cream instability and were not used.

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Effect of chemical enhancers on efficacy of depilatories

Hair samples

Scalp hair, that has been shown to be a good model for evaluation of depilatory effect of cosmetic formulations and is morphologically similar to leg hairs,14 was used as a model in the present investigation. These hairs were collected from two young persons (12–14 years old) at the time of their usual hair cut in a hairdresser’s with permission and in the presence of their mothers. According to the subjects, the hair shafts had not been treated before by hair colors, strainers, hair conditioners, bleachers, or other cosmetic formulations, and the only treatments had been normal bath shampoos. To the best of our knowledge, there is no data available on the effects of age on the response to depilatory formulations. However, it is worth to note that depilatory creams are the preferred hair removal method in treatment of hypertrichosis by teenagers as young as 13 years old.15 This study is performed according to protocols of ethics committee of Shahid Beheshti University of Medical Sciences (SBMU). pH determination

Formulations were diluted 1–10 with water and homogenized with Heidolph homogenizer (RZR 50, Germany), and then the pH of mixture was determined using Hanna Instruments pH meter (PH 211, Romania). Determination of depilation time

Different methods have been used for measurement of efficiency of depilatory formulations. Some researchers have designed and used a depilometer apparatus,5 and some others have studied depilation time on human volunteers or animal models.14 Another method for determination of efficiency of hair removal formulations is measurement of hair tensile strength,1,4 which was employed here. For this purpose, a home-made tensile tester was designed based on mechanical analyzers at constant temperature and/or constant load as described by Brown.16 Briefly, the apparatus is composed of two hooks, between which a single hair is fastened, and a pan connected to the lower hook that holds the load. In each study, a single hair fiber was fixed between two hooks, and the stress was applied using a predetermined load, and the time at which the hair was torn was measured and reported as the “tear resistance time (TRT)”, which is representative of the hair tensile strength. The system was then calibrated using Veet® depilatory cream, applied to 3 cm of the hair shaft and different loads of 2–50 g (Table 1). Results showed a

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. H R Moghimi et al.

linear relationship between load and log time (log TRT) in the range of 3–20 g (P < 0.05, R2 = 0.94), which correlates well with relationship between stress (load) for a given strain and time, reported by Wickett and Mermelstein for determination of the effects of some conditions (such as pH and oxidative material) on the effects of depilatory formulations.4 Based on the results (Table 1), a constant load of 6 g, which provides a TRT of around 5–6 min (the depilation time mentioned on the label of Veet®), was chosen for the rest of the experiments. The system was then validated and showed a good reproducibility (no statistical difference between data collected for five different days, P > 0.05) and acceptable precision (Relative Standard Deviation, RSD, below 5%). Besides, it has been shown by Wickett and Mermelstein that in vitro tensile measurements can reasonably predict the depilation time in vivo.4 Effect of hydration time and hydration temperature on depilation time

For studying the effects of hydration time and temperature, hair samples were first hydrated by soaking in distilled water at ambient temperature (23 ± 2 °C) for 5 min, 10 min, 1 h, and 24 h and at 37, 60, and 95 °C (boiling water) for 5 and 10 min. The TRTs of treated samples were then measured using Veet® depilatory cream at ambient temperature. Effects of penetration enhancers on depilation time

Enhancer pretreatment To study the effects of hydrophilic enhancers, hair samples were pretreated by soaking in 75% and 96%

Table 1 Effect of weight load on tear resistance time (min) of hair samples, treated with Veet® depilatory cream at ambient temperature. Data are mean ± SD (n) Weight (g)

Subject 1

Subject 2

50* 20 10 6 5 3 2.75† 2.5† 2†

– 1.52 2.83 5.37 6.27 9.70 – – –

– 1.33 2.65 5.25 6.73 7.93 – – –

(1) ± 0.37 (3) ± 0.42 (3) ± 0.42 (3) (1)

(1) ± 0.27 (3) ± 0.57 (3) ± 0.42 (3) (1)

*Hair was torn in less than 10 sec. † Hair was not torn even after 10 min.

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hydroethanolic solutions, 0.9% and 1.8% (w/v) NaCl aqueous solutions, 0.0005%, 0.5%, and 1% (w/v) aqueous solutions of sodium dodecyl sulfate, DMSO 60% (w/v) solution in water, and 0.005, 5, 10, 20, and 30% (w/v) solutions of urea in water, all separately and for two time length of 5 and 10 min. For lipophilic enhancers, hair samples were pretreated by soaking for 10 min in 10% ethanolic solution of peppermint oil, 10% ethanolic solution of orange (terpenless) oil, and also pure peppermint and pure orange (terpenless) oil. After enhancer pretreatment, TRTs were measured using Veet® depilatory cream at ambient temperature. All of these enhancers are safe and use as an enhancer in the skin preparations.17 Enhancer-containing formulations Calcium thioglycolate creams containing 30% (w/w) DMSO or 13% (w/w) ethanol were applied to 3 cm of hair loaded on the apparatus, and TRT was measured at ambient temperature. Effect of environmental temperature

To study the effect of environmental temperature (surrounding temperature), all the apparatus and equipments were placed in an oven at 37 ± 1 °C, and TRTs of hair samples were measured using Veet®. Statistics

Out layer data have been determined through use of Dixon’s Q-test. The results were analyzed statistically with STATISTICA software (StatSoft Inc., Tulsa, OK, USA (2001), Version 6), using two-way ANOVA and Post hoc test. The level of significance was considered 0.05. Decrease in TRT is represented here as enhancement ratio: TRT in control group divided by TRT after enhancer treatment.

Results and discussion Effect of hydration time and water temperature on TRT

Hydration is one of the well-known approaches to improve transdermal delivery of chemicals.17 It has also been suggested that increased depilatory effect by urea treatment is due to increased hydration of hair shaft.1 The present investigation, however, shows that hydration in distilled water at ambient temperature even up to 24 h and at higher temperatures of 37 and 60 °C cannot accelerate the depilation action (P > 0.1, Table 2). But hydration in boiling water reduced TRT

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Table 2 Effect of hydration temperatures on depilatory effect (min) of Veet®. Data are mean ± SD (n). Tear resistance time (min) Hydration time (min)

Hydration temperature

0 (control) 5 10 5 10 5 10 5

AT* † AT † AT 37°C 37°C 60°C 60°C (Boiling water) 95°C (Boiling water) 95°C

10

Subject 1 6.05 5.07 5.53 5.58 5.37 5.50 5.20 4.22

± ± ± ± ± ± ± ±

0.17 0.33 0.30 0.23 0.23 0.23 0.23 0.23

Subject 2 (28) (8) (10) (10) (10) (10) (10) (10)

4.21 ± 0.23 (10)

5.45 5.67 5.12 5.38 5.52 5.63 5.35 4.23

± ± ± ± ± ± ± ±

0.12 0.30 0.27 0.28 0.28 0.28 0.28 0.32

(64) (10) (13) (10) (10) (10) (10) (8)

4.10 ± 0.32 (8)

*Dry control. † Hydrated control.

significantly (P < 0.01) by about 1.5 times (Table 2). In addition, there was no difference between boiling for 5 and 10 min (P > 0.05). It is obvious that boiling water cannot be used in vivo due to its hazards and inconvenience. This experiment was performed here to evaluate the effect of higher temperatures that can affect proteins. Besides, as mechanism of action of some enhancement method is similar to that of temperature (e.g., fluidization),18 this experiment can be used to identify some effective enhancers. This method also might find its application in dehairing hides or other ex vivo hair removing methods. Effect of hydrophilic skin penetration enhancers on TRT

Effects of different hydrophilic molecules that have been shown to act as a skin penetration enhancer either through hydration or effects on skin proteins and lipids, including ethanol, dimethylsulfoxide (DMSO), urea, NaCl, and sodium dodecyl sulfate (SDS) were studied here at ambient temperature. There is not much report on the application of penetration enhancers for improvement of chemicals delivery to hair shaft. Therefore, as stratum corneum and hair show some compositional similarities, it was decided here to use skin penetration enhancers for the same purpose in hair. Results showed that pretreatment with 75% ethanol solution for 5 min can reduce TRT by about 1.5 times from approximately 5.4–3.8 min (P < 0.0001); increase of the pretreatment time to 10 min was not able to cause further reduction in TRT (P > 0.05, Table 3 and Fig. 1). Ninety-six percent aqueous solution of ethanol

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Effect of chemical enhancers on efficacy of depilatories

Table 3 Effect of pretreatment with 75 and 96% ethanolic aqueous solutions and DMSO (as 60% solution in water) on depilatory effect (min) of Veet® at ambient temperature. Data are mean ± SD (n). Tear resistance time (min) Pretreatment time (min)

Treatment

Subject 1

0 (Control)* 5 (Control)† 10 (Control)† 5 10 5 10 5 10

None Water Water Ethanolic 75% Ethanolic 75% Ethanolic 96% Ethanolic 96% DMSO 60% DMSO 60%

6.05 5.06 5.53 3.87 3.78 5.23 5.57 5.15 3.77

± ± ± ± ± ± ± ± ±

0.17 0.33 0.30 0.30 0.30 0.30 0.30 0.28 0.27

Subject 2 (28) (8) (10) (8) (8) (8) (8) (8) (9)

5.45 5.67 5.12 3.65 3.20 5.35 4.58 5.73 3.63

± ± ± ± ± ± ± ± ±

0.12 0.30 0.27 0.32 0.35 0.33 0.33 0.32 0.30

(64) (10) (13) (10) (8) (9) (9) (8) (9)

*Dry control. †Hydrated control.

Figure 1 Enhancement effect of ethanol and DMSO at different concentrations (as solution in water) and treatment times toward depilatory effect of Veet® cream. Data are mean ± SD for two subjects. See Table 3 for detailed data.

was not able to reduce the TRT in none of the conditions. There is no report about the effect of ethanol on hair in the literature, but in the skin, when used at high concentration for a prolonged time, ethanol has been shown to extract stratum corneum lipid.17 It has also been shown that the enhancement effect of ethanol toward permeation of oestradiol19 and salicylate ion (sodium salicylate)20 through human epidermal membrane is concentration-dependent with a parabolic relationship that peaks around 60%, both show that the ethanol at around 90% has lower enhancement effect than around 75%, in good correlation with the present data.

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DMSO is one of the well-studied skin penetration enhancers. The enhancement effect of DMSO is concentration-dependent, and generally solutions containing  60% DMSO show optimum enhancement efficacy.17 Pretreatment with 60% DMSO solution for 5 min did not affect the TRT (P > 0.2). When the pretreatment time was increased to 10 min, TRT was reduced up to 1.8 times (P = 0.0001, Table 3 and Fig. 1). The mechanism of DMSO as transdermal enhancer is complex. It can denature proteins and change the intercellular keratin conformation from a-helical to a b-sheet. Also, it can interact with intercellular lipid domain of the stratum corneum and head groups of some bilayer lipids to change the packing geometry.17 Pretreatment with NaCl solution for 5 and 10 min and even at higher concentration of NaCl does not change TRT significantly (P > 0.1). The highest TRT reduction was found in the case of subject 1 pretreated for 10 min in 1.8% solution of NaCl that was about 15% which again was not statistically significant (P = 0.16). For investigating the effect of pretreatment with SDS, concentrations up to 1% and the pretreatment times up to 10 min were used. The TRT for untreated and pretreated hair samples with water (No SDS) for 5 and 10 min were found to be about 5.64 ± 1.10 (92), 5.41 ± 0.81 (18), and 5.30 ± 0.80 (23) min, respectively; Data are mean ± SD (n) for two subjects. Resistance time for hair samples pretreated for 5 and 10 min with the 1% SDS solution (the highest used concentration) changed to 5.14 ± 0.93 min (n = 16, two subjects) and 5.24 ± 0.72 min (n = 18, two subjects), respectively. According to these results, at SDS concentrations and treatment times used in this investigation, SDS cannot reduce TRT significantly (P > 0.1). Urea is a hydrating agent, which act probably through increasing stratum corneum water content and keratolytic activity.17 Here, the effect of 0, 0.005, 5, 10, 20, and 30% solutions of urea and the pretreatment times of up to 10 min were studied. TRT for untreated samples and pretreated samples for 5 and 10 min with water (no urea) were measured to be 5.64 ± 1.1 (92), 5.41 ± 0.81 (18), and 5.30 ± 0.80 (23) min, respectively; Data are mean ± SD (n) for two subjects. When hair samples were pretreated for 5 and 10 min with 30% urea solution, TRT changed to 5.37 ± 0.51 (9) and 5.31 ± 0.57 (9) min, respectively. These results show that in the condition employed here, urea cannot reduce TRT (P > 0.1). It has been suggested that urea, due to swelling and keratolytic

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effects, might decrease the depilation time.1 This hypothesis is not supported by the present data. Effect of lipophilic skin penetration enhancers (essential oils) on TRT

Essential oils and terpenes are well investigated as skin penetration enhancers.17 In this study, orange terpenless oil and peppermint oil were used as enhancers. Orange terpenless oil, when applied alone or in 10% ethanolic solution, was not able to change the TRT (Table 4 and Fig. 2). It has been shown that d-limonene, which is present in the used orange terpenless oil, shows enhancement effect toward transdermal permeation of some drugs.21,22 Peppermint oil alone was not also able to change the TRT, but its 10% ethanolic solutions for 10 min reduced TRT by about 1.6 times (P < 0.0002, Table 4 and Fig. 2). The used peppermint oil contains limonene, menthone, and cineole, all of

Table 4 Effect of pretreatment with pure and 10% ethanolic solutions of two essential oils on depilatory effect (min) of Veet® at ambient temperature. Data are mean ± SD (n). Tear resistance time (min) Treatment

Subject 1

Control* Peppermint oil-pure Peppermint oil-ethanolic Orange terpenless oil-pure Orange terpenless oil-ethanolic

6.05 5.37 3.28 5.48 5.55

which show enhancement effect toward permeation of drugs through skin, mainly through stratum corneum lipid disruption.21–23 Present data show that peppermint oil alone cannot reduce TRT, but when applied as ethanolic (absolute) solution it can reduce TRT by about 1.5 times. Nevertheless, ethanol (absolute), when added to orange terpenless oil, was not able to show the same results. These data show that the effect is not due to ethanol and might reveal that ethanol improves permeation of components of peppermint oil in the hair shaft. Effect of environmental temperature on TRT

Results showed that increase in the environmental temperature from ambient (23 ± 2 °C) to 37 °C reduces TRT by about 4 times (P = 0.0001) in both subjects; from 6.05 ± 0.15 (28) to 1.5 ± 0.27 (9) in subject 1 and from 5.45 ± 0.10 (64) to 1.30 ± 0.28 (9) in subject 2. This is outstanding and seems that increasing the temperature might increase the rate of thioglycolate reaction with hair1 or cause changes in the hair protein and lipid structures and subsequently improves thioglycolate penetration into hair shafts and therefore reduce the TRT.

Subject 2

Effects of enhancers applied as the cream formulations ± ± ± ± ±

0.17 0.27 0.27 0.27 0.27

(28) (9) (9) (9) (9)

5.45 5.13 3.48 5.4 5.3

± ± ± ± ±

0.12 0.28 0.28 0.28 0.28

(64) (9) (9) (9) (9)

*Dry control.

TRT for creams containing enhancers is shown in Table 5. Results reveal that TRT for calcium thioglycolate cream is greater than the Veet® depilatory cream, which can be due to differences in their formulations and of the effects of salts (potassium salt versus calcium) on depilatory action.1 Calcium thioglycolate cream containing DMSO cannot break the hair even after 1 h. It is suggested that precipitating of protein can hinder the penetration of thioglycolate to the target site.8 So this effect maybe due to DMSO ability to

Table 5 Effects of calcium thioglycolate creams without (base cream) and with penetration enhancers on tear resistance time (min) of hair samples at ambient temperature. Data are mean ± SD (n). Tear resistance time (min)

Figure 2 Enhancement effect of essential oils (pure or as ethanolic solutions) toward depilatory effect of Veet® cream. Data are mean ± SD for two subjects. See Table 4 for detailed data. PO: pure peppermint oil; PO/EtOH: peppermint oil 10% ethanolic solution; OTO: pure orange terpenless oil; OTO/EtOH: orange terpenless oil 10% ethanolic solution.

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Formulation

Subject 1

Subject 2

Base cream (control) DMSO cream Ethanolic cream

28.98 ± 1.07 (9) NT 19.75 ± 1.07 (9)

26.78 ± 1.00 (9) NT 20.18 ± 1.07 (9)

NT: Hairs did not tear after 1 h.

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Effect of chemical enhancers on efficacy of depilatories

denaturate protein. Calcium thioglycolate cream containing ethanol (13%) reduced the TRT in comparison with control (calcium thioglycolate base cream) by about 1.5 times (P < 0.001).

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Therefore, although it is likely that the same results might be found for hair, it is worth to investigate such relationship for hair as well.

Acknowledgments Conclusion The present results show that depilatory effect of thioglycolates, presented here as TRT, can be improved by temperatures manipulation, hydration, and application of penetration enhancers. Among the used enhancers, ethanol, DMSO, and ethanolic solution of peppermint oil showed to be effective. However, the possibility of enhancement of thioglycolate permeation by these penetration enhancers and increase the chance of toxicity by thioglycolates cannot be dismissed and should be considered in formulation optimization. Depilatory creams require high pH values for a reasonable depilation time, usually pHs of up to 12, that is harmful to skin. As pH reduction could increase depilation time, the mentioned penetration enhancers might be useful for compensation of decreased depilatory effect due to reduced pH and may be used to prepare depilatory formulations that work at lower pHs while still show a high efficiency for depilation at a less-irritant environment. In this direction, results of a preliminary study, performed in our laboratory, showed that ethanol is able to compensate for reducing of pH of formulations from 12 to 11.5. This approach is novel, and to the best of our knowledge, there is not such a study reported in the literature. Besides depilatory enhancement, this approach can also be employed for optimization of other hair cosmetics. However, it is necessary to investigate the effect of these enhancers on permeation of thioglycolates through their interaction with skin, which is the subject of another investigation. Our statistical analysis also shows that both individuals and cumulative RSDs are well below 5%. Such low RSDs make data valid for conclusion in this descriptive study. For extrapolation to the whole population, however, it is recommended to perform the same investigation on more individuals. Finally, to the best of our knowledge, there is no report about age-related permeability changes in hair shaft. However, published studies on the effect of age on the permeability of the skin have shown that there are no significant differences between skin absorption of water over the range of 13–76 years old24 or permeation of hydrophilic and lipophilic drugs over 17–89 years old25 in both males and females.

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This work was a part of PharmD thesis of B. Jamali and was financially supported by Pharmaceutical Sciences Research Center (SBMU), Tehran, Iran.

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