{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T16:57:00Z","timestamp":1779296220978,"version":"3.51.4"},"reference-count":44,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T00:00:00Z","timestamp":1763683200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background: Natural alternatives are becoming more popular as a result of health risks associated with synthetic preservatives in pharmaceuticals. Because of its antibacterial properties, Psidium guajava (L.) leaf extract is a practical choice for sustainable preservation. Objectives: The aim of this research is to evaluate the efficacy of Psidium guajava (L.) leaf extract as a 10% (w\/w) natural preservative in five different base formulations: creams (clotrimazole cream, permethrin cream, and gentamicin cream) and gels (indomethacin emulgel and ibuprofen gel). Methods: Over the course of 28 days, antimicrobial activity against Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, Aspergillus brasiliensis, and Candida albicans was evaluated. In accordance with USP\/BP guidelines, three months of accelerated conditions (40 \u00b1 2 \u00b0C\/75% \u00b1 5% RH) were used to assess chemical, physical, and microbiological stability. The stability of the active component was examined using HPLC. Results: Our findings showed that the extract completely inhibited the growth of tested bacterial species in clotrimazole cream, permethrin cream, gentamicin cream, and indomethacin emulgel, demonstrating significant antibacterial activity across all formulations. However, the antifungal activity was restricted. The preservation effectiveness criterion (bacterial\/yeast counts &lt; 10 CFU, mold &lt; 20 CFU) was only fulfilled by ibuprofen gel and clotrimazole cream. Although there were color changes, stability tests verified that the active components such as ibuprofen (reduced from 97.5% to 92%) and clotrimazole (reduced from 99.9% to 95%) decomposed minimally and had acceptable physical characteristics. Particularly against fungus, the extract was surpassed by chemical preservatives (methyl\/propyl paraben). Conclusions: Certain semi-solid pharmaceuticals can benefit from the stability and antimicrobial protection provided by guava leaf extract, a natural preservative. The weak antifungal activity of the guava leaf extract emphasizes the necessity for specific improvements in the formulation.<\/jats:p>","DOI":"10.3390\/antibiotics14121176","type":"journal-article","created":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T08:59:46Z","timestamp":1763715586000},"page":"1176","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Guava Leaf Extract as a Sustainable Preservative Alternative in Semi-Solid Pharmaceuticals: Efficacy and Stability Assessment"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8410-3212","authenticated-orcid":false,"given":"Hamada","family":"Imtara","sequence":"first","affiliation":[{"name":"Department of Biology and Biochemistry, Faculty of Medicine, Arab American University, Ramallah P600, Palestine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad","family":"Atiya","sequence":"additional","affiliation":[{"name":"Chemistry Department, Faculty of Science and Technology, Al-Quds University, Jerusalem P.O. Box 20002, Palestine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5980-0772","authenticated-orcid":false,"given":"Michel","family":"Hanania","sequence":"additional","affiliation":[{"name":"Chemistry Department, Faculty of Science and Technology, Bethlehem University, Bethlehem 00970, Palestine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3023-6909","authenticated-orcid":false,"given":"Jehad","family":"Abbadi","sequence":"additional","affiliation":[{"name":"Biology Department, Faculty of Science and Technology, Al-Quds University, Jerusalem P.O. Box 20002, Palestine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6356-6891","authenticated-orcid":false,"given":"Samer","family":"Mudalal","sequence":"additional","affiliation":[{"name":"Nutrition and Food Technology Program, Department of Agricultural Engineering, Faculty of Veterinary Medicine and Agricultural Engineering, An-Najah National University, Nablus P.O. Box 7, Palestine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9341-6993","authenticated-orcid":false,"given":"Fuad","family":"Al-Rimawi","sequence":"additional","affiliation":[{"name":"Chemistry Department, Faculty of Science and Technology, Al-Quds University, Jerusalem P.O. Box 20002, Palestine"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.9734\/ajocs\/2019\/v6i419003","article-title":"Simultaneous estimation of aspirin, atorvastatin calcium and clopidogrel bisulphate in a combined dosage form by RP-HPLC","volume":"6","author":"Yadav","year":"2019","journal-title":"AJOCS"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"446","DOI":"10.12968\/bjha.2021.15.9.446","article-title":"The skin: Largest organ of the body","volume":"15","author":"Peate","year":"2021","journal-title":"Br. J. Healthc. Assist."},{"key":"ref_3","unstructured":"Hamblin, M.R., Avci, P., and Prow, T.W. (2016). Anatomy and function of the skin. Nanoscience in Dermatology, Academic Press."},{"key":"ref_4","first-page":"390","article-title":"Anatomy, histology and immunohistochemistry of normal human skin","volume":"12","author":"Kanitakis","year":"2002","journal-title":"Eur. J. Dermatol."},{"key":"ref_5","unstructured":"Tabor, A., and Blair, R.M. (2009). Structure and function of the skin. Nutritional Cosmetics: Beauty from Within, William Andrew Publishing."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Cao, C., Xiao, Z., Wu, Y., and Ge, C. (2020). Diet and skin aging\u2014From the perspective of food nutrition. Nutrients, 12.","DOI":"10.3390\/nu12030870"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"135","DOI":"10.2174\/1871526510808030135","article-title":"The role of antimicrobial peptides in human skin and in skin infectious diseases","volume":"8","author":"Schittek","year":"2008","journal-title":"Infect. Disord. Drug Targets"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1111\/j.1365-2133.2008.08437.x","article-title":"Skin microbiota: A source of disease or defence?","volume":"158","author":"Cogen","year":"2008","journal-title":"Br. J. Dermatol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Scheinfeld, N. (2014). Topical treatments of skin pain: A general review with a focus on hidradenitis suppurativa with topical agents. Dermatol. Online J., 20.","DOI":"10.5070\/D3207023131"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.ejps.2015.12.018","article-title":"Pharmaceutical excipients\u2014Quality, regulatory and biopharmaceutical considerations","volume":"87","author":"Elder","year":"2016","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1016\/j.crci.2016.06.004","article-title":"Development of a natural ingredient\u2014Natural preservative: A case study","volume":"19","author":"Kerdudo","year":"2016","journal-title":"C. R. Chim."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1002\/jps.2600500409","article-title":"Potentiation of preservatives (parabens) in pharmaceutical formulations by low concentrations of propylene glycol","volume":"50","author":"Prickett","year":"1961","journal-title":"J. Pharm. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.mce.2018.03.014","article-title":"Parabens and their effects on the endocrine system","volume":"474","author":"Nowak","year":"2018","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1007\/s12595-021-00418-x","article-title":"An overview of endocrine disrupting chemical paraben and search for an alternative\u2014A review","volume":"74","author":"Mitra","year":"2021","journal-title":"Proc. Zool. Soc."},{"key":"ref_15","first-page":"2496","article-title":"Artificial preservatives and their harmful effects: Looking toward nature for safer alternatives","volume":"4","author":"Anand","year":"2013","journal-title":"Int. J. Pharm. Sci. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1111\/j.1541-4337.2011.00169.x","article-title":"Flower extracts and their essential oils as potential antimicrobial agents for food uses and pharmaceutical applications","volume":"11","author":"Voon","year":"2012","journal-title":"Compr. Rev. Food Sci. Food Saf."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Al-Rimawi, F., Sbeih, M., Amayreh, M., Rahhal, B., and Mudalal, S. (2024). Evaluation of the antibacterial and antifungal properties of oleuropein, olea Europea leaf extract, and thymus vulgaris oil. BMC Complement. Med. Ther., 24.","DOI":"10.1186\/s12906-024-04596-x"},{"key":"ref_18","first-page":"3577","article-title":"An update of pharmacological activity of Psidium guajava in the management of various disorders","volume":"3","author":"Rishika","year":"2012","journal-title":"World J. Pharm. Res."},{"key":"ref_19","first-page":"65","article-title":"Chemical composition, antioxidant and antimicrobial activities of Moroccan species of Psidium guajava extracts","volume":"73","author":"Lahlou","year":"2022","journal-title":"Rocz. Panstw. Zakl. Hig."},{"key":"ref_20","first-page":"1934578X221095349","article-title":"Impact of different drying temperatures on in vitro antioxidant and antidiabetic activities and phenolic compounds of wild guava leaves collected in the central highland of Vietnam","volume":"17","author":"Nguyen","year":"2022","journal-title":"Nat. Prod. Commun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"226","DOI":"10.4103\/0975-7406.80776","article-title":"In vitro antimicrobial activity of methanolic leaf extract of Psidium guajava L.","volume":"3","author":"Dhiman","year":"2011","journal-title":"J. Pharm. Bioallied Sci."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Biswas, B., Rogers, K., McLaughlin, F., Daniels, D., and Yadav, A. (2013). Antimicrobial activities of leaf extracts of guava (Psidium guajava L.) on two gram-negative and gram-positive bacteria. Int. J. Microbiol., 2013.","DOI":"10.1155\/2013\/746165"},{"key":"ref_23","first-page":"2","article-title":"Antioxidant capacity and antimicrobial activity of commercial samples of guava leaves (Psidium guajava)","volume":"9","author":"Melo","year":"2020","journal-title":"J. Med. Act. Plants"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Umar, M., Tomar, M., Amarowicz, R., Saurabh, V., Nair, M.S., Maheshwari, C., Sasi, M., Prajapati, U., Hasan, M., and Singh, S. (2021). Guava (Psidium guajava L.) leaves: Nutritional composition, phytochemical profile, and health-promoting bioactivities. Foods, 10.","DOI":"10.3390\/foods10040752"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1007\/s12088-012-0329-0","article-title":"Essential Oils and Herbal Extracts as Antimicrobial Agents in Cosmetic Emulsion","volume":"53","author":"Herman","year":"2013","journal-title":"Indian J. Microbiol."},{"key":"ref_26","first-page":"177","article-title":"Formulation development, physico-chemical characterization and evaluation of anti-microbial activity of herbal tooth gel","volume":"25","author":"Haque","year":"2014","journal-title":"Int. J. Pharm. Sci. Rev. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"102014","DOI":"10.1016\/j.jsps.2024.102014","article-title":"Evaluation of the effectiveness of natural extract as a substituent for synthetic preservatives and antioxidants in pharmaceutical preparations","volume":"32","author":"Sbeih","year":"2024","journal-title":"Saudi Pharm. J."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Davidova, S., Galabov, A.S., and Satchanska, G. (2024). Antibacterial, antifungal, antiviral activity, and mechanisms of action of plant polyphenols. Microorganisms, 12.","DOI":"10.3390\/microorganisms12122502"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Huynh, H.D., Nargotra, P., Wang, H.-M.D., Shieh, C.-J., Liu, Y.-C., and Kuo, C.-H. (2025). Bioactive compounds from guava leaves (Psidium guajava L.): Characterization, biological activity, synergistic effects, and technological applications. Molecules, 30.","DOI":"10.3390\/molecules30061278"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/S0378-8741(02)00185-X","article-title":"Intestinal anti-spasmodic effect of a phytodrug of Psidium guajava folia in the treatment of acute diarrheic disease","volume":"83","author":"Lozoya","year":"2002","journal-title":"J. Ethnopharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1590\/1519-6984.189089","article-title":"Antibacterial and antiproliferative activities of the fresh leaf essential oil of Psidium guajava L. (Myrtaceae)","volume":"79","author":"Silva","year":"2019","journal-title":"Braz. J. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1016\/j.jksus.2018.07.021","article-title":"Chemical composition and biological activities of the essential oils of Psidium guajava leaf","volume":"31","author":"Weli","year":"2019","journal-title":"J. King Saud Univ. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"20","DOI":"10.22270\/jddt.v10i2.3902","article-title":"Formulation and evaluation of transdermal topical gel of ibuprofen","volume":"10","author":"Kashyap","year":"2020","journal-title":"J. Drug Deliv. Ther."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1208\/s12249-011-9583-4","article-title":"Novel jojoba oil-based emulsion gel formulations for clotrimazole delivery","volume":"12","author":"Shahin","year":"2011","journal-title":"AAPS PharmSciTech"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/S0731-7085(96)02044-4","article-title":"Development and validation of a method to extract and quantitate paromomycin and gentamicin from an Aquaphilic\u00ae cream formulation","volume":"16","author":"Pick","year":"1997","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_36","unstructured":"United States Pharmacopeia (USP) (2020). Chapter <51>: Antimicrobial Effectiveness Testing. USP 43\u2013NF 38, United States Pharmacopeial Convention."},{"key":"ref_37","first-page":"157","article-title":"The effect of various vehicles on in-vivo performance of indomethacin from different topical formulations","volume":"4","author":"Kaleemullah","year":"2015","journal-title":"World J. Pharm. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"355","DOI":"10.4314\/tjpr.v9i4.58928","article-title":"Development and evaluation of ibuprofen transdermal gel formulations","volume":"9","author":"Rasool","year":"2010","journal-title":"Trop. J. Pharm. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"S181","DOI":"10.1007\/BF02494135","article-title":"Determination of methylparaben, propylparaben, clotrimazole and its degradation products in topical cream by RP-HPLC","volume":"56","author":"Solich","year":"2002","journal-title":"Chromatographia"},{"key":"ref_40","first-page":"42","article-title":"Determination of permethrin in pharmaceutical product by gas chromatography","volume":"12","author":"Amin","year":"2017","journal-title":"IOSR-J. Pharm. Biol. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"77","DOI":"10.12928\/pharmaciana.v8i1.7336","article-title":"Formulation and physical stability test of oleanolic acid cream and gel","volume":"8","author":"Kartini","year":"2018","journal-title":"Pharmaciana"},{"key":"ref_42","first-page":"341","article-title":"Antimicrobial preservative effectiveness of natural peptide antibiotics","volume":"62","author":"Kamysz","year":"2005","journal-title":"Postep. Mikrobiol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Sahoury, Y., Naseef, H., Farraj, M., Qurt, M., and El-Khaury, L. (2020). Antimicrobial activity of oleuropine and thyme extracts against selected pathogenic microorganisms and their potential uses as natural preservatives. Int. J. Pharm. Res., 13.","DOI":"10.31838\/ijpr\/2021.13.01.178"},{"key":"ref_44","first-page":"e115266","article-title":"Formulation and physicochemical evaluation of a 3% cream using crude 70% ethanolic extract of Morus alba L. leaves for skin hyperpigmentation","volume":"17","author":"Zakeri","year":"2022","journal-title":"Jundishapur J. Nat. Pharm. Prod."}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/14\/12\/1176\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T09:31:28Z","timestamp":1763717488000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/14\/12\/1176"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,21]]},"references-count":44,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["antibiotics14121176"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics14121176","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,21]]}}}