EFFECT OF A UREA-BASED COMPOUNDED MOISTURIZER 211 et al. (21) also confi rmed our results, where 5% urea-based formulation containing poly- acrylamine C13–14 isoparaffi n showed better moisturizing effect than formulation with- out this excipient. Lower water content of compounded formulation could be another factor which may affect the moisturizing effect of the product. Kim et al. (22) reported better moistening effect after the application of vehicles containing higher water contents. In the indus- trial scale, it is preferred to increase the water content of semisolids as an available and inexpensive ingredient to manage their operating margin. Hence, polyacrylamide C13–14 isoparaffi n Laureth-7 was used to stabilize the fi nished product and prevent any phase separation due to high content of water. At pharmacies, more hydrophilic petrolatum and minimum water are used to inhibit any instability. Dissimilar homogeneity of formula tions is another variation factor. Incorporation of in- gredients in the compounded product is manual, which may cause uneven spread of in- gredients in preparation, leading to insuffi cient occlusion and increasing the TEWL. In addition, the manufacturing company and pharmacist may provide their ingredients from different sources with dissimilar quality, which may interfere with their therapeutic effects. Four hours after single applicati on of moisturizers (where participants were not allowed to wash the treated area), the levels of skin surface lipids were relatively higher in the application site of compounded products. This increase was signifi cant in the group using 10% urea cream. It displays that commercial products are less greasy and leave little residue on skin after 4 h. Less oily formulas probably cause superior spreadability and cosmetic acceptability (6), as the present study approved. Another noteworthy point is the increased skin pH after the 1-week application of both products. It is probably due to high pH of formulations (Table I) because of alkaloid characteristics of urea, affecting skin barrier during repeated applications. The elevated pH in skin decreases lipid processing in SC, disturbs organization of the lipid bilayers, and increases serine protease activity. The mentioned process affects barrier homeostasis and SC cohesion negatively, and consequently aggravates xerosis condition (23–25). The formulations differed in pH. A potential reason is that the source of ingredients such as urea and hydrophilic petrolatum could be different in these two types of prod- ucts. Second, in commercial products, there are benzoic acid esters which reduce the pH of formulation, but this ingredient was not added in compounded products because the pharmacist at pharmacy usually does not add preservative to compounded prod- ucts. However, Danby et al. (26) reported the same effect of two emollient with pH 4.92 and 7.34 on skin pH because the pH-buffering capacity of skin has been reported to be good. We describe a methodological approach to compare compounded and commercial moisturizers. Two commonly prescribed formulations containing similar vehicle and active ingredients were used. To decrease the effect of by-products, a simple formula- tion with limited moisturizing agent and few excipients were selected. The other limitation is the small number of participants and short term of follow-up, despite the fact that the fi ndings were signifi cant. The framework of this study could be ap- plied for comparing more complicated formulations in larger sample sizes to provide better understanding.
JOURNAL OF COSMETIC SCIENCE 212 CONCLUSION Although compounded and commercial urea containing hydrophilic petrolatum have demonstrated decent effects on skin barrier function, commercial formulation led to better improvement on skin hydration and TEWL after a single application, probably because of the infl uence of excipients. Considering this and also the higher acceptability of com- mercial products, the current study did not come up with a suffi cient added value for the pharmacy product relative to commercial one it is recommended to be replaced in simi- lar conditions. Disclosure: This study was approved by the Ethics Committee of Tehran University of Medical Sciences (acceptance code: IR.TUMS.VCR.REC.1398.710, date: 2019. 12.17). It was also registered in the Iranian Register of Clinical Trials (registration code: IRCT20190210042676N9). REFERENCES (1) P. Staubach, S. Salzmann, A. Peveling-Oberhag, V. Weyer, S. Zimmer, G. Gradl, and B. M. Lang, Extemporaneous formulations in Germany-relevance for everyday clinical practice, J. Dtsch. Dermatol. Ges, 16, 567–576 (2018). (2) J. Gudeman, M. Jozwiakowski, J. Chollet, and M. Randell, Potential risks of pharmacy compounding, Drugs R., 13(1), 1–8 (2013). (3) D. L. Elder, A Practical Guide to Contemporary Pharmacy Practice and Compounding, 4th Ed. (Wolters Kluwer Health Press, Philadelphia, PA, 2018) (4) O. Kiseļova, B. Mauriņa, and V. Šidlovska, Analysis of extemporaneous prescriptions prescribed by dermatovenerologists in Latvia and comparison with standardized compounded preparation monographs of Germany and USA, Medicina (Kaunas), 56(1), 29–33 (2020). (5) M. Loden, The clini c al benefi t of moisturizers, J. Eur. Acad. Dermatol. Venereol., 19(6), 672–688 (2005). (6) A. Samadi, S. Ahmad Nasrollahi, M. Maghsoudi Ashtiani, C. Abels, and A. Firooz, Changes in skin barrier function following single and repeated applications of 4 types of moisturizers: a randomized controlled trial, J. Eur. Acad. Dermatol. Venereol., 34(6), e288–e290 (2020). (7) L. Celleno, Topical urea in skincare: a review, Dermatol. Ther., 31(6), e12690 (2018). (8) H. Elliott Campbell , M. Dirk Elston, and C. L. Straughan, A review of the clinical indications, general principles and techniques related to compounding, J. Am. Acad. Dermatol., 83(1), 179–183 (2020). (9) M. Sánchez Regañaa, F. Llambí-Mateosb, M. Salleras-Redonneta, M. Iglesias Sanchoa, H. Collgros Totosausa, and P. Umbert Milleta, Compounding as a current therapeutic option in dermatology, Actas Dermosifi liogr., 104(9), 738–756 (2013). (10) A. Firooz, H. Zartab, B. Sadr, L. N. Bagherpour , A. Masoudi, F. Fanian, Y. Dowlati, A. H. Ehsani, and A. .Samadi, Daytime changes of skin biophysical characteristics: a study of hydration, transepidermal water loss, pH, sebum, elasticity, erythema, and color index on middle eastern skin, Indian J. Dermatol., 61(6), 700–708 (2016). (11) E. H. Mojumdar, Q. D. Pham, D. Topgaard, and E. Sparr, Skin hydration: interplay between molecular dynamics, structure and water uptake in the stratum corneum, Sci. Rep., 7(1), 15712 (2017). (12) M. Pan, G. Heinecke, S. Bernardo, C. Tsui, and J . Levitt, Urea: a comprehensive review of the clinical literature, Dermatol. Online J., 19(11), 20392 (2013). (13) C. Borelli, S. Bielfeldt, S. Borelli, M. Schall e r, and H. C. Korting, Cream or foam in pedal skin care: towards the ideal vehicle for urea used against dry skin, Int. J. Cosmet. Sci., 33(1), 37–43 (2011). (14) V. David, Urea creams in skin conditions: compo s ition and outcomes, Dermatol. Pract., 18(3), 13–15 (2012). (15) C. Albèr, I. Buraczewska-Norin, V. Kocherbitov, S. Saleem, M. Lodén, and J. Engblom, Effects of water activity and low molecular weight humectants on skin permeability and hydration dynamics - a double- blind, randomized and controlled study, Int. J. Cosmet. Sci., 36(5), 412–418 (2014). (16) S. Grether-Beck, I. Felsner, H. Brenden, Z. Kohne, M. Maj o ra, A. Marini, T. Jaenicke, M. Rodriguez- Martin, C. Trullas, M. Hupe, P. M. Elias, and J. Krutmann, Urea uptake enhances barrier function and antimicrobial defense in humans by regulating epidermal gene expression, J. Invest. Dermatol., 132, 1561–1572 (2012).
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