{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T11:42:18Z","timestamp":1777894938917,"version":"3.51.4"},"reference-count":73,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,3,30]],"date-time":"2021-03-30T00:00:00Z","timestamp":1617062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>The by-products of olive oil industry are a major ecological issue due to their phenolic content, highly toxic organic load, and low pH. However, they can be recovered and reused, since their components have antioxidant, anti-inflammatory, and photoprotector properties. In this work, oil-in-water creams containing three different olive oil industry by-products extracts were produced without the use of organic solvents. First, the extracts were thoroughly characterized in vitro for cytotoxicity, inhibition of skin enzymes, and antioxidant and photoprotection capacities. Safety studies were then performed, including ocular and skin irritation tests, ecotoxicity evaluation, and in vivo Human Repeat Insult Patch Test. The results obtained in this initial characterization supported the incorporation of the extracts in the cream formulations. After preparation, the creams were characterized for their organoleptic, physicochemical, droplet size and rheological properties, and microbial contamination. The results showed that all formulations were semi-solid creams, with stable pH, compatible with the skin, without microbial contamination, and with the expected droplet size range. The rheological analysis showed shear-thinning behavior with yield stress, with the viscosity decreasing with increasing shear rate. The oscillatory results suggest that the creams have a strong network structure, being easily rubbed into the skin. Finally, compatibility, acceptability and antioxidant efficacy were evaluated in vivo, in human volunteers. No adverse reactions were observed after application of the formulations on skin and the cream with the highest concentrations of phenolic compounds showed the highest antioxidant efficiency. In conclusion, the results suggest that olive oil industry by-products extracts have valuable properties that favor their re-use in the cosmetic industry. The example presented here showed their successful incorporation into creams and their impact in these formulations\u2019 appearance, pH, and rheological performance, as well as their in vivo compatibility with skin and antioxidant efficiency.<\/jats:p>","DOI":"10.3390\/pharmaceutics13040465","type":"journal-article","created":{"date-parts":[[2021,3,30]],"date-time":"2021-03-30T09:57:04Z","timestamp":1617098224000},"page":"465","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Investigations of Olive Oil Industry By-Products Extracts with Potential Skin Benefits in Topical Formulations"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6133-9943","authenticated-orcid":false,"given":"Andreia","family":"Nunes","sequence":"first","affiliation":[{"name":"Research Institute for Medicine (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6799-2740","authenticated-orcid":false,"given":"L\u00eddia","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Research Institute for Medicine (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5523-5622","authenticated-orcid":false,"given":"Joana","family":"Marto","sequence":"additional","affiliation":[{"name":"Research Institute for Medicine (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4822-3249","authenticated-orcid":false,"given":"Ana Margarida","family":"Martins","sequence":"additional","affiliation":[{"name":"Research Institute for Medicine (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal"}]},{"given":"Alexandra N.","family":"Silva","sequence":"additional","affiliation":[{"name":"ADEIM, Laborat\u00f3rio de Controlo Microbiol\u00f3gico, 1649-003 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5723-0750","authenticated-orcid":false,"given":"Pedro","family":"Pinto","sequence":"additional","affiliation":[{"name":"Research Institute for Medicine (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal"},{"name":"PhDtrials, Avenida Maria Helena Vieira da Silva, n\u00b0 24 A, 1750-182 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3818-6256","authenticated-orcid":false,"given":"Marta","family":"Martins","sequence":"additional","affiliation":[{"name":"Marine and Environmental Sciences Centre (MARE), NOVA School of Science and Technology (FCT NOVA), Campus da Caparica, 2829-516 Caparica, Portugal"}]},{"given":"Carmo","family":"Fraga","sequence":"additional","affiliation":[{"name":"Sovena Portugal\u2014Consumer Goods, S.A., Rua Dr. Ant\u00f3nio Borges n\u00b02, Edif\u00edcio Arquiparque 2-3\u00b0 Andar, 1495-131 Alg\u00e9s, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2429-7991","authenticated-orcid":false,"given":"Helena Margarida","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Research Institute for Medicine (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1111\/j.1753-4887.2010.00278.x","article-title":"Hydroxytyrosol: From laboratory investigations to future clinical trials","volume":"68","author":"Quiles","year":"2010","journal-title":"Nutr. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Romani, A., Ieri, F., Urciuoli, S., Noce, A., Marrone, G., Nediani, C., and Bernini, R. (2019). Health effects of phenolic compounds found in extra-virgin olive oil, by-products, and leaf of Olea Europaea L.. Nutrients, 11.","DOI":"10.3390\/nu11081776"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.ijfoodmicro.2017.03.019","article-title":"Antimicrobial activity of Olea europaea Linn\u00e9 extracts and their applicability as natural food preservative agents","volume":"251","author":"Thielmann","year":"2017","journal-title":"Int. J. Food Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"109683","DOI":"10.1016\/j.foodres.2020.109683","article-title":"Valorization of by-products from olive oil industry and added-value applications for innovative functional foods","volume":"137","author":"Astray","year":"2020","journal-title":"Food Res. Int."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1016\/j.procbio.2013.07.010","article-title":"Olive mill wastes: Biochemical characterizations and valorization strategies","volume":"48","author":"Dermeche","year":"2013","journal-title":"Process. Biochem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.3390\/12051153","article-title":"Phenolic compounds and antimicrobial activity of olive (Olea europaea L. Cv. Cobran\u00e7osa) leaves","volume":"12","author":"Pereira","year":"2007","journal-title":"Molecules"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"73","DOI":"10.2166\/wst.2016.181","article-title":"Innovative method for recovery and valorization of hydroxytyrosol from olive mill wastewaters","volume":"74","author":"Bonetti","year":"2016","journal-title":"Water Sci. Technol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.indcrop.2015.03.027","article-title":"Olive by-products: Challenge application in cosmetic industry","volume":"70","author":"Rodrigues","year":"2015","journal-title":"Ind. Crop. Prod."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4","DOI":"10.4172\/2252-5211.1000161","article-title":"Polyphenols extracted from olive mill wastewater exert a strong antioxidant effect in human neutrophils","volume":"4","author":"Bedouhene","year":"2014","journal-title":"Int. J. Waste Resour."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.tifs.2015.06.010","article-title":"Phenolic compounds from olive mill wastes: Health effects, analytical approach and application as food antioxidants","volume":"45","author":"Pimentel","year":"2015","journal-title":"Trends Food Sci. Technol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.tifs.2014.12.009","article-title":"Bioactive profile, dehydration, extraction and application of the bioactive components of olive leaves","volume":"42","author":"Rahmanian","year":"2015","journal-title":"Trends Food Sci. Technol."},{"key":"ref_12","first-page":"128","article-title":"Hydroxytyrosol and oleuropein from olive leaves: Potent anti-inflammatory and analgesic activities","volume":"9","author":"Haloui","year":"2011","journal-title":"J. Food Agric. Environ."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2011","DOI":"10.1021\/jf103881b","article-title":"Chemical and cellular antioxidant activity of phytochemicals purified from olive mill waste waters","volume":"59","author":"Angelino","year":"2011","journal-title":"J. Agric. Food Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.jphotobiol.2019.03.003","article-title":"Photoprotection assessment of olive (Olea europaea L.) leaves extract standardized to oleuropein: In vitro and in silico approach for improved sunscreens","volume":"193","author":"Silva","year":"2019","journal-title":"J. Photochem. Photobiol. B Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.eti.2017.12.002","article-title":"Phenols from olive mill wastewater and other natural antioxidants as UV filters in sunscreens","volume":"9","author":"Galanakis","year":"2018","journal-title":"Environ. Technol. Innov."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.foodchem.2009.12.013","article-title":"Phenolic compounds in olive oil and olive pomace from Cilento (Campania, Italy) and their antioxidant activity","volume":"121","author":"Cioffi","year":"2010","journal-title":"Food Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/S0367-326X(02)00173-9","article-title":"Antioxidative and radical scavenging effects of olive cake extract","volume":"73","author":"Amro","year":"2002","journal-title":"Fitoterapia"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3751","DOI":"10.1016\/j.biortech.2009.12.052","article-title":"Antioxidant and antimicrobial activities of individual and combined phenolics in Olea europaea leaf extract","volume":"101","author":"Lee","year":"2010","journal-title":"Bioresour. Technol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"7609","DOI":"10.1021\/jf0706934","article-title":"New insights into controversies on the antioxidant potential of the olive oil antioxidant hydroxytyrosol","volume":"55","author":"Rietjens","year":"2007","journal-title":"J. Agric. Food Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2003","DOI":"10.1016\/j.bcp.2004.06.023","article-title":"Antioxidant effect of hydroxytyrosol, a polyphenol from olive oil: Scavenging of hydrogen peroxide but not superoxide anion produced by human neutrophils","volume":"68","author":"Driss","year":"2004","journal-title":"Biochem. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e1900019","DOI":"10.1002\/mnfr.201900019","article-title":"Olive-oil-derived polyphenols effectively attenuate inflammatory responses of human keratinocytes by interfering with the NF-\u03baB pathway","volume":"63","author":"Redhu","year":"2019","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_22","first-page":"382","article-title":"TNF-\u03b1 and IL-10 modulation induced by polyphenols extracted by olive pomace in a mouse model of paw inflammation","volume":"51","author":"Carito","year":"2015","journal-title":"Ann. Ist. Super. Sanit\u00e0"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1007\/s00210-005-1078-y","article-title":"Hydroxytyrosol, a phenolic compound from virgin olive oil, prevents macrophage activation","volume":"371","author":"Maiuri","year":"2005","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1890","DOI":"10.1055\/s-0031-1280022","article-title":"Hydroxytyrosol is the major anti-inflammatory compound in aqueous olive extracts and impairs cytokine and chemokine production in macrophages","volume":"77","author":"Richard","year":"2011","journal-title":"Planta Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1801","DOI":"10.1292\/jvms.18-0250","article-title":"Anti-inflammatory effects of olive-derived hydroxytyrosol on lipopolysaccharide-induced inflammation in RAW264.7 cell","volume":"80","author":"Yonezawa","year":"2018","journal-title":"J. Vet. Med. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s41702-018-0031-x","article-title":"Anti-inflammatory and anti-aging effects of hydroxytyrosol on human dermal fibroblasts (HDFs)","volume":"2","author":"Jeon","year":"2018","journal-title":"Biomed. Dermatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1007\/s10787-017-0367-7","article-title":"Oleuropein and hydroxytyrosol inhibit the N-formyl-methionyl-leucyl-phenylalanine-induced neutrophil degranulation and chemotaxis via AKT, p38, and ERK1\/2 MAP-Kinase inhibition","volume":"25","author":"Bedouhene","year":"2017","journal-title":"Inflammopharmacology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1002\/ptr.2686","article-title":"Effects of hydroxytyrosol-20 on carrageenan- induced acute inflammation and hyperalgesia in rats","volume":"23","author":"Gong","year":"2009","journal-title":"Phytother. Res."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Fuccelli, R., Fabiani, R., and Rosignoli, P. (2018). Hydroxytyrosol exerts anti-inflammatory and anti-oxidant activities in a mouse model of systemic inflammation. Molecules, 23.","DOI":"10.3390\/molecules23123212"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"9065","DOI":"10.1002\/jcp.27584","article-title":"Hydroxytyrosol from olive fruits prevents blue-light-induced damage in human keratinocytes and fibroblasts","volume":"234","author":"Avola","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1002\/ptr.3048","article-title":"Effects of olive leaf extract and its main component oleuroepin on acute ultraviolet B irradiation-induced skin changes in C57BL\/6J mice","volume":"24","author":"Sumiyoshi","year":"2010","journal-title":"Phytother. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jphotobiol.2014.09.004","article-title":"Antioxidants in the prevention of UVB-induced keratynocyte apoptosis","volume":"141","author":"Salucci","year":"2014","journal-title":"J. Photochem. Photobiol. B Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1016\/j.freeradbiomed.2004.12.015","article-title":"Hydroxytyrosol, a natural antioxidant from olive oil, prevents protein damage induced by long-wave ultraviolet radiation in melanoma cells","volume":"38","author":"Ingrosso","year":"2005","journal-title":"Free Radic. Biol. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1002\/ptr.2943","article-title":"The protective effects of hydroxytyrosol against UVB-induced DNA damage in HaCaT cells","volume":"24","author":"Guo","year":"2010","journal-title":"Phytother. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.jdermsci.2015.07.002","article-title":"Tyrosol prevents apoptosis in irradiated keratinocytes","volume":"80","author":"Salucci","year":"2015","journal-title":"J. Dermatol. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.phanu.2016.10.002","article-title":"An olive polyphenol-based nutraceutical improves cutaneous manifestations of psoriasis in humans","volume":"4","author":"Visioli","year":"2016","journal-title":"PharmaNutrition"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1662","DOI":"10.1111\/jocd.13457","article-title":"Efficacy of olive leaf extract\u2013containing cream for facial rejuvenation: A pilot study","volume":"19","author":"Wanitphakdeedecha","year":"2020","journal-title":"J. Cosmet. Dermatol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.indcrop.2017.09.058","article-title":"Implementation of phenols recovered from olive mill wastewater as UV booster in cosmetics","volume":"111","author":"Galanakis","year":"2018","journal-title":"Ind. Crop. Prod."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.ijpharm.2013.01.024","article-title":"Self-assembled polymeric nanoparticles for percutaneous co-delivery of hydrocortisone\/hydroxytyrosol: An ex vivo and in vivo study using an NC\/Nga mouse model","volume":"444","author":"Hussain","year":"2013","journal-title":"Int. J. Pharm."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1007\/s13346-017-0439-7","article-title":"Potential treatment of atopic dermatitis: Tolerability and safety of cream containing nanoparticles loaded with hydrocortisone and hydroxytyrosol in human subjects","volume":"9","author":"Siddique","year":"2019","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_41","unstructured":"Sakamoto, K., Lochhead, R.Y., Maibach, H.I., and Yamashita, Y. (2017). Cosmetic Science and Technology: Theoretical Principles and Applications, Elsevier. [1st ed.]."},{"key":"ref_42","unstructured":"Souto, E.B., and Lopes, C.M. (2011). Microemuls\u00f5es e nanoemuls\u00f5es. Novas Formas Farmac\u00eauticas para Administra\u00e7\u00e3o de F\u00e1rmacos, Edi\u00e7\u00f5es Universidade Fernando Pessoa."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Nunes, A., Marto, J., Gon\u00e7alves, L.M., Sim\u00f5es, S., F\u00e9lix, R., Ascenso, A., Lopes, F., and Ribeiro, H.M. (2020). Novel and modified neutrophil elastase inhibitor loaded in topical formulations for psoriasis management. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12040358"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/j.ejps.2011.09.017","article-title":"Lipid nanoparticles containing oryzalin for the treatment of leishmaniasis","volume":"45","author":"Lopes","year":"2012","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Roda, G., Marinello, C., Grassi, A., Picozzi, C., Aldini, G., Carini, M., and Regazzoni, L. (2019). Ripe and raw Pu-Erh tea: LC-MS profiling, antioxidant capacity and enzyme inhibition activities of aqueous and hydro-alcoholic extracts. Molecules, 24.","DOI":"10.3390\/molecules24030473"},{"key":"ref_46","unstructured":"(2020, August 29). Sigma Aldrich. Available online: https:\/\/www.sigmaaldrich.com\/technical-documents\/protocols\/biology\/enzymatic-assay-of-hyaluronidase.html."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1006\/niox.1996.0113","article-title":"Dichlorodihydrofluorescein and dihydrorhodamine 123 are sensitive indicators of peroxynitrite in vitro: Implications for intracellular measurement of reactive nitrogen and oxygen species","volume":"1","author":"Crow","year":"1997","journal-title":"Nitric Oxide"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1007\/s00216-006-0366-9","article-title":"Recent advances in fluorescent probes for the detection of reactive oxygen species","volume":"386","author":"Soh","year":"2006","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1016\/j.freeradbiomed.2007.06.026","article-title":"Fluorescent and luminescent probes for measurement of oxidative and nitrosative species in cells and tissues: Progress, pitfalls, and prospects","volume":"43","author":"Wardman","year":"2007","journal-title":"Free Radic. Biol. Med."},{"key":"ref_50","first-page":"121","article-title":"Correla\u00e7\u00e3o entre a determina\u00e7\u00e3o do fator de prote\u00e7\u00e3o solar em seres humanos e por espectrofotometria","volume":"61","author":"Mansur","year":"1986","journal-title":"An. Bras. Dermatol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.indcrop.2015.11.033","article-title":"The green generation of sunscreens: Using coffee industrial sub-products","volume":"80","author":"Marto","year":"2016","journal-title":"Ind. Crop. Prod."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1016\/j.indcrop.2017.09.033","article-title":"Cynara scolymus L.: A promising Mediterranean extract for topical anti-aging prevention","volume":"109","author":"Marques","year":"2017","journal-title":"Ind. Crop. Prod."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1590\/S1516-93322004000300014","article-title":"Determination of sun protection factor (SPF) of sunscreens by ultraviolet spectrophotometry","volume":"40","author":"Dutra","year":"2004","journal-title":"Rev. Bras. Cienc. Farm. J. Pharm. Sci."},{"key":"ref_54","unstructured":"EpiSkin (2017). DB-ALM Protocol n\u00b0 190: SkinEthic TM HCE Eye Irritation Test Solid (EITL), OECD Test Guideline No. 492 n.d., EpiSkin."},{"key":"ref_55","unstructured":"EpiSkin (2012). DB-ALM Protocol n\u00b0 131: EpiSkinTM Skin Irritation Test, OECD Test Guideline No. 439 n.d., EpiSkin."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Couto, J., Figueirinha, A., Batista, M.T., Paranhos, A., Nunes, C., Gon\u00e7alves, L.M., Marto, J., Fitas, M., Pinto, P., and Ribeiro, H.M. (2020). Fragaria vesca L. Extract: A promising cosmetic ingredient with antioxidant properties. Antioxidants, 9.","DOI":"10.3390\/antiox9020154"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1111\/j.1467-2494.2006.00344.x","article-title":"Natural skin surface pH is on average below 5, which is beneficial for its resident flora","volume":"28","author":"Lambers","year":"2006","journal-title":"Int. J. Cosmet. Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.ijpharm.2017.05.005","article-title":"Microemulsion utility in pharmaceuticals: Implications for multi-drug delivery","volume":"526","author":"Callender","year":"2017","journal-title":"Int. J. Pharm."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Tadros, T.F. (2016). Emulsions: Formation, Stability, Industrial Applications, Gruyter Graduate.","DOI":"10.1515\/9783110452242"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"229","DOI":"10.3390\/antiox3020229","article-title":"Antioxidant activity and thermal stability of oleuropein and related phenolic compounds of olive leaf extract after separation and concentration by salting-out-assisted cloud point extraction","volume":"3","author":"Stamatopoulos","year":"2014","journal-title":"Antioxidants"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1016\/j.foodchem.2007.07.004","article-title":"Rheological behaviour of emulsions of avocado and watermelon oils during storage","volume":"106","author":"Logaraj","year":"2008","journal-title":"Food Chem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.colsurfa.2013.01.003","article-title":"Rheological and textural characterization of cosmetic emulsions containing natural and synthetic polymers: Relationships between both data","volume":"421","author":"Gilbert","year":"2013","journal-title":"Colloids Surf. A Physicochem. Eng. Asp."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.biotri.2018.09.003","article-title":"Spreading behavior of cosmetic emulsions: Impact of the oil phase","volume":"16","author":"Gore","year":"2018","journal-title":"Biotribology"},{"key":"ref_64","unstructured":"Malvern Instruments (2015). Understanding Yield Stress Measurements, Malvern Instruments Limited."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/0021-9797(83)90323-5","article-title":"Rheology of foams and highly concentrated emulsions. I -Elastic properties and yield stress of a cylindrical model system","volume":"91","author":"Princen","year":"1983","journal-title":"J. Colloid Interface Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/0021-9797(89)90396-2","article-title":"Rheology of foams and highly concentrated emulsions. IV\u2013An experimental study of the shear viscosity and yield stress of concentrated emulsions","volume":"128","author":"Princen","year":"1989","journal-title":"J. Colloid Interface Sci."},{"key":"ref_67","unstructured":"Chen, T. (2000). Rheological Techniques for Yield Stress Analysis, TA Instruments."},{"key":"ref_68","unstructured":"Barnes, H.A. (2000). A Handbook of Elementary Rheology, University of Wales Institute of Non-Newtonian Fluid Mechanics."},{"key":"ref_69","unstructured":"Malvern Instruments (2016). A Basic Introduction to Rheology, Malvern Instruments Limited."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.ejpb.2004.04.009","article-title":"Liquid and semisolid SLNTM dispersions for topical application: Rheological characterization","volume":"58","author":"Lippacher","year":"2004","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_71","first-page":"1548","article-title":"Emulsions and microemulsions","volume":"3","author":"Eccleston","year":"2007","journal-title":"Encycl. Pharm. Technol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1111\/j.0412-5463.2004.00190.x","article-title":"Structure and rheology of semisolid o\/w creams containing cetyl alcohol\/non-ionic surfactant mixed emulsifier and different polymers","volume":"26","author":"Ribeiro","year":"2004","journal-title":"Int. J. Cosmet. Sci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"417","DOI":"10.3109\/10837450.2013.788516","article-title":"Cold processed oil-in-water emulsions for dermatological purpose: Formulation design and structure analysis","volume":"19","author":"Raposo","year":"2014","journal-title":"Pharm. Dev. Technol."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/13\/4\/465\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:25:42Z","timestamp":1760361942000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/13\/4\/465"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,30]]},"references-count":73,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,4]]}},"alternative-id":["pharmaceutics13040465"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics13040465","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,30]]}}}